Hemodynamic and vascular activity of LY127210, a new vasodilator, in anesthetized spontaneously hypertensive rats: comparison with hydralazine.

We used microsphere techniques to determine cardiac output and tissue blood flows in chloralose-anesthetized spontaneously hypertensive rats treated with LY127210 (10 mg/kg, i.p.), hydralazine (2 mg/kg, i.p.), or saline. LY127210 decreased blood pressure, systemic vascular resistance, heart rate and left ventricular end-diastolic pressure. Regional vascular resistance fell in kidney, cerebral cortex, ileum and skin, and blood flow decreased in skin, and cerebral cortex. After hydralazine, blood pressure, systemic resistance and left ventricular end-diastolic pressure also decreased, but heart rate increased. Regional vascular resistance decreased in the kidney, cerebral cortex, ileum, myocardium and skeletal muscle, and blood flow was either maintained or increased in these tissues. Unlike LY127210, hydralazine decreased blood flow and increased vascular resistance in the skin. Thus, LY127210 reduces blood pressure in hypertensive rats by reducing vascular resistance, although about 1/3 of the fall in pressure was attributed to a decrease in cardiac output. Since heart rate, stroke volume and skin resistance did not increase, LY127210 might also interfere with baroreflex mechanisms.