Role of cyclooxygenase in vasodilation of retinal blood vessels induced by bradykinin in Brown Norway rats.
We investigated the role of cyclooxygenase (COX) in bradykinin (BK)-induced vasodilation of retinal blood vessels in Brown Norway rats using a novel in vivo fluorescent fundus imaging technique. Under artificial ventilation, the animals were treated with tetrodotoxin, and the decreased blood pressure and heart rate were adjusted to the normal ranges by infusing pressor agents. Diameters of retinal blood vessels contained in the fluorescent fundus images were measured. Intravenous infusion of BK (1-30 microg/kg/min) increased diameters of retinal blood vessels and decreased blood pressure in a dose-dependent manner. The retinal vasodilator responses to BK were significantly attenuated by treatment with either indomethacin, a non-selective COX inhibitor, or nimesulide, a selective COX-2 inhibitor, but not with SC-560, a selective COX-1 inhibitor. These COX inhibitors failed to affect the depressor responses to BK. Under conditions of nitric oxide (NO) synthase blockade with N(G)-nitro-l-arginine methyl ester, no inhibitory effects of indomethacin on BK-induced vasodilation of retinal blood vessels were observed. These results suggest that the vasodilator effects of BK on retinal blood vessels are partly mediated through a COX-2-dependent pathway in Brown Norway rats. The prostanoid-dependent component of BK-induced retinal vasodilator response seems to be mediated by a mechanism that involves NO.
Kojima
Naoki
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
Nakahara
Tsutomu
T
Ishii
Kunio
K
D000704:Analysis of Variance; D000777:Anesthetics; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003911:Dextrans; D005451:Fluorescein Angiography / Q000379:methods*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D007091:Image Processing, Computer-Assisted; D007262:Infusions, Intravenous; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D017208:Rats, Wistar; D012171:Retinal Vessels / Q000502:physiology*; D013779:Tetrodotoxin; D013997:Time Factors; D014662:Vasoconstrictor Agents; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents
D000777:Anesthetics; D016861:Cyclooxygenase Inhibitors; D003911:Dextrans; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C015219:fluorescein isothiocyanate dextran; D013779:Tetrodotoxin; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D016650:Fluorescein-5-isothiocyanate; D001920:Bradykinin