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

Platelet-derived growth factor (PDGF) is a potent mitogen for vascular smoo th-muscle cells, but its effects on vasomotion remain controversial. Both v asoconstriction and vasodilatation of isolated rat aortic rings have been r eported. The effects of PDGF on responses of perfused mesenteric resistance arteries from normotensive Wistar-Kyoto and spontaneously hypertensive rat s were studied by using a video dimension analyzer. PDGF receptor messenger RNA (mRNA) expression in endothelial cells isolated from mesenteric arteri es of both normotensive and hypertensive rats was studied by reverse transc riptase-polymerase chain reaction (RT-PCR) analysis. In both normotensive a nd hypertensive rats, PDGF-BB concentration-dependently induced vasodilatat ion (maximal response, 25 +/- 4% and 13 +/- 4% at 10(-8) M, respectively; p < 0.05, normotensive vs. hypertensive rats). Endothelium removal or preinc ubation with N-omega-nitro-L-arginine methyl ester, but not indomethacin, i nhibited these relaxations, indicating that these vasodilatations are endot helium 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 l ess than those induced by PDGF-BB in both strains, suggesting that vasodila tation is mediated mainly by the PDGF-beta receptor subtype. No vasoconstri ction was observed after application of PDGF-BB to both normotensive and hy pertensive mesenteric arteries with or without endothelium. In rat mesenter ic resistance arteries, PDGF induces endothelium-dependent vasodLlatation m ediated by nitric oxide. At sites where PDGF is released or locally produce d, therefore, the growth factor may participate in regulating vascular tone , and this endothelium-dependent regulation is attenuated in spontaneous hy pertension.