Effects of endothelin-1 on optic nerve head blood flow in cats.
We determined the effects of endothelin-1 on optic nerve head (ONH) blood flow in anesthetized cats. Endothelin-1 (50-2500 pmol) injected into the vitreous produced a dose-related and sustained decrease (22 +/- 6% by 500 pmol and 36 +/- 11% by 2500 pmol) in the ONH blood flow. Blood pressure (BP) and heart rate (HR) remained, however, unchanged. In contrast, intravenous (i.v.) injected endothelin-1 (0.004-0.4 nmol kg-1) produced a dose-related and short-lasting increase in the ONH blood flow; its maximum increase by 0.4 nmol kg-1 was 135 +/- 34%. Endothelin-1, at 0.4 nmol kg-1, i.v., produced a transient decrease followed by a more sustained increase in BP, but had no remarkable effect on HR. The increase in ONH blood flow by i.v. injection of endothelin-1 was abolished by N(G)-nitro-L-arginine methyl ester (L-NAME, 5 mg kg-1 min-1, i.v.). The suppression of blood flow by L-NAME was reversed by the addition of L-arginine (50 mg kg-1 min-1). Pressor responses to endothelin-1 (0.4 nmol kg-1, i.v.) were augmented in the presence of L-NAME, but reversed in combination with L-arginine. These findings suggest that i.v. injection of endothelin-1 causes NO release from endothelial cells which increases ONH blood flow, whereas intravitreal injection of endothelin-1 decreases ONH blood flow by its vasoconstrictive effect. Different populations of ET receptors on vascular smooth muscles or endothelial cells would reflect the opposing effects of endothelin-1.
Nishimura
K
K
Research Laboratories, Santen Pharmaceutical Co., Ltd., Osaka, Japan.
Riva
C E
CE
Harino
S
S
Reinach
P
P
Cranstoun
S D
SD
Mita
S
S
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D019332:Endothelin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007267:Injections; D007275:Injections, Intravenous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009900:Optic Nerve / Q000098:blood supply*; D012039:Regional Blood Flow / Q000187:drug effects; D014822:Vitreous Body
D019332:Endothelin-1; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester