Function of the Sodium Pump in Vascular Smooth Muscle in Hypertension

Abstract

Considerable evidence, dating back to the observation of Tobian and Binion in 1952 [1], suggests that there may be abnormalities in the function of the sarcolemmal sodium pump in vascular smooth muscle in hypertension. In 1974, Hendrickx and Casteels demonstrated that an electrogenic sodium pump, activated by levels of [K+]0 and inhibited by cardiac glycosides, exists in vascular tissue [2]. At approximately the same time, we reported attenuated arteriolar dilator responses to small local increases in plasma K+ in animals with certain types of experimental hypertension (3,4) and also in certain patients with essential hypertension (5) (Fig. 1). This attenuation suggested inhibition of the sodium pump of the vascular membrane, perhaps by a digitalis-like substance. It is noteworthy that we conducted these investigation in vivo, where we observed arteriolar, rather than conduit artery, function and where the effects of a circulating inhibitor would likely be detected. It is also noteworthy that the attenuated responses appeared to be specific for K+. Thus, we attributed three abnormal responses to functional, rather than structural, abnormalities in the resistance vessels. In 1972, on the basis of this evidence, we proposed the hypothesis that a decreased sarcolemmal sodium-pump activity may underlie the arteriolar vasoconstriction in certain forms of experimental hypertension [3,4]. In 1974, we extended this hypothesis to essential hypertension in man [5].