Effect of diet-induced obesity on BKCa function in contraction and dilation of rat isolated middle cerebral artery

Abstract

This study examined the effect of diet-induced obesity on the functional role of large-conductance Ca2+-activated K+ channels (BKCa) in rat middle cerebral arteries. Male Sprague-Dawley rats were fed a control (chow) or high-fat diet for 16-20weeks. Diet-induced obesity decreased maximum bradykinin-induced dilation of isolated, pressurized (80mmHg) arteries, but vasodilation induced by sodium nitroprusside (SNP) was unaltered. Responses to bradykinin and SNP in arteries from both control and obese rats were abolished by combination of the nitric oxide synthase (NOS) and guanylate cyclase (sGC) inhibitors L-NAME (100μmol/L) and ODQ (10μmol/L) respectively, or by the BKCa blocker iberiotoxin (IBTX, 0.1μmol/L). Vasodilation induced by the PAR2 agonist SLIGRL in arteries from control-diet rats was abolished by L-NAME/ODQ, but unaffected by IBTX. Obesity greatly reduced the inhibitory effect of L-NAME/ODQ on SLIGRL-induced dilation, whereas IBTX alone now inhibited responses to SLIGRL. Neither obesity nor IBTX altered the responsiveness of the arteries to vasoconstrictors 5-hydroxytryptamine (5-HT) or angiotensin II (Ang II). Obesity had variable effects on the functional role of BKCa in the middle-cerebral artery depending upon the agent used to stimulate the channel, reflecting the variety of mechanisms by which BKCa may be activated.