Effects of endothelin-1 and sarafotoxin S6b on regional hemodynamics in the conscious dog

Abstract

Endothelin, a potent vasoconstrictor, also is capable of producing transient vasodilation in some situations. We examined the changes in regional hemodynamics in response to constant infusions of endothelin-1 (ET-1) at 5, 10, or 20 ng.kg-1.min-1 for 1 h into conscious dogs. The dogs were instrumented with ultrasonic flow probes for measurement of blood flow in the ascending aorta (cardiac output) and in the coronary, mesenteric, renal, and iliac arteries. A compound structurally similar to ET-1, sarafotoxin S6b (S6b), was also infused in identical experiments to determine whether the responses to these two peptides might differ. Basal plasma levels of immunoreactive ET-1 averaged approximately 6 pg/ml. After 55 min of infusion of ET-1 at 5, 10, and 20 ng.kg-1.min-1, plasma immunoreactive ET-1 increased to approximately 55, 130, and 520 pg/ml, respectively. When given at 20 ng.kg-1.min-1, ET-1 increased total peripheral resistance and arterial pressure and decreased cardiac output and heart rate. ET-1 decreased coronary, mesenteric, and renal blood flow but did not change iliac flow. In comparison with ET-1, S6b produced relatively smaller changes in total peripheral resistance, cardiac output, heart rate, and coronary, mesenteric, and renal blood flow. Iliac resistance did not change in response to ET-1, but it increased during infusions of S6b. Similar but less pronounced responses were observed when these peptides were infused at 5 and 10 ng.kg-1.min-1. The regional variability in the hemodynamic response to ET-1 and the difference in regional responses to ET-1 and S6b are consistent with the existence of heterogenous receptor subtypes for these peptides.