L-Arginine (>30mg kg-', i.v.), but not D-arginine (300 mg kg-') administered 5 min after unilateral common carotid/middle cerebral artery occlusion increased regional cerebral blood flow (rCBF) within the dorsolateral ischaemic cortex in spontaneously hypertensive rats. L-Arginine (300 mg kg-') increased rCBF from 22 ± 2.7 to 33 ± 4% of baseline as measured by laser-Doppler flowmetry. This increase may explain the ability of L-arginine to reduce infarct size following focal cerebral ischaemia, as reported previously. The mechanism appears to be mediated by nitric oxide since topical L-NAME (1 gM), a nitric oxide synthase inhibitor, decreased pial arteriole calibre from 115 ± 2.2 to 106 ± 0.9% of baseline following L-arginine infusion (300 mg kg-').
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.
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