Systemic and regional effects of endothelin in rabbits: effects of endothelin antibody

1. The effects of porcine endothelin-1 (10(-12)-5 x 10(-10) mol/kg) on arterial blood pressure (BP) and the renal, mesenteric and carotid blood flow (BF), and the effects of endothelin-1 antibody were studied in rabbits. 2. Endothelin-1 caused a sustained increase in BP. The renal, mesenteric and carotid BF were decreased dose-dependently by endothelin-1. The approximate half-maximal effective values (ED50) were 5.5 x 10(-11), 8.6 x 10(-11) and 2.0 x 10(-10) mol/kg for renal, mesenteric and carotid BF respectively. Compared with carotid BF, the renal and mesenteric BF responses were significantly more sensitive to endothelin-1. 3. Combined administration of endothelin-1 and its antibody showed a significant inhibition of the BP and renal BF responses. However, endothelin-1 antibody alone did not change either BP, renal BF, mesenteric BF or carotid BF in vivo. 4. The present results demonstrate that endothelin is a potent vasoconstrictor in vivo. However, circulating endothelin may not contribute to the control of BF and BP. The role of endothelin as a local modulator of the vascular tone remains to be investigated.