Vasorelaxant effects of oxpentifylline and theophylline on rat isolated aorta.
The mechanism of the relaxation response of rat aorta to the phosphodiesterase inhibitors oxpentifylline and theophylline was studied. Oxpentifylline induced a greater vasorelaxation response in the intact strips than in those without endothelium. The endothelium-dependent relaxation response to oxpentifylline was inhibited by nitro-L-arginine but not by indomethacin, and the endothelium-independent relaxation response was potentiated by the combination with isoprenaline but not sodium nitroprusside. Theophylline induced a similar relaxation response in vascular strips with and without endothelium. The relaxation response to theophylline was not inhibited by indomethacin or nitro-L-arginine in intact strips, but was potentiated by combination with isoprenaline or sodium nitroprusside in the denuded strips. These results suggest that the two phosphodiesterase inhibitors oxpentifylline and theophylline induce vasorelaxation by different mechanisms. Oxpentifylline can induce both endothelium-dependent relaxation, which is probably mediated by an endothelium-derived relaxing factor, and endothelium-independent relaxation, which may be due to an inhibitory action on phosphodiesterase of vascular smooth muscle. In contrast, theophylline can induce endothelium-independent relaxation alone, without modulation by the endothelium.
Marukawa
S
S
Department of Intensive Care Unit, Hyogo College of Medicine, Japan.
Hatake
K
K
Wakabayashi
I
I
Hishida
S
S
D000818:Animals; D001013:Aorta, Thoracic; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D010431:Pentoxifylline / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D013806:Theophylline; D007545:Isoproterenol; D010431:Pentoxifylline