Effects of endothelin-1 on optic nerve head blood flow in cats

We determined the effects of endothelin-l on optic nerve head (ONH) blood flow in anesthetized cats. Endothelin-l (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-l (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-l, 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-l was abolished by N-G-nitro-L-arginine methyl ester (L-NAME, 5 mg kg(-1) min(-1), i.v.). The suppresion of blood flow by L-NAME was reversed by the addition of L-arginine (50 mg kg(-1) min(-1)). Presser responses to endothelin-l (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-l causes NO release from endothelial cells which increases ONH blood flow, whereas intravitreal injection of endothelin-l 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.