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

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

To investigate the possible role of vasopressin (VP) in the maintenance of DOC-salt hypertension the effect of two VP pressor antagonists on mean arterial pressure and the pressor responsiveness to exogenous VP were studied in conscious, freely moving rats with malignant DOC-salt hypertension. Intravenous injections of either 20 micrograms/kg of dP Tyr(Me)AVP or 10 micrograms/kg of d(CH2)5Tyr(Me)AVP had no significant effect on mean arterial pressure and heart rate, although both antagonists almost completely abolished the pressor response to VP. Furthermore, the animals with DOC-salt hypertension exhibited decreased pressor responsiveness to exogenous VP. The present findings strongly suggest that VP is not essential as a pressor hormone for maintaining blood pressure in malignant DOC-salt hypertension.

Topics: Animals; Arginine Vasopressin; Desoxycorticosterone; Dose-Response Relationship, Drug; Female; Hypertension, Malignant; Rats; Sodium Chloride; Vasopressins