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. 1984 Jan;73(1):79–86. doi: 10.1172/JCI111209

Mechanism of decreased vascular reactivity to angiotensin II in conscious, potassium-deficient rats.

M S Paller, J G Douglas, S L Linas
PMCID: PMC424972  PMID: 6690484

Abstract

Chronic potassium deficiency in the rat results in a decrease in the pressor sensitivity to exogenous angiotensin II (AII). To define the mechanism of this resistance to AII, studies were performed in conscious rats after 14-21 d of dietary potassium deficiency. The pressor response to graded doses of AII was 50% less in potassium-deficient than control animals. In contrast, the pressor response to graded doses of norepinephrine was preserved in potassium-deficient rats; therefore, the decreased response to AII was not due to a generalized defect in vascular reactivity. Pretreatment with either the converting enzyme inhibitor, teprotide, or the prostaglandin synthesis inhibitor, indomethacin, failed to normalize the response to AII. Thus, neither prior receptor occupancy with endogenous AII nor the presence of vasodilatory prostaglandins caused the decreased AII response in potassium deficiency. Since the pressor response to AII involves angiotensin interaction with its vascular receptor, binding studies of mesenteric artery and uterine smooth muscle AII receptors were performed. Scatchard analysis showed that potassium deficiency resulted in a decrease in binding affinity (50% increase in Kd) in both uterine (6.00 vs. 3.82 nM; P less than 0.05) and vascular (1.39 vs. 0.973 nM; P less than 0.005) smooth muscle. Furthermore, despite increased circulating AII, there was an increase in AII receptor number in potassium-deficient uterine (308 vs. 147 fmol/mg protein; P less than 0.005) and vascular (470 vs. 316 fmol/mg protein; 0.05 less than P less than 0.1) smooth muscle. Although potassium deficiency resulted in alterations in receptor-binding parameters, the changes in binding affinity and number were directionally opposite, so that in potassium deficiency there was either no change or an increase in total AII binding. We conclude that the decrease in angiotensin pressor sensitivity in potassium-deficient rats is mediated by a postreceptor defect since it occurs subsequent to the binding of AII to its vascular smooth muscle receptor.

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Selected References

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