MECHANISMS UNDERLYING THE CORONARY VASODILATION IN THE ISOLATED PERFUSED HEARTS OF RATS SUBMITTED TO ONE WEEK OF HIGH CARBON MONOXIDE EXPOSURE IN VIVO

Abstract

We examined the possible mechanisms for carbon monoxide (CO)-induced effects in hearts isolated from Wistar rats exposed for 1 wk to 530 ppm CO. They were treated by daily intraperitoneal injections of either methylene blue (10 mg/kg), glibenclamide (3 mg/kg), or apamin (125 nmol/kg), known to inhibit vasodilatory mechanisms. Hearts were excised, cannulated, and retrogradely perfused through the coronary artery, using the Langendorff method with a constant perfusion pressure. After stabilization, we investigated the degree of resistance to an in vitro transient global low-flow ischemia. Oneweek CO exposure induced a significant increase in hematocrit and a cardiomegaly, which were not affected by any of these drugs. An enhancement of coronary flow was observed concomitantly with a decrease in ischemic contracture after CO exposure. However, no improvement of contractile recovery was noted. Since methylene blue did not interact with the CO effects, a cGMP signaling pathway can be excluded. On the contrary, as glibenclamide and to a greater extend apamin blocked the vasodilatory effects of CO, we conclude that K + channels may be involved in these CO effects.