Intravenously administered vasodilatory prostaglandins increase retinal and choroidal blood flow in rats.
We established an experimental system for measuring blood flow in the rat fundus and examined whether intravenously administered vasodilatory prostaglandins (PGE(1), PGE(2), and PGI(2)), 8-(4-chlorophenylthio)-cAMP (a cAMP analogue), and nicardipine (a Ca(2+)-channel blocker) increase fundus blood flow (FBF). Under artificial ventilation, rats were injected with tetrodotoxin (50 microg/kg, i.v.) to eliminate any nerve activity and prevent movement of the eye. After tetrodotoxin, the rats were infused with norepinephrine (0.3 - 0.5 microg . kg(-1) . min(-1)) and epinephrine (2.7 - 4.5 microg . kg(-1) . min(-1)) simultaneously to maintain adequate systemic circulation. We found that intravenous infusion of PGE(1) (2 - 10 microg . kg(-1) . min(-1)), PGE(2) (3 - 30 microg . kg(-1) . min(-1)), and PGI(2) (1 - 10 microg . kg(-1) . min(-1)) increased the FBF in a dose-dependent manner. The vasodilatory PGs decreased arterial pressure, whereas they did not affect heart rate. Like vasodilatory PGs, 8-(4-chlorophenylthio)-cAMP (30 micromol/kg, i.v.) increased FBF and decreased arterial pressure. While infusion of nicardipine (0.3 - 3 microg . kg(-1) . min(-1)) produced comparable depressor responses with those to vasodilatory PGs and the cAMP analogue, it did not increase FBF. These results suggest that vasodilatory PGs and cAMP act more selectively than Ca(2+)-channel blockers on retinal/choroidal blood vessels. Therefore, the vasodilatory PGs might be considered to be possible candidates for the therapeutics to treat disorders of retinal/choroidal circulation.
Mori
Asami
A
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Saito
Maki
M
Sakamoto
Kenji
K
Nakahara
Tsutomu
T
Ishii
Kunio
K
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002829:Choroid / Q000098:blood supply* / Q000187:drug effects; D000242:Cyclic AMP / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012160:Retina / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D011453:Prostaglandins; D014665:Vasodilator Agents; D013779:Tetrodotoxin; D009529:Nicardipine; D011464:Epoprostenol; D000242:Cyclic AMP; D000527:Alprostadil; D015232:Dinoprostone