Effects of Endothelin-1 on Optic Nerve Head Blood Flow in Cats

Abstract

ABSTRACT

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 suppresion 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.