Effects of endothelin on arterial pressure and venous tone in intact and hexamethonium-treated conscious rats.

The dose-response effects of the potent vasoconstrictor peptide endothelin on mean arterial pressure (MAP), heart rate (HR), and mean circulatory filling pressure (MCFP), an index of body venous tone, were investigated in conscious and unrestrained, intact rats as well as in rats continuously infused with the ganglionic blocker hexamethonium. The dose of hexamethonium selected was that which reduced the reflex tachycardia induced by i.v. injections of acetylcholine by 50%. In intact rats and rats pretreated with hexamethonium, i.v. injections of endothelin caused dose-dependent increases in MAP and decreases in HR. Low doses of endothelin did not affect MCFP while the highest dose in the intact rat, and the two highest doses in hexamethonium-treated rats, caused small but significant increases in MCFP. Our results suggest that endothelin has small effects on body venous tone in contrast to its effectiveness in raising arterial pressure.