vasopressin--1-(1-mercaptocyclohexaneacetic-acid)-2-(o--methyl-l-tyrosine)-8-l-arginine- and Hypertension--Renovascular

This study was designed to elucidate how central and peripheral arginine vasopressin (AVP) interacts with the sympathetic nervous system and the renin-angiotensin system to maintain blood pressure in two-kidney, one-clip hypertensive rabbits. We recorded renal sympathetic nerve activity (RSNA) in the conscious state as an index of sympathetic nervous system function. The changes in mean arterial pressure, heart rate, and RSNA were recorded continuously for 60 minutes after intravenous administrations of captopril (2.5 mg/kg) and nicardipine (3.2 micrograms.kg-1.min-1) in eight identical rabbits. Despite equivalent reductions in mean arterial pressure (10 +/- 1 mm Hg), the increase in RSNA was significantly larger with captopril than that with nicardipine, and the plasma concentration of AVP was elevated (from 100% to 255 +/- 24%) with captopril. Mean arterial pressure was reduced, and RSNA was increased by intravenous infusion of AVP antagonist d(CH2)5Tyr(Me)AVP (n = 8), whereas vertebral artery infusion of the antagonist (n = 6) did not change RSNA. During central and peripheral infusions of AVP antagonist, RSNA was exaggerated by blood pressure reduction with nicardipine as well as with captopril. Increases in RSNA induced by captopril and nicardipine were larger by central infusion of AVP antagonist than by intravenous infusion. The decrease in mean arterial pressure by captopril (30 +/- 4 mm Hg) in eight sinoaortic-denervated hypertensive rabbits was larger than that in hypertensive rabbits with intact baroreflex. These data suggest that compensatory activation of RSNA was revealed by central and peripheral attenuation of AVP and that the sympathetic nervous system became the most important mechanism for blood pressure maintenance in the absence of AVP. The interaction of AVP with the sympathetic nervous system may be independent of the state of the renin-angiotensin system, since the exaggeration of RSNA by AVP antagonist was qualitatively the same with nicardipine as with captopril. In conscious renal-hypertensive rabbits, AVP in the central nervous system played a substantial role when blood pressure was reduced, although it did not contribute to blood pressure maintenance in the basal condition.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Blood Pressure; Captopril; Clonidine; Disease Models, Animal; Female; Hypertension, Renovascular; Kidney; Nicardipine; Norepinephrine; Rabbits; Renin-Angiotensin System; Sympathetic Nervous System

The neurohormonal contribution to high blood pressure was investigated in 9 conscious two-kidney, two-clip Goldblatt (2K2C) hypertensive dogs during evolution of the benign and malignant phases after application of bilateral renal clips (BRC). Serial measurements were taken of the plasma renin activity (PRA), plasma angiotensin I-immunoreactivity (Ang I-ir), plasma angiotensin II-ir (Ang II-ir), renin substrate (RS) catecholamines [epinephrine (Epi) and norepinephrine (NE)] and vasopressin (AVP). Immediately after BRC, the elevation of the blood pressure (86 +/- 3 to 110 +/- 3 mmHg, p less than 0.01) was associated with an increase in heart rate (93 +/- 3 to 114 +/- 9 beats/min, p less than 0.01). These hemodynamic changes were accompanied by increases in PRA, Ang I-ir, Ang II-ir, Epi, NE and AVP. The renin angiotensin system was activated throughout the 3 week period following BRC, as indicated by increases in PRA, Ang I-ir and Ang II-ir. Catecholamines were elevated immediately after BRC, followed by a return toward the control values. AVP underwent a slight but not significant elevation after BRC, which was sustained during the 3 weeks. Production of malignant hypertension was affected by occlusion of one of the adjustable renal clips 3 weeks after BRC. A marked elevation of the blood pressure was associated with significant increases in PRA, Ang I-ir, Ang II-ir, Epi, NE and AVP, compared with the pre-occlusion values. In addition, pharmacologic experiments were performed in 6 of 9 dogs. Administration of angiotensin I converting enzyme inhibitor (SQ 14225) reduced the blood pressure both in the benign and malignant phases of 2K2C renovascular hypertension, and a ganglionic blocking agent (hexamethonium) also decreased the blood pressure. However, a specific, vascular acting AVP antagonist failed to reduce the blood pressure significantly. From this study, it seems likely that severe renal ischemia caused by renal clipping caused the activation of the renin-angiotensin and the sympathetic nervous system and elevation of serum vasopressin. However, there are no apparent differences between the benign and malignant phases of renovascular hypertension, except for the marked elevation of neurohormone levels in malignant hypertension.

Topics: Angiotensin I; Angiotensin II; Animals; Antihypertensive Agents; Arginine Vasopressin; Captopril; Catecholamines; Disease Models, Animal; Dogs; Epinephrine; Hexamethonium; Hexamethonium Compounds; Hypertension, Malignant; Hypertension, Renovascular; Neuropeptides; Norepinephrine; Renin; Renin-Angiotensin System; Sympathetic Nervous System

The role of vasopressin (VP) in maintaining blood pressure in malignant two-kidney one-clip Goldblatt hypertension in chronically catheterized conscious rats was investigated by studying the effect of two structurally different VP pressor antagonists. Injections of either 20 micrograms/kg of dPTyr(Me)AVP or 10 micrograms/kg of d(CH2)5Tyr(Me)AVP failed to alter mean arterial pressure or heart rate, although both antagonists completely inhibited the pressor response elicited by exogenous VP. These results suggest, that VP is not involved as a pressor hormone in the maintenance of high blood pressure in this type of experimental hypertension.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Female; Hypertension, Malignant; Hypertension, Renovascular; Rats; Vasopressins