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J Pharmacol Exp Ther. 1989 Sep;250(3):1125-31.

Effects of endothelin on regional blood flows in squirrel monkeys.

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  • 1F. Hoffmann-La Roche Ltd., Basle, Switzerland.


Endothelin is a newly described potent vasoconstrictor produced by endothelial cells. The aim of the present study was to evaluate the effects of i.v. injection of human endothelin on regional blood flows (RBFs) and hemodynamic parameters in nonhuman primates. For this purpose, in a first series of experiments, anesthetized squirrel monkeys were instrumented with Doppler flow-probes in order to measure RBF continuously in the renal, mesenteric and iliac vascular beds. Endothelin at 0.03 and 0.1 microgram/kg produced no effect. After 0.3 and 1 microgram/kg, renal and mesenteric blood flow decreased, but iliac blood flow increased transiently. With 3 micrograms/kg all the three vascular beds were constricted. In the kidney, blood flow was almost abolished and the effect of endothelin sustained for up to 2 hr and more. In a second series of experiments, radioactive microspheres were used to measure RBFs in most organs 3 to 4 min after endothelin (0.3, 1 and 3 microgram/kg), or after vehicle alone. Endothelin induced a dose-dependent increase in systemic vascular resistance and increase in mean arterial blood pressure. The vasoconstrictor effect was selective for some vascular beds. The splanchnic vascular bed (except stomach) was most affected, with a 96% decrease in renal and splenic blood flow after 3 micrograms/kg of endothelin. The coronary blood flow decreased by 46% after 3 micrograms/kg, with a greater effect in subepicardium than subendocardium. In contrast, the blood flow to the brain and stomach was not decreased by endothelin. We conclude that endothelin is a potent vasoconstrictor in squirrel monkeys selective for some vascular beds.

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