![]() 8 However, the roles of K Ca channel activation in cardioplegic arrest (CP) and reperfusion-related microvascular dysfunction in human coronary resistance arterioles and the regulatory properties of these K Ca channels in this vascular bed have little been investigated. 4 Recently, we found that bradykinin preconditioning of coronary microvasculature in isolated rabbit hearts undergoing cardioplegic arrest was mediated in part by the activation of K Ca channels. 5 - 7 The vasodilatory influence of EDHF is believed predominant in smaller arterioles.ĮDHF has been proposed to dilate the coronary arteries through opening of calcium-activated potassium channels (K Ca) in endothelial and smooth muscle cells. 1 - 3 These observations have prompted addition to cardioplegic solutions of nitric oxide donors, exogenous prostacyclin, and EDHF agonists in attempts to attenuate ischemia/reperfusion-mediated endothelial dysfunction. 4 Impaired endothelial synthesis and release of nitric oxide, prostacyclin, and EDHF associated with cardioplegic ischemia and reperfusion may contribute to microvascular endothelial dysfunction. 1 - 3 Endothelium has been found to release 3 major endothelium-dependent relaxing factors: nitric oxide, prostacyclin, and endothelium-dependent hyperpolarization factor (EDHF). Microvascular endothelial dysfunction and altered vascular reactivity often occur after ischemic arrest and cardiopulmonary bypass, although cardioplegia has been routinely used for the protection of the myocardium against ischemic injury during cardiac surgery. The total polypeptide levels of BK Ca, IK Ca, and SK Ca and the expression of IK Ca mRNA were not altered post-CP reperfusion. Endothelial denudation significantly diminished NS309-induced vasodilatation and abolished substance P- or adenosine 5′ diphosphate-induced relaxation ( P<0.05), but had no effect on relaxation induced by either NS1619 or sodium nitroprusside. In contrast, relaxation responses to the activator of large conductance K Ca channels (BK Ca), NS1619 (10 -5 M), and to the endothelium-independent vasodilator, sodium nitroprusside (10 -4 M), were unchanged pre- and post-CP reperfusion (n=8/group). Post-CP reperfusion relaxation responses to the activator of intermediate and small conductance K Ca channels (IK Ca/SK Ca), NS309 (10 -5 M), and to the endothelium-dependent vasodilators, substance P (10 -8 M) and adenosine 5′diphosphate (10 -5 M), were significantly reduced compared with pre-CP responses ( P<0.05, n=8/group). ![]() ![]() ![]() We also examined expression and localization of K Ca channel gene products in the coronary microvasculature using reverse transcriptase-polymerase chain reaction, immunoblot, and immunofluorescence photomicroscopy. In vitro relaxation responses of precontracted arterioles (80 to 180 μm in diameter) in a pressurized no-flow state were examined in the presence of K Ca channel activators/blockers and several other vasodilators. Human atrial tissue was harvested before CP from a nonischemic segment and after CP from an atrial segment exposed to hyperkalemic cold blood CP (mean CP time, 58 minutes) followed by 10-minute reperfusion.
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