Vasodilator effect of nicorandil on retinal blood vessels in rats.
We examined the effect of nicorandil on retinal blood vessels in rats in vivo. Male Wistar rats (8 to 10 weeks old) were anaesthetised with thiobutabarbital (120 mg/kg, intraperitoneal). Fundus images were captured with a digital camera that was equipped with a special objective lens. Diameters of retinal blood vessels were measured with a personal computer. Nicorandil (1-300 microg kg(-1) min(-1), intravenous [i.v.]) increased diameters of retinal blood vessels and decreased systemic blood pressure in a dose-dependent manner. Both responses to nicorandil were attenuated by glibenclamide (20 mg/kg, i.v.), an adenosine triphosphate (ATP)-dependent K(+) (K(ATP)) channel blocker. On the other hand, indomethacin (5 mg/kg, i.v.), a cyclooxygenase inhibitor, attenuated the vasodilation of retinal blood vessels, but not depressor response, to nicorandil and sodium nitroprusside. Pinacidil (1-300 microg kg(-1) min(-1), i.v.), a K(ATP) channel opener, also dilated retinal blood vessels and decreased systemic blood pressure. The responses to pinacidil were prevented by glibenclamide, but not by indomethacin. The vasodilation of retinal arteriole, but not depressor response, to sodium nitroprusside (1-30 microg kg(-1) min(-1), i.v.), a nitric oxide donor, was attenuated by indomethacin. These results suggest that nicorandil dilates retinal blood vessels through opening of K(ATP) channels and production of prostaglandins that are probably generated by nitric oxide.
Ogawa
Naoto
N
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
Saito
Maki
M
Mori
Asami
A
Sakamoto
Kenji
K
Kametaka
Sokichi
S
Nakahara
Tsutomu
T
Ishii
Kunio
K
D000704:Analysis of Variance; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D020108:Nicorandil / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D020110:Pinacidil / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012171:Retinal Vessels / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D020030:Nitric Oxide Donors; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; D009599:Nitroprusside; D020108:Nicorandil; D009569:Nitric Oxide; D020110:Pinacidil; D005905:Glyburide; D007213:Indomethacin