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

Recent evidence has indicated that the mitogen platelet‐derived growth factor (PDGF) can act acutely to regulate arterial tone. In this study we demonstrate that the BB isoform of PDGF (PDGF‐BB) can cause endothelium‐independent relaxation of rabbit isolated mesenteric arteries. In endothelium‐denuded arteries, PDGF‐BB (40 p M –8.0 n M ) caused concentration‐dependent relaxation of noradrenaline‐induced tone. The relaxation to PDGF‐BB was abolished by a cyclo‐oxygenase inhibitor, indomethacin (10 μ M ) and by the PDGF receptor‐associated tyrosine kinase inhibitor, tyrphostin AG1295 (50 μ M ), but not by N G ‐monomethyl‐ L ‐arginine ( L ‐NMMA, 200 μ M ), an inhibitor of nitric oxide (NO) synthase. PDGF‐BB (4.0 n M ) significantly increased the release of prostacyclin (PGI 2 ) in endothelium‐denuded arteries. Exogenously applied iloprost (1 μ M ), a stable analogue of PGI 2 , relaxed the endothelium‐denuded artery. PDGF‐BB (4.0 n M ) significantly increased the cyclic AMP content. In the absence of Ca 2+ , PDGF‐BB (4.0 n M ) failed to relax the artery, and the release of PGI 2 was almost completely suppressed. In addition, the release of PGI 2 by PDGF‐BB (4.0 n M ) was significantly reduced in the presence of endothelium. The effect of endothelium was eliminated by L ‐NMMA (200 μ M ) and PGI 2 release increased. 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 Ca 2+ and tyrosine phosphorylation of the PDGF receptor, and is attenuated by endothelium‐derived NO.British Journal of Pharmacology (2000) 131 , 1546–1552; doi: 10.1038/sj.bjp.0703771