Interrelationship of cardiovascular effects, plasma levels of nicorandil, and vascular cGMP formation in conscious rats

J Pharm Pharmacol. 1998 Jun;50(6):661-6. doi: 10.1111/j.2042-7158.1998.tb06902.x.

Abstract

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.

MeSH terms

  • Administration, Oral
  • Animals
  • Blood Pressure / drug effects*
  • Cyclic GMP / metabolism*
  • Glyburide / pharmacology
  • Hypoglycemic Agents / pharmacology
  • Male
  • Niacinamide / analogs & derivatives*
  • Niacinamide / blood
  • Niacinamide / pharmacokinetics
  • Nicorandil
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Vasodilator Agents / blood
  • Vasodilator Agents / pharmacokinetics*

Substances

  • Hypoglycemic Agents
  • Vasodilator Agents
  • Niacinamide
  • Nicorandil
  • Cyclic GMP
  • Glyburide