Hypercapnia-induced cerebral and ocular vasodilation is not altered by glibenclamide in humans

Carbon dioxide is an important regulator of vascular tone. Glibenclamide, a n inhibitor of ATP-sensitive potassium channel (K-ATP) activation, signific antly blunts vasodilation in response to hypercapnic acidosis in animals. W e investigated whether glibenclamide also alters the cerebral and ocular va sodilator response to hypercapnia in humans. Ten healthy male subjects were studied in a controlled, randomized, double-blind two-way crossover study under normoxic and hypercapnic conditions. Glibenclamide (5 mg po) or insul in (0.3 mU.kg(-1).min(-1) iv) were administered with glucose to achieve com parable plasma insulin levels. In control experiments, five healthy volunte ers received glibenclamide (5 mg) or nicorandil (40 mg) or glibenclamide an d nicorandil in a randomized, three-way crossover study. Mean blood flow ve locity and resistive index in the middle cerebral artery (MCA) and in the o phthalmic artery (OA) were measured with Doppler sonography. Pulsatile chor oidal blood flow was assessed with laser interferometric measurement of fun dus pulsation. Forearm blood flow was measured with venous occlusion plethy smography. Hypercapnia increased ocular fundus pulsation amplitude by +18.2 -22.3% (P < 0.001) and mean flow velocity in the MCA by +27.4-33.3% (P < 0. 001), but not in the OA (2.1-6.5%, P = 0.2). Forearm blood flow increased b y 78.2% vs. baseline (P = 0.041) after nicorandil administration. Glibencla mide did not alter hypercapnia-induced changes in cerebral or ocular hemody namics and did not affect systemic hemodynamics or forearm blood flow but s ignificantly increased glucose utilization and blunted the nicorandil-induc ed vasodilation in the forearm. This suggests that hypercapnia-induced chan ges in the vascular beds under study are not mediated by activation of KATP channels in humans.