• J. Cardiovasc. Pharmacol. · Feb 1999

    Platelet-derived growth factor-induced vasodilatation in mesenteric resistance arteries by nitric oxide: blunted response in spontaneous hypertension.

    • H Takase, B S Oemar, M Pech, and T F Lüscher.
    • Department of Cardiology, Cardiovascular Research, University Hospital Zürich, Switzerland.
    • J. Cardiovasc. Pharmacol. 1999 Feb 1; 33 (2): 223-8.

    AbstractPlatelet-derived growth factor (PDGF) is a potent mitogen for vascular smooth-muscle cells, but its effects on vasomotion remain controversial. Both vasoconstriction and vasodilatation of isolated rat aortic rings have been reported. The effects of PDGF on responses of perfused mesenteric resistance arteries from normotensive Wistar-Kyoto and spontaneously hypertensive rats were studied by using a video dimension analyzer. PDGF receptor messenger RNA (mRNA) expression in endothelial cells isolated from mesenteric arteries of both normotensive and hypertensive rats was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. In both normotensive and hypertensive rats, PDGF-BB concentration-dependently induced vasodilatation (maximal response, 25 +/- 4% and 13 +/- 4% at 10(-8) M, respectively; p < 0.05, normotensive vs. hypertensive rats). Endothelium removal or preincubation with N(omega)-nitro-L-arginine methyl ester, but not indomethacin, inhibited these relaxations, indicating that these vasodilatations are endothelium dependent and mediated by nitric oxide. RT-PCR analysis showed that both PDGF-alpha and -beta receptor mRNAs were present in endothelial cells of the mesenteric arteries of normotensive as well as hypertensive rats. In addition, relaxations induced by both PDGF-AA and -AB were significantly less than those induced by PDGF-BB in both strains, suggesting that vasodilatation is mediated mainly by the PDGF-beta receptor subtype. No vasoconstriction was observed after application of PDGF-BB to both normotensive and hypertensive mesenteric arteries with or without endothelium. In rat mesenteric resistance arteries, PDGF induces endothelium-dependent vasodilatation mediated by nitric oxide. At sites where PDGF is released or locally produced, therefore, the growth factor may participate in regulating vascular tone, and this endothelium-dependent regulation is attenuated in spontaneous hypertension.

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