Increased oxidative metabolism in renal tubules from spontaneously hypertensive rats

Abstract

Genetic hypertension in the rat is associated with abnormal renal function. This may be due to systemic hypertension or to intrinsic alterations in the kidney. Therefore, we examined intrinsic rates of oxidative metabolism in renal cortical tubules isolated from spontaneously hypertensive rats (SHR) and age-matched normotensive controls (WKY) before, during, and after the development of hypertension. We examined tubule function in SHR and WKY treated with antihypertensive agents to block the development of hypertension. During the early phase of hypertension (ages 7-8 wk), SHR tubules have intrinsic rates of oxygen consumption that are 15-25% greater than that of WKY. Ouabain-sensitive rates of oxygen consumption, an index of sodium entry, and Na+-K+-ATPase activity were not increased by 17%. Reduction of blood pressure with drugs did not abolish these differences in oxidative metabolism. Addition of exogenous arachidonic acid (1 microM) did reduce the metabolic differences between 8-wk-old SHR and WKY tubules. Norepinephrine (1 microM) had a greater stimulatory effect on oxygen consumption rates in tubules from hypertensive SHR. The relationship of these metabolic differences to the development of hypertension remains unclear.