Effects of captopril on ischemia-reperfusion induced arrhythmias in rats (original) (raw)
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Ion Transport in Red Blood Cells and Antihypertensive Therapy
Annals of the New York Academy of Sciences, 1986
Many abnormalities in cell membrane transport of ions have been reported to occur in blood cells from patients with essential hyperten~ion.'-~ It is not clear whether these abnormalities are genetically linked to hypertension development or if they are secondary changes mediated by humoral factors or if they are an epiphenomenon without any relationship with hypertension. In order to investigate the effects of the antihypertensive therapy on cation fluxes, 23 hypertensive patients have been treated with Atenolol (AT) 100 mg, Captopril (CP) 75 mg, and Canrenoate K (CK) 200 mg. Each patient received the three drugs TABLE I. Effects of Captopril, Atenolol, and Canrenoate K on Blood Pressure and Heart Rate Basal Captopril Atenolol Canrenoate K S.B.P.ortho
1992
xiv (Chapter 1) Introduction and Aims 1 1.1 Some aspects of cell volume and pH regulation 2 1.11 Cell volume regulation 2 1.12 Cell pH regulation 7 1.121 Na+IH+ antiporter 9 1.122 Sodium-dependent and -independent bicarbonate!chloride exchange 10 1.123 Lactate/Monocarboxylate exchanger 11 1.124 Intrinsic buffering 11 1.2 Some ion transport abnormalities in genetic hypertension 12 1.3 Some problems with in vitro measurement of ion transport 12 1.31 Cell preparation 15 1.32 Method ofmeasurement 16 1.33 Interpretation of results 18 1.4 The aims of this project 18 1.5 Summary 20 (Chapter 2) General Methods 21 2.1 Radiochemicals 22 2.2 Drugs and Reagents 22 2.3 Method for measuring absolute concentrations of rubidium in vivo 07 using Rb NMR spectroscopy 22
Hypertension, 1987
Environmental factors, genetic polymorphisms, and different experimental designs have been the main impediments to evaluating a genetic association between cell membrane cation transport abnormalities and human essential or genetic hypertension. We review the results obtained in the Milan hypertensive strain of rats (MHS) and in its appropriate control normotensive strain (MNS) to illustrate our approach to defining the role of cation transport abnormality in a type of genetic hypertension. Before the development of a difference in blood pressure between the two strains, the comparison of kidney and erythrocyte functions showed that MHS had an increased glomerular filtration rate and urinary output, and lower plasma renin and urine osmolality. Kidney cross-transplantation between the strains showed that hypertension is transplanted with the kidney. Proximal tubular cell volume and sodium content were lower in MHS while sodium transport across the brush border membrane vesicles of MHS was faster. Erythrocytes in MHS were smaller and had lower sodium concentration, and Na +-K + cotransport and passive permeability were faster. The differences in volume, sodium content, and Na +-K + cotransport between erythrocytes of the two strains persisted after transplantation of bone marrow to irradiated F, (MHS x MNS) hybrids. Moreover, in normal segregating F 2 hybrid populations there was a positive correlation between blood pressure and Na +-K + cotransport. These results suggest a genetic and functional link in MHS between cell membrane cation transport abnormalities and hypertension. Thus erythrocyte cell membrane may be used for approaching the problem of defining the genetically determined molecular mechanism underlying the development of a type of essential hypertension.
Erythrocyte Membrane Transport Systems as Possible Markers for Essential Hypertension
Clinical science. Supplement (1979), 1982
Na+-Li+ countertransport were measured at the same time in 56 essential hypertensive patients, 24 of their normotensive offspring and 36 matched normotensive controls. 2. The mean value of Na+-K+ cotransport is slower and of Na+-Li+ countertransport is faster in the essential hypertensive group and in some of their normotensive offspring, but a great overlap with the value of the normotensive group was observed. 3. Na+-K+ cotransport values were bimodally distributed in the hypertensive group, with the first mode at 250 and the second at 600 pmol h-' 1-' of erythrocytes. 4. The ratio Na+-K+ cotransport/Na+-Li+ countertransport was calculated. It was found that such a ratio distinguishes between normotensive and essential hypertensive subjects better than the individual transport systems alone.
Erythrocyte Na-K-Cl Cotransport Activity in Low Renin Essential Hypertensive Patients
American Journal of Hypertension, 1994
The Na-K-Cl cotransport activity in red blood cells from essential hypertensive men with low (n = 8, mean age 42 ± 4 years) or normal renin activity (n = 4, mean age 43 ± 3 years), and in normotensive men with normal renin activity (n = 7, mean age 38 ± 4 years) has been evaluated by means of a recently developed M Na nuclear magnetic reso nance (NMR) method. Sodium efflux was deter mined by relating the resonating frequency of the NMR signal from extracellular sodium to sodium concentration in the presence of the shift reagent Dy(PPP) 2 7 ". The maximum Na + efflux driven by cotransport (V max) was measured in Na +-loaded erythrocytes in the presence of ouabain to block the Na-K-Cl pump activity. A significant differ ence (P < 0.05) was found in V max values of low renin patients (0.70 mmol/h/L cells, range 0.40 to 0.90 mmol/h/L cells) as compared with normoten sive controls (0.39 ± 0.08 mmol/h/L cells) and nor mal renin hypertensives (mean 0.49 ± 0.04 mmol/ h/L cells). In conclusion, this study showed an in creased activity of the Na-K-Cl cotransport in red blood cells from low renin hypertensive men as compared with normal renin hypertensives and normotensives. Am J Hypertens 1994;7:151-158 KEY WORDS: Sodium, potassium, cell membrane permeability, renin-angiotensin system, hyperten sion. ome reports in the literature indicate that es sential hypertension is characterized by a het erogeneous behavior as far as the Na-K-Cl cotransport activity is concerned. 1 In animal models, Ferrari et al 2 have demonstrated that Milan hypertensive (MHS) rats, compared with the normotensive control strain Milan normotensive (MNS) rats, have a faster erythrocyte Na-K-Cl cotransport activity. However, the Na-K-Cl cotrans port activity is normal in Sabra hypertensive rats, 3
Calcium transport in basolateral plasma membranes from kidney cortex of Milan hypertensive rats
Biochimica Et Biophysica Acta Biomembranes, 1988
Ca 2 + transport was investigated in hasolateral plasma membranes (BLM) isolated from kidney cortex of the Milan strain of genetically hypertensive rats (MHS) and their normotensive controls (MNS) during a pre-hypertensive stage (age 3-4 weeks). It was found that the Vm~ of ATP-dependent Ca 2 ÷ transport (in the presence of calmodulin) was about 16% lower in MIlS than in control rats. In membranes from MNS rats which had been isolated in the presence of EGTA, the ATP-dependent Ca 2 + transport showed a hyperbolic Ca 2÷ concentration dependence, a high K m (Ca 2+) and a low V.~,; upon addition of exogenous calmodulin, the kinetics became sigmoidal, the K m (Ca 2+) was decreased and the Vmx was increased. In membranes from MHS rats, the Ca 2÷ concentration dependence of ATP-driven Ca 2÷ transport was signmidai and the Ca 2+ affinity was high in the absence of added calmodulin. Addition of exogenous calmodulin to these membranes resulted in an increase in Vmx, but no change in other kinetic parameters. Low-affinity hyperbolic kinetics of Ca 2+ transport could only be obtained in MHS rats if the membranes were extracted with hypotonic EDTA and hypertonic KCI. These data suggest that the plasma membrane Ca2+-ATPase, which catalyses the ATP-dependent Ca 2÷ transport, exists in BLM of pre-hypertensive MHS rats predominantly in an activated, high-affinity form.
Hypertension, 1984
External K + inhibits the maximal rate of outward Na + , K + cotransport in human red cells with no effect on the apparent affinity for internal Na +. The K + concentration giving halfmaximal inhibition (K K) varied from 16 to 30 mM in 24 normotensive control subjects. Six of the 38 hypertensive patients showed a K IK above the upper limit of this normal range. Only three hypertensive patients showed a K IK below normal range. The internal Na + content giving half-maximal stimulation of outward Na + , K + cotransport (K^ was measured in the hypertensive patients (a normal range of K^ = 9 to 16 mmol/liter cells was previously established in 50 normotensive control subjects). Eighteen hypertensive patients showed an abnormally high K SNl , as previously described in hypertensive patients whose Na + , K + cotransport system had a low affinity for internal Na + (Co 0). Comparison of K SN , with K, K showed that all six hypertensive patients with high K K and all three hypertensive patients with low K u were Co 0 hypertensive. (Hypertension 6: 352-359, 1984) KEY WORDS • Na + transport • Na + permeability • human, erythrocytes • hypertension W E have previously reported that the erythrocyte Na + , K + cotransport system catalyzes low outward Na + fluxes in a high proportion of patients with essential hypertension. 1 ' 2 At the same time, Canessa et al. 3 observed that most patients with essential hypertension were characterized by high Na + , Li + countertransport fluxes. Several other laboratories" have reported extremely variable proportions of hypertensive patients with low outward cotransport or high countertransport fluxes (see reference 4, Table 3, for a summary of these results). Later, Adragna et al. 3 claimed that outward Na + ,K + cotransport was increased in essential hypertension. The results on inward Na + , K + cotransport fluxes are also controversial. Ghione et al. 6 first reported that low outward Na + cotransport was not always well correlated with low inward K + cotransport. Later, Duhm et al. 7 confirmed the absence of a major abnormality of inward K + cotransport fluxes.
Intracellular calcium concentration and activation of the Na+/H+ exchanger in essential hypertension
Kidney International, 1994
Intracellular calcium concentration and activation of the Na/W exchanger in essential hypertension. To investigate the relationship between changes in intracellular calcium concentration ([Ca211,) and agonist-induced activation of the Na/H exchanger in essential hypertension (EH), platelet [Ca2]1 and pH1 were measured in 24 patients with EH (14 males) aged 48 2 years and 23 matched normotensive controls (NT) (12 males) aged 45 3 years. Measurements were done with spectrofluorimetry using the dyes Fura-2 for [Ca2]1 and BCECF for pH1.
Pfl�gers Archiv European Journal of Physiology, 1983
The goal of this study was to determine whether the elevated flux of sodium and potassium through the erythrocyte membrane of spontaneously hypertensive rats (SHR) is due to an intrinsic difference in the cell membrane or to a humoral factor present in the plasma. Isolated and washed erythrocytes from SHR and normotensive Wistar Kyoto (WKy) and Sprague-Dawley (SD) rats, were incubated in 1) a physiological salt solution, 2) WKy or SD plasma and 3) SHR plasma. Incubations were performed at 4~ for 23 h. Erythrocytes from SHR incubated in physiological salt solution had significantly greater Na + and K + fluxes than those from normotensive WKy and SD rats (P < 0.005). Plasma from any of the three strains of rats, as compared to physiological salt solution, increased Na + influx in the following order: SD > WKy > SHR. Erythrocyte K + efflux was not altered by plasma. We conclude that the elevated flux of Na + and K + in SHR erythrocytes is due to an intrinsic difference in the cell membrane. The greater Na § influx in plasma from any strain of rats is not correlated with the blood pressure of the rat. The lesser increase in Na + influx in erythrocytes incubated in plasma from SHR masks the greater intrinsic membrane permeability in the SHR erythrocyte when Na § fluxes are studied in whole blood. The elevated flux of Na + and K + through the erythrocyte membrane of SHR may reflect a general membrane defect that underlies the pathogenesis of elevated arterial pressure.