Article date: December 2000
By: Hideyuki Yamawaki, Koichi Sato, Masatoshi Hori, Hiroshi Ozaki, Hideaki Karaki in Volume 131, Issue 8, pages 1546-1552
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 pM–8.0 nM) caused concentration‐dependent relaxation of noradrenaline‐induced tone. The relaxation to PDGF‐BB was abolished by a cyclo‐oxygenase inhibitor, indomethacin (10 μM) and by the PDGF receptor‐associated tyrosine kinase inhibitor, tyrphostin AG1295 (50 μM), but not by NG‐monomethyl‐L‐arginine (L‐NMMA, 200 μM), an inhibitor of nitric oxide (NO) synthase.
PDGF‐BB (4.0 nM) significantly increased the release of prostacyclin (PGI2) in endothelium‐denuded arteries. Exogenously applied iloprost (1 μM), a stable analogue of PGI2, relaxed the endothelium‐denuded artery. PDGF‐BB (4.0 nM) significantly increased the cyclic AMP content.
In the absence of Ca2+, PDGF‐BB (4.0 nM) failed to relax the artery, and the release of PGI2 was almost completely suppressed. In addition, the release of PGI2 by PDGF‐BB (4.0 nM) was significantly reduced in the presence of endothelium. The effect of endothelium was eliminated by L‐NMMA (200 μM) and PGI2 release increased.
These data indicate that in rabbit mesenteric arteries, PDGF‐BB can evoke endothelium‐independent relaxation by stimulating the synthesis of PGI2. The PDGF‐BB‐induced prostaglandin synthesis is dependent on both Ca2+ and tyrosine phosphorylation of the PDGF receptor, and is attenuated by endothelium‐derived NO.
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 pM–8.0 nM) caused concentration‐dependent relaxation of noradrenaline‐induced tone. The relaxation to PDGF‐BB was abolished by a cyclo‐oxygenase inhibitor, indomethacin (10 μM) and by the PDGF receptor‐associated tyrosine kinase inhibitor, tyrphostin AG1295 (50 μM), but not by NG‐monomethyl‐L‐arginine (L‐NMMA, 200 μM), an inhibitor of nitric oxide (NO) synthase.
PDGF‐BB (4.0 nM) significantly increased the release of prostacyclin (PGI2) in endothelium‐denuded arteries. Exogenously applied iloprost (1 μM), a stable analogue of PGI2, relaxed the endothelium‐denuded artery. PDGF‐BB (4.0 nM) significantly increased the cyclic AMP content.
In the absence of Ca2+, PDGF‐BB (4.0 nM) failed to relax the artery, and the release of PGI2 was almost completely suppressed. In addition, the release of PGI2 by PDGF‐BB (4.0 nM) was significantly reduced in the presence of endothelium. The effect of endothelium was eliminated by L‐NMMA (200 μM) and PGI2 release increased.
These data indicate that in rabbit mesenteric arteries, PDGF‐BB can evoke endothelium‐independent relaxation by stimulating the synthesis of PGI2. The PDGF‐BB‐induced prostaglandin synthesis is dependent on both Ca2+ 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
DOI: 10.1038/sj.bjp.0703771
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