Abstract 221: Lost Adiponectin-induced Renal Sodium Excretion in Hypertension

Abstract

Obesity related hypertensive patients are often with impaired sodium excretion. However,the mechanisms are not clear. Adipocytes secrete numerous hormones, among which adiponectin is an important one. Adiponectin KO mice developed hypertension when maintained on a high-salt diet. In hypertensive patients, the plasma adiponectin levels are lower; there is relationship between lower serum adiponectin and new-onset hypertension.We hypothesize that adiponectin induces natriuresis and diuresis, the impaired adiponectin-induced sodium excretion might be involved in hypertension. Our present study found the expressions of both adiponectin (AdipoR1 and AdipoR2) receptor in kidney from Wistar-Kyoto rats. Infusion of adiponectin via supra-renal artery induces natriuresis and diuresis in Wistar-Kyoto rats. Treatment with adiponectin inhibited Na + -K + -ATPase activity in renal proximal tubule cells of Wistar-Kyoto rats. The inhibitory effect was mainly via AdipoR2 receptor, because the siRNA of AdipoR2, not AdipoR1,completely blocked the effect of adiponectin. In the presence of inhibitor for AMPK (compound C) or eNOS (L-NAME), the inhibitory effect of adiponectin on Na+-K+-ATPase activity was blocked, indicating AMPK-NO pathway is involved in the signaling pathway. In spontaneous hypertension rats, adiponectin-induced natriuresis and diuresis were lost;similarly, the inhibitory effect on Na+-K+-ATPase activity was also lost in renal proximal tubule cells of spontaneously hypertension rats. The impaired adiponectin effect might be ascribed to lower AdipoR2 expression in renal proximal tubule cells od spontaneously hypertension rats, because transfected with AdipoR2 reversed the inhibitory effect on Na+-K+-ATPase activity. These datas suggested that adiponection, via AdipoR2,induces natriuresis and diuresis; the impaired adiponectin function might be involved in the pathogenesis of hypertension.