Hypoxia and Adenosine Inhibit Myogenic Reactivity by Activating ATP-Sensitive Potassium Channels
Potassium channels have been demonstrated to modulate myogenic vasoconstriction (1) and are suggested to mediate the vasodilatory effects of hypoxia (2). We have recently demonstrated that hypoxia inhibits the pressure-induced renal afferent arteriolar vasoconstriction. This effect of hypoxia is reversed by 1.0 µM glibenclamide, suggesting that hypoxia inhibits myogenic reactivity by activating ATP-sensitive K channels (3). Activation of this glibenclamide-sensitive vasodilatory mechanism occurred at pO2 levels as high as 60 torr and was not associated with a concurrent elevation in reduced nicotinamide (NADH) arteriolar autofluoresence (3). These observations suggest that hypoxia-induced activation of Katp channels is not mediated by a reduction in arteriolar smooth muscle oxidative phosphorylation. Since these findings could be explained by an indirect coupling of hypoxia to vascular smooth muscle Katp channels (e.g., mediated by released autacoids), we have examined the effects of adenosine, adenosine-receptor blockade and cyclooxygenase inhibition on myogenic reactivity and on the vasodilatory response to hypoxia. Our findings suggest that although adenosine also elicits glibenclamidesensitive vasodilation in this model, hypoxia-induced vasodilation is not prevented by adenosine receptor blockade or cyclooxygenase inhibition. We suggest that during hypoxia, ATP-sensitive K channels are activated through a mechanism independent of adenosine, prostaglandin synthesis or reductions in oxidative production of ATP within the smooth muscle cell. The present article summarizes these findings. Portions of this article have been adapted with permission from reference #3.
KeywordsAtrial Natriuretic Peptide Adenosine Receptor KATP Channel Myogenic Response Myogenic Tone
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