Interrelationship of Cardiovascular Effects,Plasma Levels of Nicorandil,and Vascular cGMP Formation in Conscious Rats

The relationship between the dual activity of nicorandil (K_ATP channel-opening activity and nitrate-like action), plasma levels, and changes in vascular cGMP levels and cardiovascular parameters was investigated in conscious rats. Nicorandil (3 mg kg^?1, p.o.) was rapidly absorbed and caused a significant reduction in blood pressure, lasting for at least 1 h, increases in heart rate and femoral blood flow, and decreases in femoral vascular resistance. These were entirely abolished by intravenous glibenclamide (20 mg kg^?1). The plasma concentration of nicorandil reached a maximum 30 min after dosing. After administration of nicorandil, a correlation was observed between blood pressure and plasma nicorandil level or femoral vascular resistance. A significant increase (P < 0.05) in the cGMP content of the thoracic aorta occurred 15 min after administration of nicorandil, and persisted for at least 2 h. These results imply that nicorandil induces vasodilatation by opening K_ATP channels in peripheral resistance vessels, leading to overt reduction of blood pressure, but acts on conductance vessels mainly through nitrate-like activity.