ENDOTHELIAL ATP-SENSITIVE POTASSIUM CHANNELS MEDIATE CORONARY MICROVASCULAR DILATION TO HYPEROSMOLARITY

Coronary arterial occlusion has been shown to increase osmolarity in t he myocardial interstitium. Intracoronary injection of hyperosmolar so lutions reduces coronary vascular resistance. However, the response of coronary microvessels to an abluminal increase in osmolarity is uncle ar, and the underlying mechanism for its vasomotor regulation has not been elucidated. In this regard, porcine coronary arterioles (81 +/- 2 mu m) were isolated, cannulated, and pressurized for in vitro study. Hyperosmolarity (300-345 mosM) was produced by adding D-glucose or D-s ucrose to the extravascular solution. After the arterioles developed a stable vascular tone, a graded vasodilation was observed when glucose or sucrose was incrementally administered. This hyperosmotic vasodila tion was abolished after endothelial removal. Intraluminal administrat ion of KCl (80 mM) or the ATP-sensitive potassium (K-ATP)-channel inhi bitor glibenclamide (1 mu M) to the intact vessels significantly atten uated the hyperosmotic vasodilation. Inhibition of inward rectifier po tassium channels by a low concentration of BaCl2 (10 mu M) did not aff ect vasodilation. However, a high concentration of BaCl2 (100 mu M), w hich has been reported to inhibit K-ATP channels, attenuated the hyper osmotic vasodilation. Iberiotoxin (100 nM), a calcium-activated potass ium (K-Ca)-channel inhibitor had no effect on hyperosmolarity-induced vasodilation. Inhibition of the synthesis of endothelial nitric oxide, prostaglandins, and arachidonic acid metabolites From cytochrome P-45 0 had no effect on hyperosmotic vasodilation. Furthermore, inhibition of vascular smooth muscle K-ATP channels and the large- and small-cond uctance Kc, channels by extraluminal administration of glibenclamide, iberiotoxin, and apamin, respectively, did not alter vasodilation in r esponse to hyperosmolarity. These results indicate that dilation of co ronary arterioles in response to hyperosmotic stimulation requires an intact endothelium. However the response is independent of the release of nitric oxide, prostaglandins, or cytochrome P-450-related endothel ium-derived hyperpolarizing factor and is not a result of activation o f K-ATP and K-Ca channels in vascular smooth muscle. It is suggested t hat the opening of K-ATP channels in vascular endothelium and subseque nt hyperpolarization of that cell type mediate coronary microvascular dilation in response to hyperosmolarity.