CORRECTION OF HYPERTENSION BY NORMALIZATION OF ENDOTHELIAL LEVELS OF FIBROBLAST GROWTH-FACTOR AND NITRIC-OXIDE SYNTHASE IN SPONTANEOUSLY HYPERTENSIVE RATS

Acidic and basic fibroblast growth factors (FGFs) share a wide range o f diverse biological activities. To date, low levels of FGF have not b een correlated with a pathophysiologic state. We report that blood ves sels of spontaneously hypertensive rats are shown to be associated wit h a marked decrement in endothelial basic FGF content. This decrement correlates both with hypertension and with a decrease in the endotheli al content of nitric oxide synthase. Restoration of FGF to physiologic al levels in the vascular wall, either by systemic administration or b y in vivo gene transfer, significantly augmented the number of endothe lial cells with positive immunostaining for nitric oxide synthase, cor rected hypertension, and ameliorated endothelial-dependent responses t o vasoconstrictors. These results suggest an important role for FGFs i n blood pressure homeostasis and open new avenues for the understandin g of the etiology and treatment of hypertension.