Sodium-potassium pump activity in reduced renal-mass hypertension

We have previously reported that ouabain-sensitive “Rb uptake, a measure of Na⁺-K⁺pump activity, is decreased in blood vessels of animals with several low renin, and probably volumedependent models of hypertension likely due to the action of a circulating sodium transport inhibitor. In this paper we summarize a detailed study of these and other related parameters in a model known to be volume expanded, reduced renal-mass hypertension in rats. We measured cardiovascular muscle cell Na⁺-K⁺pump activity in control normotensive and experimental hypertensive reduced renalmass rats, assayed super nates of boiled plasma from these rats for presence of a circulating Na⁺transport inhibitor and studied the effects of anteroventral third ventricle (AV3V) lesions and central sympathectomy (by intraventricular injection of 6-hydroxydopamine) on development of reduced renal-mass hypertension, and on vascular Na⁺-K⁺pump activity and level of circulating Na⁺transport inhibitors). We also measured the effect of dietary sodium restriction on reduced renal-mass hypertension, cardiovascular muscle cell Na⁺-K⁺pump activity and level of the circulating Na⁺transport inhibitor. Compared to the normotensive control rats, the experimental hypertensive rats had increased extracellular fluid volume, decreased plasma renin activity, increased level of a circulating Na⁺transport inhibitor, decreased vascular Na⁺-K⁺pump activity (even after in vitro chemical sympathectomy) and decreased cardiac microsomal Na⁺-K⁺-ATPase activity. Pump suppression and development of hypertension were temporally associated. Both AV3V lesions and central sympathectomy prevented development of reduced renal-mass hypertension, inhibition of vascular Na⁺-K⁺pump activity, and appearance of a circulating Na⁺transport inhibitor. Withdrawal of saline reversed reduced renal-mass hypertension as well as vascular pump suppression and increased levels of a circulating pump inhibitor. These data support the hypothesis that inhibition of cardiovascular muscle cell Na⁺-K⁺pump activity by a circulating Na⁺transport inhibitor that is released from or influenced by the AV3V area of the brain plays an important role in the mechanism of some types of low renin experimental hypertension.