Microvascular effects of endothelin-1.

In the present study we examined the microvascular actions of endothelin (ET-1) in rat cremaster arterioles. Pentobarbital (35 mg/kg) anesthetized, five to six week old rats were prepared for in vivo observation and measurement of microvascular control dimensions and changes in diameter, in response to the topical administration of ET-1 (1 x 10(-11) to 5 x 10(-10) M). The effects of ET-1 were determined before and after the administration, by suffusion upon the cremaster muscle, of either indomethacin (IND, 10 micrograms/ml) or methylene blue (MB, 5 microM). Third order arterioles; 13-25 microns in diameter, were selected for study. The administration of ET-1 evoked a biphasic response of cremaster arterioles, an initial small, fleeting increase in diameter (14 to 26%) followed by a dose-dependent, longer lasting decrease in diameter (20 to 77%). The administration of either MB or IND had no effect on the arteriolar dilator and constrictor responses to ET-1. These results suggest that ET-1 is more potent a constrictor than dilator agent in this vascular bed and that the dilator component of the response is not mediated by either prostaglandins or EDRF. By virtue of its actions and potency, we conclude that ET may be an important factor in the regulation of vascular tone and local blood flow.