Responses of the Cardiovascular System of the Rat to Noradrenaline Infusions and Their Modification by Adrenoceptor Blocking Agents (original) (raw)
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Pressor effects of noradrenaline injected into the lateral septal area of unanesthetized rats
Brain Research, 2006
The lateral septal area (LSA) is involved in central cardiovascular control. In the present study, we report on the cardiovascular effects of noradrenaline (NA) injection into the LSA of unanesthetized rats, as well as on local receptors and peripheral mechanisms involved in their mediation. Microinjections of NA (9, 15, 21, 27 or 45 nmol) caused long-lasting, doserelated pressor and bradycardic responses in unanesthetized rats. No responses were observed when the dose of 21 nmol of NA was microinjected into medial septal area or lateral ventricle suggesting a main action at the LSA. No changes were observed in arterial pressure and heart rate when NA was injected in the LSA of anesthetized rats. The effects of 21 nmol of NA were abolished by local pretreatment with 10 nmol of the specific α 1 -receptor antagonist WB 4101, but were not affected by pretreatment with 10 nmol of the specific α 2receptor antagonist RX 821002. The magnitude of pressor response to NA in the LSA was increased by i.v. pretreatment with the ganglion blocker pentolinium (10 mg/kg) and significantly reduced by i.v. pretreatment with the V 1 -vasopressin receptor antagonist dTyr (CH2)5(Me) AVP (50 μg/kg). No pressor response to NA was observed in hypophysectomized rats. The present observation of α 1 -adrenoceptor-mediated pressor responses after local injection of NA confirms earlier evidence of a LSA involvement in central cardiovascular control. Pretreatment with the α 1 -adrenoceptor antagonist WB-4101 did not affect baseline blood pressure or heart rate suggesting no tonic involvement of septal adrenergic mechanisms suggesting a modulatory LSA influence on cardiovascular control.
Limited Effect of Systemic -Blockade on Sympathetic Outflow
Hypertension, 2001
Central -adrenoreceptors may augment sympathetic outflow. We tested the hypothesis that -blockade attenuates central sympathetic outflow by inhibiting central adrenoreceptors. We studied 18 healthy controls (4 female, 14 male; age, 26Ϯ6 years, body mass index, 23Ϯ3 kg/m 2 ). ECG, brachial, and finger arterial blood pressure, muscle sympathetic nerve activity, and respiration were measured continuously before and during complete -blockade. Subjects received a total intravenous dose of 0.21 mg/kg of propranolol in 15 minutes. Spontaneous baroreflex slopes were calculated using the sequence technique (BRSup, BRSdown). The sympathetic baroreflex slope was determined at baseline using phenylephrine and sodium nitroprusside infusions. The subjects underwent cold pressor testing before and during -blockade. The R-R interval increased from 861Ϯ119 ms at baseline to 952Ϯ141 ms during -blockade (PϽ0.01). Blood pressure was 117Ϯ9/65Ϯ8 mm Hg at baseline and 117Ϯ10/67Ϯ8 mm Hg during -Blockade (PϭNS). -Blockade did not affect baroreflex sensitivity (BRSup: 21Ϯ10 versus 28Ϯ11 ms/mmHg, PϽ0.1; BRSdown: 17Ϯ8 versus 20Ϯ8 ms/mmHg, PϭNS). Muscle sympathetic nerve activity increased significantly during -blockade (number of bursts/100 beats: 32Ϯ9 versus 40Ϯ14, PϽ0.05), compared with baseline. However, the operating points of the parasympathetic and sympathetic baroreflex during -blockade were on the baroreflex curves obtained at baseline. -Blockade blunted the heart rate response to cold pressor testing; blood pressure and muscle sympathetic nerve activity responses were similar. Our study demonstrates that propranolol does not cause an acute decrease in sympathetic activity in normotensive young subjects. This, observation is not consistent with an important tonic stimulatory effect of -adrenoreceptors in the brain. (Hypertension. 2001;38:1377-1381.)
Neuroscience Letters, 2006
Injection of noradrenaline (NA) into the lateral cerebral ventricle (i.c.v.) was reported to cause blood pressure increase in unanesthetized rats, blocked by i.v. injection of vasopressin antagonists. We report similar responses to NA injection into the III or IV ventricles, suggesting multiple sites of action for i.c.v. NA. These responses were blocked by i.v. pretreatment with vasopressin antagonist, suggesting a common mediation by vasopressin release into circulation. Selected ventricular spaces were occluded with Nivea ® cream plugs to identify ventricular areas responding to i.c.v. NA. III ventricle or aqueduct occlusions markedly reduced pressor responses to i.c.v. NA. Microinjection of NA into the periaqueductal gray matter (PAG) caused pressor responses that were similar to those of i.c.v. NA, reinforcing the idea of a site of action in the aqueduct. IV ventricle occlusion only partially blocked the response to i.c.v. NA. The results suggest at least two sites of action for i.c.v. NA in unanesthetized rats. A primary site located in the PAG and another on the IV ventricle wall.
Journal of Neuroscience Research, 2008
The periaqueductal gray area (PAG) is a mesencephalic area involved in cardiovascular modulation. Noradrenaline (NA), a neurotransmitter involved in central blood pressure control, is present in the rat PAG. We report here on the cardiovascular effects caused by NA microinjection into the ventrolateral PAG (vlPAG) of unanesthetized rats and the peripheral mechanism involved in their mediation. NA microinjection in the vlPAG of unanesthetized rats evoked dose-related pressor and bradycardiac responses. No significant cardiovascular responses were observed in urethane-anesthetized rats. The pressor response was potentiated by pretreatment with the ganglion blocker pentolinium (5 or 10 mg/kg, intravenously). Pretreatment with the vasopressin antagonist dTyr(CH2)5 (Me)AVP (50 μg/kg, intravenously) blocked the pressor response evoked by the NA microinjection into the vlPAG. Additionally, circulating vasopressin content was found to be significantly increased after NA microinjection in the vlPAG. The results suggest that activation of noradrenergic synapses within the vlPAG modulates vasopressin release in unanesthetized rats. © 2007 Wiley-Liss, Inc.
Archiv für Experimentelle Pathologie und Pharmakologie
1. Coronary vasoconstriction was examined in response to the neuronal release of noradrenaline produced by bilateral carotid occlusion and the infusion of tyramine (5-50 gg/kg/min i. v.) in anaesthetized dogs which had been vagotomized and treated with the ]~-adrenoceptor antagonist propranolol (1.0 mg/kg i.v.). These responses were compared to those produced by the infusion of noradrenaline (0.1-0.5 gg/kg/min i.v.). 2. Similar increases in late diastolic coronary resistance were produced by bilateral carotid occlusion (0.70 + 0.25 mmHg min/ml), and intravenous infusions of tyramine, 20~tg/kg/min (0.70+0.12 mmHg min/ml) and noradrenaline, 0.5 gg/kg/min (0.59 _+ 0.11 mm Hg min/ml). 3. Selective antagonism at eladrenoceptors with prazosin (0.5 mg/kg i.v.) attenuated the coronary constrictor response to bilateral carotid occlusion (0.36 + 0.09 mm Hg min/ml), tyramine (0.12 __% 0.06 mm Hg min/ml) and noradrenaline (0.18 + 0.07 mmHg min/ml). Antagonism at c~2-adrenoceptors with idazoxan (1 mg/kg i.v.) attenuated the coronary vasoconstriction produced by bilateral carotid occlusion (0.30 + 0.06 mmHg min/ml), tyramine (0.17 + 0.08 mm Hg min/ml) and noradrenaline (0.12 _+ 0.03 mm Hg min/ml). Combined antagonism at both cq-and e2-adrenoceptors with prazosin and idazoxan abolished the responses to bilateral carotid occlusion, tyramine and noradrenaline. 4. These results show that coronary vasoconstriction produced by either neuronally released or exogenous noradrenaline is mediated by both cqand c~2-adrenoceptors. It appears that in the coronary resistance vessels of the dog postjunctional al-and c~2adrenoceptors are both innervated by sympathetic nerves.
Cardiovascular effects of noradrenaline microinjected into the insular cortex of unanesthetized rats
Autonomic Neuroscience, 2011
The insular cortex (IC) has been reported to be involved in central cardiovascular control. In the present study, we investigated the cardiovascular responses evoked by microinjection of noradrenaline into the IC as well as the central and peripheral mechanisms involved in their mediation. Microinjection of noradrenaline into the IC (3, 7, 10, 15, 30 and 45 nmol/100 nL) caused long-lasting dose-related pressor and bradycardiac responses. The cardiovascular responses evoked by 15 nmol of noradrenaline were blocked by IC pretreatment with WB4101 or 5-methyl-urapidil, selective α 1 -adrenoceptor antagonists. IC pretreatment with either the selective α 2 -adrenoceptor antagonists RX821002 or the β-adrenoceptor antagonist propranolol did not affect noradrenaline cardiovascular responses. Noradrenaline cardiovascular responses were mimicked by microinjection of the selective α 1 -adrenoceptor agonist phenylephrine into the IC, thus reinforcing the idea that α 1 -adrenoceptors mediate cardiovascular responses to noradrenaline microinjected into the IC. The pressor response to noradrenaline microinjection was potentiated by i.v. pretreatment with the ganglion blocker pentolinium and inhibited by i.v. pretreatment with the selective V 1 -vasopressin receptor antagonist dTyr(CH 2 ) 5 (Me)AVP. The bradycardiac response to noradrenaline microinjection into the IC was abolished by pretreatment with either pentolinium or the V 1 -vasopressin receptor antagonist, indicating its reflex origin. In conclusion, our results suggest that pressor response evoked by microinjection of noradrenaline into the IC involve the activation of IC α 1 -adrenoceptors to cause the release of vasopressin into the circulation.
Cellular and Molecular Neurobiology, 2012
We have previously reported that stimulation of alpha-1 adrenoceptors by noradrenaline (NA) injected into the lateral septal area (LSA) of anaesthetized rats causes pressor and bradycardic responses that are mediated by acute vasopressin release into the circulation through activation of the paraventricular nucleus (PVN). Although the PVN is the final structure of this pathway, the LSA has no direct connections with the PVN, suggesting that other structures may connect these areas. To address this issue, the present study employed c-Fos immunohistochemistry to investigate changes caused by NA microinjection into the LSA in neuronal activation in brain structures related to systemic vasopressin release. NA microinjected in the LSA caused pressor and bradycardic responses, which were blocked by intraseptal administration of a-1 adrenoceptor antagonist (WB4101, 10 nmol/200 nL) or systemic V-1 receptor antagonist (dTyr(CH2)5(Me)AVP, 50 lg/kg). NA also increased c-Fos immunoreactivity in the prelimbic cortex (PL), infralimbic cortex (IL), dorsomedial periaqueductal gray (dmPAG), bed nucleus of the stria terminalis (BNST), PVN, and medial amygdala (MeA). No differences in the diagonal band of Broca, cingulate cortex, and dorsolateral periaqueductal gray (dlPAG) were found. Systemic administration of the vasopressin receptor antagonist dTyr AVP (CH2)5(Me) did not change the increase in c-Fos expression induced by intra-septal NA. This latter effect, however, was prevented by local injection of the alpha-1 adrenoceptor antagonist WB4101. These results suggest that areas such as the PL, IL, dmPAG, BNST, MeA, and PVN could be part of a circuit responsible for vasopressin release after activation of alpha-1 adrenoceptors in the LSA.