Effects of porcine and rat endothelin and an analog on blood pressure in the anesthetized cat

Arterial responses to a wide range of doses of porcine and rat endothelin and a monocyclic analog were compared in the anesthetized cat. Injections of the porcine peptide in doses of 0.01-0.1 nmol/kg i.v. decreased systemic arterial pressure in a dose-related manner, whereas doses of 0.3 and 1 nmol/kg i.v. elicited biphasic responses. The rat peptide, in doses of 0.03-1 nmol/kg i.v., also decreased arterial pressure in a dose-related fashion, whereas injection at 3 nmol/kg i.v. caused a biphasic response. With both peptides the biphasic response was characterized by an initial short-lived decrease followed by a secondary sustained increase in pressure. The monocyclic porcine analog in doses of 3-30 nmol/kg i.v. had no significant effect on arterial pressure. Both peptides increased cardiac output, and changes in peripheral vascular resistance in response to both peptides were not altered by sodium meclofenamate. These data suggest that arterial depressor responses to porcine and rat endothelin are similar and dose-dependent. However, the porcine peptide has 3-fold greater pressor activity in the cat. The lack of effect with the monocyclic porcine analog suggests that the two disulfide linkages are necessary for activity.