Mechanism of decreased vascular response to angiotensin II in renal vascular hypertension.
Compared to many forms of hypertension, vascular reactivity to angiotensin II (AII) is decreased in the early phase of two-kidney, one clip (2-K, 1C) renovascular hypertension (RVH). To determine the role of the AII receptor, we examined vascular responsiveness and 125I-AII binding to mesenteric artery membrane fractions after three weeks of 2-K, 1C RVH. Systolic blood pressure was 165 +/- 8 in RVH and 105 +/- 4 mm Hg in controls, P less than 0.001. Plasma renin activity was 4.2 +/- 0.6 in RVH and 1.4 +/- 0.5 ng AI/ml/hr in controls, P less than .001. The pressor response to exogenous AII was reduced by 40% in RVH. Since administration of a single dose of converting enzyme inhibitor (CEI) did not normalize the response to exogenous AII, the decreased reactivity was not caused by receptor occupancy. 125I-AII binding to mesenteric arteries was equal to or greater in RVH than controls at all concentrations of AII. Scatchard analysis revealed an increase in the total number of binding sites (BMAX): 140.8 +/- 6.3 in RVH versus 91.7 +/- 6.5 fmol/mg in controls, P less than 0.01, while the apparent dissociation constant was unchanged. To determine if the increase in circulating AII caused these binding alterations, rats were either treated with CEI for three days; or unilaterally nephrectomized. Both of these manipulations reversed the decrease in vascular responsiveness as well as the increase in receptor number (BMAX = 136 +/- 13.4 in RVH vs. 94 +/- 9.4 fmol/mg in RVH + nephrectomy, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D012083:Renin