VASCULAR ENDOTHELIAL GROWTH-FACTOR VASCULAR-PERMEABILITY FACTOR PRODUCES NITRIC OXIDE-DEPENDENT HYPOTENSION - EVIDENCE FOR A MAINTENANCE ROLE IN QUIESCENT ADULT ENDOTHELIUM

In vitro studies suggest that vascular endothelial growth factor/vascu lar permeability factor (VEGF/VPF) may stimulate release of nitric oxi de (NO) from endothelial cells. To investigate the hemodynamic consequ ences of recombinant VEGF/VPF administered in vivo, recombinant human VEGF/VPF was administered as a bolus dose of 500 mu g to anesthetized (n=6) or conscious (n=5) New Zealand White rabbits, as well as anesthe tized rabbits with diet-induced hypercholesterolemia (HC; n=7). Anesth etized Yorkshire farm pigs (no specific dietary pretreatment) were stu died before and after receiving 500 mu g intravenous (IV; n=5) or intr acoronary (IC; n=5) VEGF/VPF. In anesthetized, normal rabbits, mean ar terial pressure (MAP) fell by 20.5+/-1.4% (P<.05 versus baseline) with in 3 minutes after IV VEGF/VPF. Pretreatment with N-omega-nitro-L-argi nine caused a significant inhibition of VEGF/VPF-induced hypotension. In conscious, normal rabbits, VEGF/VPF produced a consistent though le sser reduction in MAP. The fall in MAP induced by VEGF/VPF in anesthet ized, HC rabbits (21.5+/-2.5% from baseline) was no different from tha t observed in normal anesthetized rabbits. In pigs, both TV and IC adm inistration of VEGF/VPF produced a prompt reduction in MAP. Heart rate increased, while cardiac output, stroke volume, left atrial pressure, and total peripheral resistance all declined to a similar, statistica lly significant degree in both IV and IC groups. Epicardial echocardio graphy disclosed neither global nor segmental wall motion abnormalitie s in response to VEGF/VPF. We conclude that (1) VEGF/VPF-stimulated re lease of NO, previously suggested in vitro, occurs in vivo; (2) this f inding suggests that functional VEGF/VPF receptors are present on quie scent adult endothelium, consistent with a maintenance function for VE GF/VPF, which may include regulation of NO; and (3) the preserved resp onse of HC rabbits suggests that endothelial cell receptors for VEGF/V PF are spared in the setting of hypercholesterolemia.