Mechanism of antihypertensive effect of potassium depletion in renovascular hypertension

C. R. Nolan, S. L. Linas

Research output: Contribution to journalArticlepeer-review

Abstract

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 < 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 < 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 < 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 II 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 < 0.005) with K. In summary, the decrease in vascular responsivity to ANG II in KD rats with renovascular hypertension is the result of a postreceptor abnormality. The postreceptor event is masked by ANG II-induced downregulation of receptor binding and is mediated by cellular K depletion.

Original languageEnglish (US)
Pages (from-to)24/5
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume255
Issue number5
StatePublished - 1988

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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