Hemodynamic actions of intravenous endothelin in rats: comparison with sodium nitroprusside and methoxamine

We investigated hemodynamic actions of endothelin (ET) in conscious rats. Intravenous injections of ET produced dose-dependent biphasic blood pressure (MAP) responses: initial decreases of up to 84 +/- 11 s were followed by increases of up to 1-h duration. Corresponding responses in cardiac output (CO), heart rate, and efferent splanchnic nerve activity were reciprocal to changes in MAP. Mesenteric blood flow showed an immediate and sustained decrease. Compared with equidepressor doses of sodium nitroprusside (NNP), ET produced a markedly different regional hemodynamic response pattern during the initial depressor phase. Compared with equipressor doses of the alpha-adrenoceptor agonist methoxamine, ET produced significantly greater vasoconstriction in hindlimb and renal vascular bed during pressor phase. ET-induced changes in CO were significantly greater than the respective CO responses to NNP and methoxamine in intact animals and following cardiac autonomic blockade with atenolol and methscopolamine. ET has vasodilator and vasoconstrictor properties that induce a unique hemodynamic response pattern on intravenous injection. Persistence of ET-induced changes in CO following cardiac autonomic blockade suggests direct cardiostimulatory actions of the peptide during depressor phase as well as direct cardiodepressant actions during pressor phase.