Enhanced microvascular relaxations to vegf and bfgf in chronically
-ischemic porcine myocardium.
Sellke, Frank W., Steven Y. Wang, Alon Stamler, John J. Lopez, Jian
Li, Jianyi Li, Michael Simons.
Division of Cardiothoracic Surgery (FWS, SYW, AS, JYL), Department
of Surgery, Cardiovascular Division (JL, JJL, MS), Department of
Medicine, Beth Israel Hospital; and the Harvard Medical School,
Boston, MA 02215
APStracts 3:0072H, 1996.
Changes in the vascular responses to VEGF and bFGF in chronically
ischemic myocardium have not been investigated. Ameroid constrictors
were placed on the proximal left circumflex (LCx) artery of 7
Yorkshire pigs. Seven to 9 weeks later, myocardial blood flow in the
collateral-dependent LCx region was reduced compared to that in the
normally-perfused left anterior descending (LAD) region. Both growth
factors elicited significant relaxations of coronary microvessels.
Relaxations to both VEGF and bFGF were inhibited in the presence of
either NGnitro-L-arginine or genistein, suggesting that the
relaxations are through the tyrosine kinase-mediated release of
endothelium-derived nitric oxide. Microvascular relaxations to both
VEGF or bFGF were significantly greater in vessels harvested from the
collateral-perfused LCx region compared to those taken from the
normally-perfused LAD region. However, relaxation to the endothelium
-dependent vasodilator adenosine 5' diphosphate, which does not
operate through a tyrosine kinase receptor, was reduced in the
collateral-perfused region compared to the normally perfused
territory, suggesting a possible link of tyrosine kinase to the
enhanced relaxations to VEGF and bFGF in collateral-perfused coronary
microvessels. Northern analysis showed increased expression for both
VEGF receptors (flk-1, flt-1) as well as the FGFR-1 receptor in the
collateral-perfused region compared to that in the normally perfused
region. This suggests that the increased relaxation responses to VEGF
and bFGF in the ischemic myocardium may be related to increased gene
expression of the respective tyrosine kinase receptors.
Received 20 November 1995; accepted in final form 6 February
1996.
APS Manuscript Number H1084-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 14 February 96