Interrelationship of cardiovascular effects, plasma levels of nicorandil, and vascular cGMP formation in conscious rats.
The relationship between the dual activity of nicorandil (KATP 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 KATP channels in peripheral resistance vessels, leading to overt reduction of blood pressure, but acts on conductance vessels mainly through nitrate-like activity.
Central Research Laboratories, Chugai Pharmaceutical Co., Ltd, Tokyo, Japan.
K
K
Sakai
M
M
Akima
S
S
Kamachi
M
M
Moriyasu
S
S
Kitajima
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006152:Cyclic GMP / Q000378:metabolism*; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D020108:Nicorandil; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014665:Vasodilator Agents / Q000097:blood / Q000493:pharmacokinetics*
D007004:Hypoglycemic Agents; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D006152:Cyclic GMP; D005905:Glyburide