Antihypertensive Polar Renomedullary Lipid, A Semisynthetic Vasodilator

SUMMARY Two types of biologically active lipids have been derived from renomedullary tissue. One is neutral (ANRL) and the other polar (APRL). Upon a bolus I.V. injection, APRL causes a rapid decline of the mean arterial pressure (MAP) after a single injection and a prolonged depressor effect after either multiple injections or an infusion. APRL became evident when a reduction procedure, using the Vitride reagent, was used. Thus, APRL is likely a semisynthetic product. Multiple chemical and enzymatic manipulations suggest that APRL is a glycerophosphate with the active acyl group in Position 2. The acute and prolonged effects of APRL may be due to different components in its mixture. Hemodynamic studies indicate that both the acute and prolonged effect of APRL causes vasodilatation with minimal or no tachycardia. Visualization of the microcirculation reveals arteriolar dilatation. Larger bolus doses also cause a decrease in cardiac output (CO) that could be due to venodilatation. A negative i DO tropic effect has not been ruled out for APRL. This seems unlikely as indicated by minimal change in CO as MAP is lowered substantially (lower doses), no change in right atrial pressure, no direct effect on isolated atria] myocardium and no change in the index of myocardial contractility. It is suggested that the depression of CO with higher doses may be due to venodilatation. Preliminary studies fail to reveal acute toxiclty. APRL is a powerful vasodilator.