The Potential Involvement of the Kca Channel in Nitric Oxide Mediated Coronary Vasodilation
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The objective of this investigation was to determine if the nitric oxidecyclic GMP mechanism of vasodilation is physiologically connected to the KCa channel in the coronary arterial circulation of the rabbit. The potential involvement of this channel in vasodilation mediated by the nitric oxidecyclic GMP mechanism could provide information concerning the development of future anti-anginal therapies. Using eighteen New Zealand White rabbits, charybdotoxin, a KCa channel blocker, was administered between two identical nitroglycerine dose response tests to produce coronary vasodilation. Control rabbits received an infusion of saline between the nitroglycerine dose response tests. Systemic hemodynamics, including heart rate, arterial pressure and left ventricular myocardial contractility (LV +dP / dt max) were monitored throughout each experiment. A doppler flow probe was placed on the epicardial surface of the heart directly above a major coronary artery to determine blood flow to the region distal to the probe. Nitroglycerine (0.3, 1, 3, 10 µg/kg) dose-dependently increased the percent change in peak coronary flow both prior to saline infusion and post-saline infusion. There were no significant differences between the sequential dose response curves before versus after infusion of saline. Percent elevation in coronary flow increased with increasing doses of nitroglycerine prior to charybdotoxin, but this effect was attenuated after infusion of charybdotoxin. The responses to 0.3, 1, 3 and 10 f.lg/kg of nitroglycerine decreased (by 17+ 9, 23+ 8, 21+ 9, and 21+ 50/0), respectively, (Mean + SEM, n=9). Basal hemodynamics were not significantly different before and after infusions of saline or charybdotoxin. Thus, these results suggest that the nitric oxide-cyclic GMP mechanism of vasodilation may be physiologically connected to the KCa channel. However, further in vitro and in vivo investigations are necessary to support these results and to determine the precise mechanism by which KCa channel opening may contribute to arterial relaxation.