William Spielman | Michigan State University (original) (raw)
Papers by William Spielman
American Journal of Physiology-Cell Physiology, 1991
We studied the effect of cadmium, verapamil, and quinacrine on the force of contraction (Fp) of i... more We studied the effect of cadmium, verapamil, and quinacrine on the force of contraction (Fp) of isolated, single, field-stimulated bullfrog atrial cells. All agents were applied or removed rapidly (t1/2 approximately 15 ms) to minimize intracellular concentration changes other than intracellular calcium concentration. Two components of twitch force were observed, one blocked by micromolar Cd2+ and the other by millimolar Cd2+. The two contributed about equally to the activation of the twitch. The "cadmium-sensitive" portion of force (that affected by [Cd] less than or equal to 100 microM) had a K1/2 approximately 1 microM, was identical in magnitude to, and not additive with, a "verapamil-sensitive" (10 microM) component of force, was most strongly affected by 50-ms pulses of Cd2+ when they were applied in the mechanical latent period, and was potentiated by catecholamines. The cadmium-insensitive portion of force was abolished by the removal of extracellular cal...
Japanese Journal of Pharmacology, 1990
Annals of Biomedical Engineering, Jun 29, 1983
In contrast to the postocclusive hyperemia of brain, heart, and skeletal muscle, the hemodynamic ... more In contrast to the postocclusive hyperemia of brain, heart, and skeletal muscle, the hemodynamic response of the kidney following renal artery occlusion is highly variable in that both hyperemia and ischemia have been reported. The present study evaluates the factors influencing the renal response to complete renal artery occlusion (5–60 sec) in the pentobarbital (30 mg/kg) anesthetized cat. Renal blood flow (RBF) was measured with an electromagnetic flow meter. Minimal postocclusive RBF is expressed as percentage decrease of preocclusion RBF. Marked postocclusive vasoconstriction could only be demonstrated in meclofenamate (10 mg/kg) treated cats. Δ% RBF (30 sec occlusion) was in controls 16 ± 4 and after meclofenamate 54 ± 4 (n=10; p < .001). Chronic denervation of the kidney, adrenergic receptor blockade (phenoxybenzamine or phentol-amine), or infusion of 1-Sar-8-Ile-angiotensin II (2 μg/min·kg) did not affect the postocclusive reduction of RBF, indicating that the vasoconstriction was independent of renal nerves, catecholamines and circulating angiotensin II. Adenosine when injected into the renal artery of 5 cats caused a dose dependent transient fall of RBF. 100 nmol adenosine reduced RBF by 44 ± 6% whereas after meclofenamate only 1 nmol produced the same degree of vasoconstriction. Since adenosine accumulates in the kidney several fold following renal artery occlusion (Osswald et al., Pflugers Arch. 371:45, 1977) and the renal vasculature was 100-fold more sensitive to adenosine induced vasoconstriction after meclofenamate treatment we suggest that the response of the renal vasculature following renal artery occlusion is mediated by intrarenal adenosine. Prostaglandins, particularly in the anesthetized animal, can mask the postocclusive vasoconstriction in the kidney.
Methods in Enzymology, 1989
Publisher Summary This chapter describes the immunoadsorption procedures for isolating large, hom... more Publisher Summary This chapter describes the immunoadsorption procedures for isolating large, homogeneous populations of both canine and rabbit collecting tubule cells. Cultures of these cells exhibit a number of the differentiated properties of the parent cells even after several passages. In principle, immunoadsorption should be applicable to isolating any cell type against which a specific antibody is available. The procedures for isolating canine and rabbit cortical collecting tubule cells—canine cortical collecting tubule cells and rabbit cortical collecting tubule cells—are described. Unless one already has available antibodies specific for a cell surface protein on the cell of interest, it is necessary to prepare monoclonal antibodies. For immunodissection, the nature of the antigen is of secondary importance, but it must be an ectoantigen present in relative abundance and only on the cell of interest. It is also important that the antibody be of the immunoglobulin G class because IgGs are more stable and easier to purify. Indirect immunofluorescence is used to test for antibodies to specific renal cell types.
PubMed, Oct 1, 1980
We used very high doses of a competitive inhibitor of angiotensin II to investigate the role of t... more We used very high doses of a competitive inhibitor of angiotensin II to investigate the role of the intrarenal renin-angiotensin system in the autoregulation of renal blood flow. Studies were carried out in dogs in which the renin and prostaglandin systems were suppressed. The results of our studies indicate that angiotensin II is not a prime mediator of the autoregulation of renal blood flow in response to reduced perfusion pressure.
PubMed, Nov 1, 1977
Hydrostatic pressure in the glomerular capillaries, the primary driving force for glomerular ultr... more Hydrostatic pressure in the glomerular capillaries, the primary driving force for glomerular ultrafiltration, is directly measurable only in those species with glomeruli present on the capsular surface of the kidney. Accordingly, this crucial measurement must be made indirectly in species not so endowed, such as the dog. Several different methods have been utilized in the dog; unfortunately each is indirect. This review deals with an assessment of the following methods for the determination of glomerular capillary pressure in dogs: a) reduction of arterial pressure method; b) ureteral occlusion method; c) the Winton or venous occlusion method; d) fraction of arterial pressure method; e) back calculation from forces opposing filtration; f) sieving method; and g) single nephron occlusion of the Gertz stop-flow method. Recent studies in the dog, utilizing single nephron occlusion techniques, provide estimates of glomerular capillary pressures of approximately 60 mn Hg in the autoregulatory range of blood pressure.
PubMed, 1994
[125I]Tyr13-Suc-[Glu9,Ala11,15]-Endothelin-1 (8-21) ([125I]IRL-1620) displayed specific, saturabl... more [125I]Tyr13-Suc-[Glu9,Ala11,15]-Endothelin-1 (8-21) ([125I]IRL-1620) displayed specific, saturable and high affinity binding to membranes prepared from rat and dog cerebellum, rat and human lung and cloned human endothelin-B (ETB) receptors. The apparent dissociation constant (Kd) for rat cerebellum, dog cerebellum, rat lung, human lung and human ETB clone were 69.1, 34.8, 128, 71.9, and 115 pM, respectively. The maximum binding (Bmax) to these membranes were 3.2, 0.71, 1.67, 1.85 and 62.3 pmol/mg of protein for rat cerebellum, dog cerebellum, rat lung, human lung and human ETB clone, respectively. Unlabeled endothelin-1 (ET-1), ET-3 and sarafotoxin 6c (S6c) displaced [125I]IRL-1620 binding to these membranes with similar affinity (IC50 = 0.1-2.5 nM), whereas cyclo(D-Trp,D-Asp,L-Pro,D-Val,L-Leu), a selective antagonist for ETA receptors, had no effect on [125I]IRL-1620 binding up to 1 microM. Time course experiments of association and dissociation indicated that [125]IRL-1620 binding to dog and human tissues and human ETB clone was rapid and reversible, whereas in rat tissues, the binding was rapid but irreversible, suggesting that this might be due to species difference. [125I]ET-1 binding was irreversible in all the tissues tested. No binding of [125I]IRL-1620 was detectable in rat vascular smooth muscle cells or cloned human ETA receptors. These data indicate that [125I]IRL-1620 is highly selective for ETB receptors and the reversible binding characteristics of this ligand appears to be species-dependent.
Microvascular Research, Nov 1, 1984
The duration of the effect of histamine to increase the capillary filtration coefficient (CFC) wa... more The duration of the effect of histamine to increase the capillary filtration coefficient (CFC) was evaluated in isolated, denervated canine forelimb, hindpaw, and gracilis muscle. CFC was estimated at timed intervals during local intraarterial histamine (12 pg base.min-' per 100 ml.min-' blood flow). Propranolol (3 mg/kg) was administered to inhibit possible catecholamine-mediated inhibition of histamine-induced increases in CFC. The increase in CFC was greatest after 10 min of drug infusion and returned to control values after 25 min of histamine. These data indicate that the effect of histamine to increase CFC is highly transient. The relative contributions of increases in surface area and/or permeability to increases in CFC were assessed by maximally dilating the vasculatures of the three tissues with nitroprusside (increasing surface area to a maximum). Any further increase in CFC produced by combined nitroprusside-histamine infusion would then be due to increased permeability. Histamine, when infused concomitantly with nitroprusside, produced further increases in CFC relative to CFC obtained during infusion of nitroprusside alone. The time course for the transient increase in CFC during combined histamine-nitroprusside infusion was similar to the time course during histamine alone. These data suggest that the transient increase in CFC induced by histamine is primarily mediated by a transient increase in microvascular permeability to fluid in all three tissues. The transient nature of this increase in permeability was probably not related to a P-antagonistic action of the catecholamines (which may have been increased reflexly) because these tissues were pblocked with propranolol. An equation was derived to estimate the ratio of the number of gaps which form between venular endothelial cells to the number of small pores. It was concluded that less than 3% of small pores need increase in radius to form large pores or gaps with radii ranging from 195 to 1000 A to explain the increases in CFC demonstrated in the hindpaw and gracilis muscle and that structures beyond the microvascular endothelium may provide the principle resistance to fluid efhux during histamine. Q 1984 Academic press, Inc.
American Journal of Physiology-renal Physiology, Oct 1, 1978
In contrast to the postocclusive hyperemia of brain, heart, and skeletal muscle, the hemodynamic ... more In contrast to the postocclusive hyperemia of brain, heart, and skeletal muscle, the hemodynamic response of the kidney following renal artery occlusion is highly variable in that both hyperemia and ischemia have been reported. The present study evaluates the factors influencing the renal response to complete renal artery occlusion (5-60 s) in the anesthetized cat. Marked postocclusive vasoconstriction could only be domonstrated in meclofenamate-treated (10 mg/kg) cats. The delta% renal blood flow (RBF) (30-s occlusion) was 16 +/- 4 in controls and 54 +/- 4 after meclofenamate (n= 10; P less than 0.001). Chronic denervation of the kidney, alpha-adrenergic receptor blockade, or infusion of [Sar1, Ile8]angiotensin II(2 microgram/min per kg) did not affect the postocclusive reduction of RBF, indicating that the vasoconstriction was independent of renal nerves, catecholamines, and circulating angiotesin II. Adenosine injected into the renal artery of five cats caused a dose-dependent transient fall of RBF. A dose of 100 nmol adenosine reduced RBF by 44 +/- 6% whereas after meclofenamate only 1 nmol produced the same degree of vasoconstriction. In summary, this study demonstrates a marked potentiation of the postocclusive vasoconstrictor response and the vasoconstrictive action of adenosine by meclofenamate in the anesthetized animal. No evidence was obtained to support a role for the sympathetic nervous system or circulating angiotensin II in mediating the postocclusive vasoconstriction.
American Journal of Physiology-renal Physiology, Aug 1, 1984
The action of theophylline on the adenosine-induced decrease in renin release was studied in anes... more The action of theophylline on the adenosine-induced decrease in renin release was studied in anesthetized dogs. Adenosine inhibited renin release, decreased GFR and fractional sodium excretion, and decreased the concentration of angiotensin II in the renal lymph. Theophylline (5 mumol/min intrarenally) had no significant effect on GFR or RBF yet produced a significant increase in the release of renin and the fractional excretion of sodium. The intrarenal infusion of adenosine (3 X 10(-7) mol/min) during theophylline infusion produced no effect on GFR or RBF, but fractional sodium excretion and renin release were significantly decreased. Adenosine was infused at a lower dose (3 X 10(-8) mol/min) during theophylline (5 X 10(-6) mol/min) infusion in a second group of dogs. With the exception of fractional sodium excretion, all effects of adenosine were effectively antagonized by theophylline. Theophylline at 5 X 10(-6) mol/min, which stimulates renin release and effectively antagonizes the renal effects of adenosine, had no detectable effect on cAMP measured in renal cortex. Furthermore, no change in cortical cAMP was observed until theophylline was increased 50-fold over the dose effective in antagonizing adenosine. These findings demonstrate that theophylline, at concentrations having no effect on cortical cAMP, antagonizes the effect of adenosine on renin release. The results are also consistent with the view that theophylline stimulates renin release by a mechanism other than its action on cAMP.
The effects of arginine vasopressin (AVP) on the cytosolic free calcium concentration (ICa"2jf) w... more The effects of arginine vasopressin (AVP) on the cytosolic free calcium concentration (ICa"2jf) were examined in freshly immunodissected rabbit cortical collecting tubule cells using fluorescent Ca"2 indicators fura-2 and indo-1. The addition of AVP to a cell suspension resulted in a rapid and transient increase in the [Ca"2If. The 1-deamino-8-D-AVP (dDVP), a V2 receptor agonist of AVP that stimulated adenosine 3',5' cAMP production in these cells, had no effect on ICa+2if and did not affect AVP-induced increase in [Ca+2Jf. The AVP-induced increase in [Ca+2If but not cAMP production was blocked by the V1 receptor antagonist, [1-(beta-mercapto-beta-beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosinel Arg8-vasopressin. The AVP-stimulated increase in [Ca+2jf appeared to be largely due to Ca+2 release from intracellular stores as reduction of extracellular Ca+2 with EGTA had little if any effect on the AVP-induced increase in [Ca+21f. This AVP-induced increase in [Ca+2If was associated with an increase in inositol-1,4,5-trisphosphate production and appeared to involve a guanine nucleotide-binding protein (G), since the pretreatment of cells with pertussis toxin for 4-6 h inhibited this effect. Finally, measurements of [Ca+2If in single cells suggest that only the principal cells of the collecting tubules respond to AVP with an increase in ICa+2If. In summary, these results demonstrate that the principal cells of the cortical collecting tubule possess two distinct receptor systems for vasopressin, the well-known V2 receptor coupled to adenylate cyclase, and a VI receptor system that leads to the mobilization of cytosolic calcium, coupled through a pertussis toxin substrate (G protein) to a production of inositol phosphates.
American Journal of Physiology-Renal Physiology, 1980
Acute left renal denervation in anesthetized volume-expanded rats produced an ipsilateral diuresi... more Acute left renal denervation in anesthetized volume-expanded rats produced an ipsilateral diuresis and natriuresis in 19 animals. A simultaneous decrease of glomerular filtration rate, p-aminohippurate clearance, urinary volume (P < 0.002), and percentage of filtered sodium excreted (4.0 +/- 0.6 (SE) vs. 1.9 +/- 0.4%, P < 0.003) occurred in the right innervated kidney in 10 rats. Prior denervation of the right kidney in the other nine rats prevented the renal hemodynamic changes and the fall of urinary volume and of sodium excretion (3.9 +/- 0.6 vs. 4.3 +/- 0.5%) by the right kidney after left renal denervation. Nerve traffic to the right kidney was measured in six other animals after left renal denervation and was found to increase to a mean value 33.8 +/- 6.3% above control levels (P < 0.007) 0-30 min after denervation, with a further significant increase to 66.2 +/- 16.1% above control levels (P < 0.025) 30-60 min after denervation. These results indicate that the fun...
American Journal of Physiology, Jul 1, 1976
The APS Journal Legacy Content is the corpus of 100 years of historical scientific research from ... more The APS Journal Legacy Content is the corpus of 100 years of historical scientific research from the American Physiological Society research journals. This package goes back to the first issue of each of the APS journals including the American Journal of Physiology, first published in 1898. The full text scanned images of the printed pages are easily searchable. Downloads quickly in PDF format.
American Journal of Physiology, Aug 1, 1975
Dogs with experimental high-output heart failure (HOF) exhibit marked retention of salt and water... more Dogs with experimental high-output heart failure (HOF) exhibit marked retention of salt and water secondary to hypersecretion of both renin and aldosterone. The present study was undertaken to evaluate the systemic and intrarenal arteriolar action of angiotensin II (AII) in dogs with HOF and to provide additional information about the role of AII in low-output states. The intravenous infusion of a specific AII antagonist, [Sar1, Ala8]AII (6 mug/kg min-1), into conscious dogs with HOF decreased the mean arterial pressure (AP) from 101 +/- 7 to 83 +/- 7 mmHg (P less than 0.01) after 45 min of infusion. Intrarenal arterial infusion of the AII antagonist (0.2 and 2.0 mug/kg min-1) into anesthetized dogs with HOF also decreased AP and produced a marked increase in renal blood flow (RBF) with no changes in either creatinine clearance or sodium excretion. Similar results were obtained during the intrarenal infusion of the antagonist into sodium-depleted dogs and dogs with thoracic vena caval constriction, but not in normal dogs. The data demonstrate an important role for AII in the regulation of AP and RBF in high- and low-output states.
PubMed, 1975
The rate of metabolism of aldosterone was measured in seven normal dogs, 4 dogs with chronic rena... more The rate of metabolism of aldosterone was measured in seven normal dogs, 4 dogs with chronic renal hypertension and five dogs with malignant renal hypertension. Tritiated aldosterone was injected intravenously and the rate of disappearance of authentic aldosterone was determined. The disappearance curves were resolved into two exponential components and the plasma half-life was measured from the slow component which reflects the rate of metabolism of aldosterone. The half-life of aldosterone was essentially the same for the three groups of dogs. It is concluded, therefore, that the rate of aldosterone metabolism is normal in dogs with experimental renal hypertension.
American Journal of Physiology-Cell Physiology, 1991
We studied the effect of cadmium, verapamil, and quinacrine on the force of contraction (Fp) of i... more We studied the effect of cadmium, verapamil, and quinacrine on the force of contraction (Fp) of isolated, single, field-stimulated bullfrog atrial cells. All agents were applied or removed rapidly (t1/2 approximately 15 ms) to minimize intracellular concentration changes other than intracellular calcium concentration. Two components of twitch force were observed, one blocked by micromolar Cd2+ and the other by millimolar Cd2+. The two contributed about equally to the activation of the twitch. The "cadmium-sensitive" portion of force (that affected by [Cd] less than or equal to 100 microM) had a K1/2 approximately 1 microM, was identical in magnitude to, and not additive with, a "verapamil-sensitive" (10 microM) component of force, was most strongly affected by 50-ms pulses of Cd2+ when they were applied in the mechanical latent period, and was potentiated by catecholamines. The cadmium-insensitive portion of force was abolished by the removal of extracellular cal...
Japanese Journal of Pharmacology, 1990
Annals of Biomedical Engineering, Jun 29, 1983
In contrast to the postocclusive hyperemia of brain, heart, and skeletal muscle, the hemodynamic ... more In contrast to the postocclusive hyperemia of brain, heart, and skeletal muscle, the hemodynamic response of the kidney following renal artery occlusion is highly variable in that both hyperemia and ischemia have been reported. The present study evaluates the factors influencing the renal response to complete renal artery occlusion (5–60 sec) in the pentobarbital (30 mg/kg) anesthetized cat. Renal blood flow (RBF) was measured with an electromagnetic flow meter. Minimal postocclusive RBF is expressed as percentage decrease of preocclusion RBF. Marked postocclusive vasoconstriction could only be demonstrated in meclofenamate (10 mg/kg) treated cats. Δ% RBF (30 sec occlusion) was in controls 16 ± 4 and after meclofenamate 54 ± 4 (n=10; p < .001). Chronic denervation of the kidney, adrenergic receptor blockade (phenoxybenzamine or phentol-amine), or infusion of 1-Sar-8-Ile-angiotensin II (2 μg/min·kg) did not affect the postocclusive reduction of RBF, indicating that the vasoconstriction was independent of renal nerves, catecholamines and circulating angiotensin II. Adenosine when injected into the renal artery of 5 cats caused a dose dependent transient fall of RBF. 100 nmol adenosine reduced RBF by 44 ± 6% whereas after meclofenamate only 1 nmol produced the same degree of vasoconstriction. Since adenosine accumulates in the kidney several fold following renal artery occlusion (Osswald et al., Pflugers Arch. 371:45, 1977) and the renal vasculature was 100-fold more sensitive to adenosine induced vasoconstriction after meclofenamate treatment we suggest that the response of the renal vasculature following renal artery occlusion is mediated by intrarenal adenosine. Prostaglandins, particularly in the anesthetized animal, can mask the postocclusive vasoconstriction in the kidney.
Methods in Enzymology, 1989
Publisher Summary This chapter describes the immunoadsorption procedures for isolating large, hom... more Publisher Summary This chapter describes the immunoadsorption procedures for isolating large, homogeneous populations of both canine and rabbit collecting tubule cells. Cultures of these cells exhibit a number of the differentiated properties of the parent cells even after several passages. In principle, immunoadsorption should be applicable to isolating any cell type against which a specific antibody is available. The procedures for isolating canine and rabbit cortical collecting tubule cells—canine cortical collecting tubule cells and rabbit cortical collecting tubule cells—are described. Unless one already has available antibodies specific for a cell surface protein on the cell of interest, it is necessary to prepare monoclonal antibodies. For immunodissection, the nature of the antigen is of secondary importance, but it must be an ectoantigen present in relative abundance and only on the cell of interest. It is also important that the antibody be of the immunoglobulin G class because IgGs are more stable and easier to purify. Indirect immunofluorescence is used to test for antibodies to specific renal cell types.
PubMed, Oct 1, 1980
We used very high doses of a competitive inhibitor of angiotensin II to investigate the role of t... more We used very high doses of a competitive inhibitor of angiotensin II to investigate the role of the intrarenal renin-angiotensin system in the autoregulation of renal blood flow. Studies were carried out in dogs in which the renin and prostaglandin systems were suppressed. The results of our studies indicate that angiotensin II is not a prime mediator of the autoregulation of renal blood flow in response to reduced perfusion pressure.
PubMed, Nov 1, 1977
Hydrostatic pressure in the glomerular capillaries, the primary driving force for glomerular ultr... more Hydrostatic pressure in the glomerular capillaries, the primary driving force for glomerular ultrafiltration, is directly measurable only in those species with glomeruli present on the capsular surface of the kidney. Accordingly, this crucial measurement must be made indirectly in species not so endowed, such as the dog. Several different methods have been utilized in the dog; unfortunately each is indirect. This review deals with an assessment of the following methods for the determination of glomerular capillary pressure in dogs: a) reduction of arterial pressure method; b) ureteral occlusion method; c) the Winton or venous occlusion method; d) fraction of arterial pressure method; e) back calculation from forces opposing filtration; f) sieving method; and g) single nephron occlusion of the Gertz stop-flow method. Recent studies in the dog, utilizing single nephron occlusion techniques, provide estimates of glomerular capillary pressures of approximately 60 mn Hg in the autoregulatory range of blood pressure.
PubMed, 1994
[125I]Tyr13-Suc-[Glu9,Ala11,15]-Endothelin-1 (8-21) ([125I]IRL-1620) displayed specific, saturabl... more [125I]Tyr13-Suc-[Glu9,Ala11,15]-Endothelin-1 (8-21) ([125I]IRL-1620) displayed specific, saturable and high affinity binding to membranes prepared from rat and dog cerebellum, rat and human lung and cloned human endothelin-B (ETB) receptors. The apparent dissociation constant (Kd) for rat cerebellum, dog cerebellum, rat lung, human lung and human ETB clone were 69.1, 34.8, 128, 71.9, and 115 pM, respectively. The maximum binding (Bmax) to these membranes were 3.2, 0.71, 1.67, 1.85 and 62.3 pmol/mg of protein for rat cerebellum, dog cerebellum, rat lung, human lung and human ETB clone, respectively. Unlabeled endothelin-1 (ET-1), ET-3 and sarafotoxin 6c (S6c) displaced [125I]IRL-1620 binding to these membranes with similar affinity (IC50 = 0.1-2.5 nM), whereas cyclo(D-Trp,D-Asp,L-Pro,D-Val,L-Leu), a selective antagonist for ETA receptors, had no effect on [125I]IRL-1620 binding up to 1 microM. Time course experiments of association and dissociation indicated that [125]IRL-1620 binding to dog and human tissues and human ETB clone was rapid and reversible, whereas in rat tissues, the binding was rapid but irreversible, suggesting that this might be due to species difference. [125I]ET-1 binding was irreversible in all the tissues tested. No binding of [125I]IRL-1620 was detectable in rat vascular smooth muscle cells or cloned human ETA receptors. These data indicate that [125I]IRL-1620 is highly selective for ETB receptors and the reversible binding characteristics of this ligand appears to be species-dependent.
Microvascular Research, Nov 1, 1984
The duration of the effect of histamine to increase the capillary filtration coefficient (CFC) wa... more The duration of the effect of histamine to increase the capillary filtration coefficient (CFC) was evaluated in isolated, denervated canine forelimb, hindpaw, and gracilis muscle. CFC was estimated at timed intervals during local intraarterial histamine (12 pg base.min-' per 100 ml.min-' blood flow). Propranolol (3 mg/kg) was administered to inhibit possible catecholamine-mediated inhibition of histamine-induced increases in CFC. The increase in CFC was greatest after 10 min of drug infusion and returned to control values after 25 min of histamine. These data indicate that the effect of histamine to increase CFC is highly transient. The relative contributions of increases in surface area and/or permeability to increases in CFC were assessed by maximally dilating the vasculatures of the three tissues with nitroprusside (increasing surface area to a maximum). Any further increase in CFC produced by combined nitroprusside-histamine infusion would then be due to increased permeability. Histamine, when infused concomitantly with nitroprusside, produced further increases in CFC relative to CFC obtained during infusion of nitroprusside alone. The time course for the transient increase in CFC during combined histamine-nitroprusside infusion was similar to the time course during histamine alone. These data suggest that the transient increase in CFC induced by histamine is primarily mediated by a transient increase in microvascular permeability to fluid in all three tissues. The transient nature of this increase in permeability was probably not related to a P-antagonistic action of the catecholamines (which may have been increased reflexly) because these tissues were pblocked with propranolol. An equation was derived to estimate the ratio of the number of gaps which form between venular endothelial cells to the number of small pores. It was concluded that less than 3% of small pores need increase in radius to form large pores or gaps with radii ranging from 195 to 1000 A to explain the increases in CFC demonstrated in the hindpaw and gracilis muscle and that structures beyond the microvascular endothelium may provide the principle resistance to fluid efhux during histamine. Q 1984 Academic press, Inc.
American Journal of Physiology-renal Physiology, Oct 1, 1978
In contrast to the postocclusive hyperemia of brain, heart, and skeletal muscle, the hemodynamic ... more In contrast to the postocclusive hyperemia of brain, heart, and skeletal muscle, the hemodynamic response of the kidney following renal artery occlusion is highly variable in that both hyperemia and ischemia have been reported. The present study evaluates the factors influencing the renal response to complete renal artery occlusion (5-60 s) in the anesthetized cat. Marked postocclusive vasoconstriction could only be domonstrated in meclofenamate-treated (10 mg/kg) cats. The delta% renal blood flow (RBF) (30-s occlusion) was 16 +/- 4 in controls and 54 +/- 4 after meclofenamate (n= 10; P less than 0.001). Chronic denervation of the kidney, alpha-adrenergic receptor blockade, or infusion of [Sar1, Ile8]angiotensin II(2 microgram/min per kg) did not affect the postocclusive reduction of RBF, indicating that the vasoconstriction was independent of renal nerves, catecholamines, and circulating angiotesin II. Adenosine injected into the renal artery of five cats caused a dose-dependent transient fall of RBF. A dose of 100 nmol adenosine reduced RBF by 44 +/- 6% whereas after meclofenamate only 1 nmol produced the same degree of vasoconstriction. In summary, this study demonstrates a marked potentiation of the postocclusive vasoconstrictor response and the vasoconstrictive action of adenosine by meclofenamate in the anesthetized animal. No evidence was obtained to support a role for the sympathetic nervous system or circulating angiotensin II in mediating the postocclusive vasoconstriction.
American Journal of Physiology-renal Physiology, Aug 1, 1984
The action of theophylline on the adenosine-induced decrease in renin release was studied in anes... more The action of theophylline on the adenosine-induced decrease in renin release was studied in anesthetized dogs. Adenosine inhibited renin release, decreased GFR and fractional sodium excretion, and decreased the concentration of angiotensin II in the renal lymph. Theophylline (5 mumol/min intrarenally) had no significant effect on GFR or RBF yet produced a significant increase in the release of renin and the fractional excretion of sodium. The intrarenal infusion of adenosine (3 X 10(-7) mol/min) during theophylline infusion produced no effect on GFR or RBF, but fractional sodium excretion and renin release were significantly decreased. Adenosine was infused at a lower dose (3 X 10(-8) mol/min) during theophylline (5 X 10(-6) mol/min) infusion in a second group of dogs. With the exception of fractional sodium excretion, all effects of adenosine were effectively antagonized by theophylline. Theophylline at 5 X 10(-6) mol/min, which stimulates renin release and effectively antagonizes the renal effects of adenosine, had no detectable effect on cAMP measured in renal cortex. Furthermore, no change in cortical cAMP was observed until theophylline was increased 50-fold over the dose effective in antagonizing adenosine. These findings demonstrate that theophylline, at concentrations having no effect on cortical cAMP, antagonizes the effect of adenosine on renin release. The results are also consistent with the view that theophylline stimulates renin release by a mechanism other than its action on cAMP.
The effects of arginine vasopressin (AVP) on the cytosolic free calcium concentration (ICa"2jf) w... more The effects of arginine vasopressin (AVP) on the cytosolic free calcium concentration (ICa"2jf) were examined in freshly immunodissected rabbit cortical collecting tubule cells using fluorescent Ca"2 indicators fura-2 and indo-1. The addition of AVP to a cell suspension resulted in a rapid and transient increase in the [Ca"2If. The 1-deamino-8-D-AVP (dDVP), a V2 receptor agonist of AVP that stimulated adenosine 3',5' cAMP production in these cells, had no effect on ICa+2if and did not affect AVP-induced increase in [Ca+2Jf. The AVP-induced increase in [Ca+2If but not cAMP production was blocked by the V1 receptor antagonist, [1-(beta-mercapto-beta-beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosinel Arg8-vasopressin. The AVP-stimulated increase in [Ca+2jf appeared to be largely due to Ca+2 release from intracellular stores as reduction of extracellular Ca+2 with EGTA had little if any effect on the AVP-induced increase in [Ca+21f. This AVP-induced increase in [Ca+2If was associated with an increase in inositol-1,4,5-trisphosphate production and appeared to involve a guanine nucleotide-binding protein (G), since the pretreatment of cells with pertussis toxin for 4-6 h inhibited this effect. Finally, measurements of [Ca+2If in single cells suggest that only the principal cells of the collecting tubules respond to AVP with an increase in ICa+2If. In summary, these results demonstrate that the principal cells of the cortical collecting tubule possess two distinct receptor systems for vasopressin, the well-known V2 receptor coupled to adenylate cyclase, and a VI receptor system that leads to the mobilization of cytosolic calcium, coupled through a pertussis toxin substrate (G protein) to a production of inositol phosphates.
American Journal of Physiology-Renal Physiology, 1980
Acute left renal denervation in anesthetized volume-expanded rats produced an ipsilateral diuresi... more Acute left renal denervation in anesthetized volume-expanded rats produced an ipsilateral diuresis and natriuresis in 19 animals. A simultaneous decrease of glomerular filtration rate, p-aminohippurate clearance, urinary volume (P < 0.002), and percentage of filtered sodium excreted (4.0 +/- 0.6 (SE) vs. 1.9 +/- 0.4%, P < 0.003) occurred in the right innervated kidney in 10 rats. Prior denervation of the right kidney in the other nine rats prevented the renal hemodynamic changes and the fall of urinary volume and of sodium excretion (3.9 +/- 0.6 vs. 4.3 +/- 0.5%) by the right kidney after left renal denervation. Nerve traffic to the right kidney was measured in six other animals after left renal denervation and was found to increase to a mean value 33.8 +/- 6.3% above control levels (P < 0.007) 0-30 min after denervation, with a further significant increase to 66.2 +/- 16.1% above control levels (P < 0.025) 30-60 min after denervation. These results indicate that the fun...
American Journal of Physiology, Jul 1, 1976
The APS Journal Legacy Content is the corpus of 100 years of historical scientific research from ... more The APS Journal Legacy Content is the corpus of 100 years of historical scientific research from the American Physiological Society research journals. This package goes back to the first issue of each of the APS journals including the American Journal of Physiology, first published in 1898. The full text scanned images of the printed pages are easily searchable. Downloads quickly in PDF format.
American Journal of Physiology, Aug 1, 1975
Dogs with experimental high-output heart failure (HOF) exhibit marked retention of salt and water... more Dogs with experimental high-output heart failure (HOF) exhibit marked retention of salt and water secondary to hypersecretion of both renin and aldosterone. The present study was undertaken to evaluate the systemic and intrarenal arteriolar action of angiotensin II (AII) in dogs with HOF and to provide additional information about the role of AII in low-output states. The intravenous infusion of a specific AII antagonist, [Sar1, Ala8]AII (6 mug/kg min-1), into conscious dogs with HOF decreased the mean arterial pressure (AP) from 101 +/- 7 to 83 +/- 7 mmHg (P less than 0.01) after 45 min of infusion. Intrarenal arterial infusion of the AII antagonist (0.2 and 2.0 mug/kg min-1) into anesthetized dogs with HOF also decreased AP and produced a marked increase in renal blood flow (RBF) with no changes in either creatinine clearance or sodium excretion. Similar results were obtained during the intrarenal infusion of the antagonist into sodium-depleted dogs and dogs with thoracic vena caval constriction, but not in normal dogs. The data demonstrate an important role for AII in the regulation of AP and RBF in high- and low-output states.
PubMed, 1975
The rate of metabolism of aldosterone was measured in seven normal dogs, 4 dogs with chronic rena... more The rate of metabolism of aldosterone was measured in seven normal dogs, 4 dogs with chronic renal hypertension and five dogs with malignant renal hypertension. Tritiated aldosterone was injected intravenously and the rate of disappearance of authentic aldosterone was determined. The disappearance curves were resolved into two exponential components and the plasma half-life was measured from the slow component which reflects the rate of metabolism of aldosterone. The half-life of aldosterone was essentially the same for the three groups of dogs. It is concluded, therefore, that the rate of aldosterone metabolism is normal in dogs with experimental renal hypertension.