Laboratory Investigation

Kidney International (1988) 34, 18–25; doi:10.1038/ki.1988.140

Mechanism of the antihypertensive effect of K depletion in the spontaneously hypertensive rat

Stuart L Linas1, Rochelle Marzec-Calvert1, Michael E Ullian1 and Richard F O'Brien1

1Department of Medicine, University of Colorado, Health Sciences Center, Denver, Colorado, USA

Correspondence: Stuart L Linas MD, Department of Medicine, Box 4000, Denver General Hospital, 777 Bannock Street, Denver, Colorado, 80204, USA.

Received 23 July 1987; Revised 7 December 1987.

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Abstract

Mechanism of the antihypertensive effect of K depletion in the spontaneously hypertensive rat. K depletion reverses hypertension in the SHR (systolic blood pressure: K deplete 122 plusminus 5 vs. K replete 164 plusminus 4 mm Hg, P < 0.001). To determine the role of the renin angiotensin system in the protective effect of K depletion, we performed studies of vascular reactivity in intact SHR and of angiotensin II (Ang II) binding to mesenteric artery particles and vascular smooth muscle cells (VSMC) in culture from SHR. Pressor sensitivity to Ang II (plusminus converting enzyme inhibition) but not norepinephrine was reduced in K depleted SHR. Thus, the decreased vascular reactivity in K depletion was specific for Ang II rather than a generalized defect. Ang II binding and receptor number (Bmax) (156 plusminus 20 vs. 81 plusminus 5 fmol/mg of protein, P < 0.01) were increased in K depleted mesenteric artery particles. Since K depletion and increases in Ang II have both been associated with increased Ang II binding, Ang II binding was measured after bilateral nephrectomy. Despite reduction of plasma renin activity, total binding and Bmax were still increased in nephrectomized K depleted SHR. To determine the specific effect of K depletion independent of Ang II on Ang II binding, studies were performed in mesenteric artery VSMC from SHR grown in culture. VSMC from K replete SHR were grown to confluency in K replete medium and then were incubated in K depleted medium for 24 hours. Binding was saturable, time and temperature-dependent in K replete and K depleted cells. Total binding and Bmax (139 plusminus 13 vs. 93 plusminus 7 fmol/mg protein, P < 0.01) were increased in K depleted cells. The protective effect of K depletion in SHR is mediated by a decrease in vascular responsiveness to Ang II. Since Ang II binding is increased in both K depleted mesenteric arteries and in K depleted VSMC, the decrease in vascular responsiveness is the result of a K depletion-induced post-binding defect.

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