Mechanism of antihypertensive effect of potassium depletion in renovascular hypertension.
K depletion (KD) prevents the development of hypertension in two-kidney, one-clip renovascular, hypertension [mean arterial pressure: 110 +/- 5 (KD) vs. 142 +/- 3 mmHg in potassium replete (KR); P less than 0.001]. The protective effect of KD is associated with a 60% decrease in angiotensin II (ANG II) pressor responsiveness and a 40% decrease in ANG II binding to mesenteric artery particles from rats with renovascular hypertension (receptor number 117 +/- 16 in KD vs. 165 +/- 14 fmol/mg protein in KR, P less than 0.05). To determine whether decreases in binding could account for decreases in ANG II pressor responsivity, we measured ANG II binding after bilateral nephrectomy or sustained administration of converting-enzyme inhibitor. Both maneuvers resulted in increases in binding, such that total binding and receptor number were greater than in comparably treated KR rats; e.g., after nephrectomy, receptor number was 215 +/- 26 in KD vs. 98 +/- 12 fmol/mg protein in KR, (P less than 0.01). Despite increased binding, the pressor response to ANG II in KD rats, which were nephrectomized or treated with converting-enzyme inhibitor, was still reduced by 50% compared with comparably treated KR rats. To determine whether the decreased ANG II pressor responsivity of KD was caused by cellular K depletion or to increases in ANG H induced by KD, we administered K to KD, ANG II-deficient rats. ANG II pressor responsivity increased, and total binding and receptor number decreased (KD, ANG II- deficient 246 +/ 22 fmol/mg protein; KD, ANG II-deficient + K 91 +/ 16 fmol/mg protein; P less than 0.005) with K.(ABSTRACT TRUNCATED AT 250 WORDS)
Nolan
C R
CR
Department of Medicine, University of Colorado Health Sciences Center, Denver 80204.
Linas
S L
SL
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D006978:Hypertension, Renovascular / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D009392:Nephrectomy; D011191:Potassium Deficiency / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000378:metabolism; D012083:Renin / Q000097:blood
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D002216:Captopril; D012083:Renin