Hypoxia inhibits myogenic reactivity of renal afferent arterioles by activating ATP-sensitive K+ channels

Recent findings implicate K+ channels as important modulators of myogenic tone and possible mediators of the vasodilatory effects of hypoxia. In the present report, we examined the effects of hypoxia on myogenic vasoconstriction of renal afferent arterioles. Using the in vitro perfused hydronephrotic rat kidney model, we observed precisely graded decreases in arteriolar diameter when renal perfusion pressure was increased. Normal myogenic reactivity was observed over PO2 levels of 150 to 80 mm Hg. Reducing PO2 to 60, 40, and 30 mm Hg resulted in a significant progressive inhibition of myogenic reactivity. At ~20 mm Hg, myogenic vasoconstriction was essentially abolished, whereas the vasoconstriction induced by 30 mmol/L KCl was unaffected. The addition of 1.0 μmol/L glibenclamide completely restored myogenic vasoconstriction during hypoxia. In contrast, 1.0 mmol/L tetraethylammonium did not alter the effects of hypoxia. To investigate the relation between hypoxia-induced vasodilation and smooth muscle oxidative phosphorylation, we monitored changes in arteriolar levels of reduced NADH during exposure to hypoxia. Arterioles preconstricted by elevated pressure were optically isolated for simultaneous monitoring of vessel diameter and NADH fluorescence (360-nm excitation, 450-nm emission). Reducing perfusate PO2 from 150 to 20 mm Hg resulted in progressive loss of myogenic tone with no change in arteriolar-NADH. These findings indicate that lowering PO2 within a physiological range attenuates myogenic reactivity of the renal afferent arteriole by causing the activation of ATP-sensitive K+ channels. However, hypoxia elicits these effects without inducing a concomitant increase in arteriolar NADH, suggesting that K(ATP) channel activation occurs without a reduction in oxidative production of ATP within the arteriolar smooth muscle cell.