A comparison of the hemodynamic effects of endothelin-1 and sarafotoxin S6b in conscious rats.

The hemodynamic effects of sarafotoxin S6b (SRT) and endothelin-1 (ET-1) were studied in conscious, freely moving rats. Intravenous bolus administration of ET-1 produced an initial transient depressor response and skeletal muscle (hindquarters) vasodilation. This depressor activity was not observed after i.v. SRT except at a high dose. The initial fall in blood pressure was followed by a sustained pressor response and an increase in total peripheral resistance which were mediated, at least partially, by visceral (mesenteric) and skeletal muscle (hindquarters) vasoconstriction. The durations of the pressor responses and times required to achieve the peak pressor effects (peak time) were greater for ET-1 as compared to SRT. The results of qualitatively similar sustained hemodynamic effects and the strong correlation between the amplitude of the responses to ET-1 and SRT in individual rats suggest that the sustained pressor responses to these peptides are mediated by the same receptors, although the potency was significantly greater for ET-1 than for SRT. Furthermore, the initial depressor and sustained pressor responses appear to be mediated by distinct receptor subtypes inasmuch as the same dose of ET-1 was required for both vasodilator and vasoconstrictor activity but a higher dose of SRT was required to elicit its vasodilator as compared to constrictor effects. Thus, SRT may have relatively lower affinity for receptors mediating its initial hemodynamic responses whereas ET-1 binds with equal affinity to both receptors. These potent and vascular specific hemodynamic actions suggest a role of endothelin in regulating cardiovascular function.