Cardiovascular, renal, and endocrine responses to intravenous endothelin in conscious dogs

Endothelin is a recently discovered vasoconstrictor peptide that is synthesized in certain vascular endothelial cells. We have identified the cardiovascular, renal, and hormonal responses that can be elicited in conscious dogs by intravenous administration of endothelin at rates of 10 and 30 ng.kg-1.min-1 for 60 min (0.24 and 0.72 nmol.kg-1/1-h infusion). Each dose of endothelin increased total peripheral resistance, arterial pressure, and left atrial pressure and decreased heart rate and cardiac output. Hematocrit increased by 4.8% (NS) and 22.9% (P less than 0.01) in response to the lower and higher infusion rates, respectively. Urinary sodium excretion, urine osmolality, and osmolar clearance decreased and free water clearance increased. The lower dose of endothelin decreased plasma norepinephrine and increased plasma atriopeptin. The higher dose increased plasma levels of vasopressin, renin, aldosterone, norepinephrine, epinephrine, and atriopeptin. The higher infusion rate of the peptide caused one or more brief vomiting episodes in four of five dogs. Although it is not yet known whether endothelin is a circulating hormone, it is clear that this peptide is capable of causing profound cardiovascular, renal, and endocrine alterations in conscious dogs. The possible relevance of these observations to physiological processes and to pathological conditions such as hypertension remains to be established.