Use of a specific mesenteric vasodilator peptide, urotensin I, to reduce afterload in the dog

The authors have previously demonstrated that urotensin I, a peptide derived from the urophysis of bony fish, reduced arterial blood pressure of anesthetized dogs by selective dilation of the mesenteric vascular bed. In the present experiments, intravenous infusions of urotensin I produced a sustained increase in cardiac output and decrease in peripheral resistance. The magnitude of the hypotensive response and of reflex effects on the heart appeared to be limited quantitatively by the unique mechanism of action. Coronary artery flow was maintained in spite of a decrease in coronary filling pressure, presumably as a consequence of coronary autoregulation and the increased cardiac output. No direct cardiac effects were observed on close-arterial injection into a coronary artery. An agent with these characteristics which will decrease left ventricle afterload is of interest in the management of myocardial failure and possibly of cardiogenic shock. In dogs in which minimal myocardial injury was produced by injection of thrombin into a coronary artery, intravenous infusions of urotensin I restored minimal but statistically significant elevations in right and left ventricular end-diastolic pressures to preinsult levels.