Basic Fibroblast Growth Factor Dilates Rat Pial Arterioles

Abstract

Summary: Basic fibroblast growth factor (bFGF) is a polypeptide that promotes the survival and differentiation of brain neurons, glia, and endothelial cells. It has been shown recently that intravenously administered bFGF lowers blood pressure by systemic vasodilation; this ef fect is mediated, in part, by nitric oxide (NO)-dependent mechanisms. In the current study, we directly evaluated the effect of bFGF on pial arterioles of pentobarbital anesthetized Sprague-Dawley rats (n = 18) using the closed cranial window technique. Basic FGF (5-200 ng/ ml) produced dose-dependent vasodilation; maximal ves sel diameter (-120% of control) was reached at 100 ng/ Basic fibroblast growth factor (bFGF) is an 18-kDa polypeptide found within the mammalian brain with potent multipotential trophic effects on brain cells. In vitro, bFGF promotes the survival and out growth of a wide variety of neurons from embryonic rat brain and supports the survival and proliferation of brain glia and capillary endothelial cells (Gospo darowicz et al., 1986a;Pettman et al., 1985; Wa licke, 1988). In the intact brain, bFGF is localized to neurons and glial cells, whereas the high-affinity bFGF receptor (fig) is widely localized on both neu rons as well as non-neuronal cells (Emoto et al., 1989;Finklestein et al., 1988;Gomez-Pinilla et al., 1992;Woodward et al., 1992). In particular, the density of bFGF receptors is high in vascular brain structures (including circum ventricular organs and choroid plexus), most likely due to their localization Abbreviations used: ANOVA, analysis of variance; bFGF, ba sic fibroblast growth factor; BSA, bovine serum albumin; CGRP, calcitonin gene-related peptide; EAA, excitatory amino acids; L-NAME, ,vo-nitro-L-arginine methyl ester; PBS, phosphate buffered saline. 70ml. No vasodilation was found when bFGF was heat in activated, or preincubated with blocking antibody. Moreover, bFGF-induced vasodilation was attenuated by coadministration of the NO synthase inhibitor �-nitro L-arginine methyl ester (L-NAME), consistent with an NO-dependent mechanism. These results suggest that bFGF may play an important role in the regulation of cerebrovascular tone and cerebral blood flow.

Vasodilatory Effect of Basic Fibroblast Growth Factor in Isolated Rat Cerebral Arterioles: Mechanisms Involving Nitric Oxide and Membrane Hyperpolarization.

“…The topical application of bFGF (5 to 200 ng/ml) produced dose-dependent arteriolar dilation to a maximum of 120% of control in rats. 20) Superfusion of 25 g bFGF in rabbits, which is a higher concentration than that used in rats, increased cortical blood flow by 33%. 19) Together, these findings suggest that bFGF, which is widely distributed in the neonatal and adult central nervous system, is important in the regulation of both cortical and intracerebral microcirculation.…”

“…25) An acute hypotensive effect was observed in rats and rabbits, establishing a nonmitogenic function of bFGF as an affector of vascular tone. 5) Subsequent in vivo studies have shown that bFGF increased cortical blood flow 19) or dilated pial arterioles 20) and rat basilar arteries, 15) suggesting that bFGF may contribute to the regulation of pial microcirculation 19,20) and the cerebral posterior circulation. 15) bFGF is found constitutively in neurons and astroglia [8][9][10] with receptors found in cerebral blood vessels, 26) suggesting that bFGF may contribute to cerebrovascular regulation.…”

“…15) bFGF is found constitutively in neurons and astroglia [8][9][10] with receptors found in cerebral blood vessels, 26) suggesting that bFGF may contribute to cerebrovascular regulation. 20) bFGF is of clinical interest because of its ability to reduce cerebral infarction. 1,12,22) However, the mechanism of bFGFinduced vasodilation is not completely understood.…”

“…Previous studies have suggested that endotheliumderived nitric oxide (EDNO) is central in the bFGFinduced vasodilatory process, 5,15,20) but may not be solely responsible. 5) Electrophysiological studies have revealed that membrane hyperpolarization of SMCs, which is likely to be mediated by endothelium-derived hyperpolarizing factor (EDHF), is associated with EDNO-dependent vasodilation.…”

Neuroprotection in experimental stroke with targeted neurotrophins

“…30 bFGF is widely distributed in neuronal and non-neuronal tissues and has additional effects of mitogenic activity and vasodilatation. 31,32 There is a growing body of evidence that bFGF is neuroprotective in a variety of preclinical studies, and data in this area had been reviewed by Ay and associates. 33 It should be noted that bFGF is a cationic peptide that undergoes transport across the BBB at a modest rate via absorptive-mediated transcytosis after intravenous administration.…”