Effect of ouabain on arteriolar responses to norepinephrine in chronic, benign, volume-expanded hypertension

We have reported increases in ouabain-sensitive Rb+ uptake by freshly excised conduit arteries from volume-expanded Dahl salt-sensitive (S) rats and also from rats with chronic (4 to 6 weeks), benign (serum creatinine less than 1.4 mg%) one-kidney, one clip ( 1K1C ) hypertension on high NaCl intake. To assess in vivo arteriolar function in this latter model, and a role for putative circulating ouabain-like factors, we perfused the maximally vasodilated (nitroprusside, 0.015 mg/ml limb blood), vascularly isolated, innervated hindlimb vascular beds of chloralose-anesthetized, water- or saline-drinking 1K1C hypertensive rats with their own blood at 1 ml/min, and measured limb responses to i.a. norepinephrine 0.004 to 128 micrograms, before and during local infusion of ouabain (achieving 2.5 X 10(-5) M in limb blood). Complete dose-response curves in eight 1K1C hypertensive rats were steeper and higher than those in five uninephrectomized (1K) normotensive control rats. However, threshold and ED50 were unchanged. Thus, alterations in the curve in the hypertensive rats represented only structural vascular changes. Ouabain evoked a leftward shift of the dose-response curve in an additional 18 1K1C hypertensive rats and 13 1K normotensive controls. In the hypertensive rats as compared to the controls, there were trends for increases, rather than decreases, in the ouabain-induced shift of the curve. Shifts in 14 rats with chronic 2K1C hypertension did not differ from those in the 1K1C hypertensive rats. Together, these studies in chronic, presumably volume-expanded, low-renin hypertension unaccompanied by renal insufficiency provide no evidence for physiologically significant inotropic effects of circulating ouabain-like pump inhibitor.