The effect of basic fibroblast growth factor on coronary vascular tone in experimental hypercholesterolemia in vivo and in vitro.

OBJECTIVE

To determine whether bFGF causes coronary vasoconstriction in experimental hypercholesterolemia in association with endothelial dysfunction.

METHODS

We infused 0.02 microgram/kg per min bFGF into the left anterior descending artery of anesthetized pigs (n = 5) before and after 10 weeks of a high-cholesterol diet. The coronary artery diameter (CAD) was measured by quantitative angiography and the coronary blood flow (CBF) was calculated using coronary-flow Doppler measurements. In additional in-vitro studies, epicardial arteries from normal and hypercholesterolemic pigs were exposed to cumulative concentrations of bradykinin (10(-11)-10(-6) mol/l) after precontraction with 10(-6) mol/l endothelin-1. Cumulative concentrations of bFGF (10(-13)-10(-8) mol/l) were added to other vessels with and without prior contraction with 10(-5) mol/l PGF2 alpha. Similar in-vitro studies were performed using rings from which the endothelium had been removed.

RESULTS

In vivo, intracoronary administration of bFGF increased the CBF by 33 +/- 33% and the CAD by 12 +/- 5% at baseline, but reduced the CBF by 45 +/- 8% and the CAD by 14 +/- 6% after 10 weeks of a high-cholesterol diet. In vitro, the endothelium-dependent vasorelaxation in response to bradykinin was attenuated significantly in coronary arteries from hypercholesterolemic pigs (P < 0.05). Cumulative concentrations of bFGF exerted no effect on the coronary epicardial tone both in normal (with and without endothelium) and in hypercholesterolemic pigs.

CONCLUSIONS

Acute administration of intracoronary bFGF caused coronary vasodilatation under steady-state conditions and vasoconstriction under diet-induced hypercholesterolemia. In vitro, bFGF did not affect the coronary epicardial tone. These findings suggest that the coronary vasoactive properties of bFGF may be exerted indirectly and are affected by the functional integrity of the endothelium.