EFFECTS OF VASCULAR ENDOTHELIAL GROWTH-FACTOR ON HEMODYNAMICS AND CARDIAC-PERFORMANCE

Vascular endothelial growth factor (VEGF), a major regulator of angiog enesis, has therapeutic benefit in animal models of coronary or limb i schemia. However, the hemodynamic effects of VEGF have not been invest igated. We examined the effects of VEGF on hemodynamics and cardiac pe rformance. Mean arterial pressure (MAP), heart rate (WR), cardiac outp ut, stroke volume, left ventricular (LV) dP/dt, and hematocrit were me asured before and after intravenous injection of VEGF in conscious, in strumented rats. VEGF caused a dose-dependent reduction inMAP and an a ssociated increase in PIR. VEGF (250 mu g/kg) significantly decreased cardiac output and stroke volume without affecting the inotropic state of the left ventricle, as determined by dPicir. VEGF significantly in creased hematocrit, Furthermore, VEGF did not affect contractiiity or HR in the isolated rat heart in vitro. The data suggest that the VEGF- induced decrease in cardiac output is due to reduced stroke volume, wh ich may be caused by a decrease in venous return rather than a direct effect on myocardial contractilitSI. In addition, pretreatment with N- omega-nitro-L-arginine methylester (L-NAME), a nitric oxide (NO) synth ase inhibitor, significantly attenuated the depressor and tachycardic responses to VEGF, suggesting that VEGF-induced hypotension may be med iated by NO.