Characterization of neurohormonal changes following the production of the benign and malignant phases of two-kidney, two-clip Goldblatt hypertension.
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.
D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D002395:Catecholamines / Q000502:physiology*; D004195:Disease Models, Animal; D004285:Dogs; D004837:Epinephrine / Q000097:blood; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006974:Hypertension, Malignant / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D006978:Hypertension, Renovascular / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D009479:Neuropeptides / Q000502:physiology*; D009638:Norepinephrine / Q000097:blood; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
D000959:Antihypertensive Agents; D002395:Catecholamines; D006584:Hexamethonium Compounds; D009479:Neuropeptides; D000804:Angiotensin II; D001127:Arginine Vasopressin; D018738:Hexamethonium; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D000803:Angiotensin I; D002216:Captopril; D012083:Renin; D009638:Norepinephrine; D004837:Epinephrine