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 +/- 5 vs. K replete 164 +/- 4 mm Hg, P less than 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 (+/- 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 +/- 20 vs. 81 +/- 5 fmol/mg of protein, P less than 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 +/- 13 vs. 93 +/- 7 fmol/mg protein, P less than 0.01) were increased in K depleted cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Linas
S L
SL
Department of Medicine, University of Colorado, Health Sciences Center, Denver.
Marzec-Calvert
R
R
Ullian
M E
ME
O'Brien
R F
RF
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D002478:Cells, Cultured; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D011191:Potassium Deficiency / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System
D000804:Angiotensin II; D009638:Norepinephrine