Platelet-derived growth factor causes endothelium-independent relaxation of rabbit mesenteric artery via the release of a prostanoid

1 Recent evidence has indicated that the mitogen platelet-derived growth fa ctor (PDGF) can act acutely to regulate arterial tone. In this study we dem onstrate that the BE isoform of PDGF (PDGF-BB) can cause endothelium-indepe ndent relaxation of rabbit isolated mesenteric arteries. 2 In endothelium-denuded arteries, PDGF-BB (40 pM-8.0 nM) caused concentrat ion-dependent relaxation of noradrenaline-induced tone. The relaxation to P DGF-BB was abolished by a cyclooxygenase inhibitor, indomethacin (10 muM) a nd by the PDGF receptor-associated tyrosine kinase inhibitor, tyrphostin AG 1295 (50 muM), but not by NG-monomethyl-L-arginine (L-NMMA, 200 muM), an in hibitor of nitric oxide (NO) synthase. 3 PDGF-BB (4.0 nM) significantly increased the release of prostacyclin (PGI (2)) in endothelium-denuded arteries. Exogenously applied iloprost (1 muM), a stable analogue of PGI(2) relaxed the endothelium-denuded artery. PDGF-B B (4.0 nM) significantly increased the cyclic AMP content. 4 In the absence of Ca2+, PDGF-BB (4.0 nM) failed to relax the artery, and the release of PGI(2) was almost completely suppressed. In addition, the re lease of PGI(2) by PDGF-BB (4.0 nM) was significantly reduced in the presen ce of endothelium. The effect of endothelium was eliminated by L-NMMA (200 muM) and PGI(2) release increased. 5 These data indicate that in rabbit mesenteric arteries, PDGF-BB can evoke endothelium-independent relaxation by stimulating the synthesis of PGI(2). The PDGF-BB-induced prostaglandin synthesis is dependent on both Ca2+ and tyrosine phosphorylation of the PDGF receptor,and is attenuated by endothel ium-derived NO.