Possible role of the endothelium on the vascular response to prostaglandin E2 in rat femoral arterial preparations in vivo and in vitro.
The mode of action of prostaglandin E2 was investigated on the rat femoral arterial vascular bed in vivo and on the isolated femoral artery in vitro. In in vivo preparations, prostaglandin E2 (0.01-0.3 microgram), as well as acetylcholine (0.01-0.3 microgram) and nicardipine (0.1-3 micrograms), administered into the femoral artery (i.a.), elicited a dose-dependent increase (vasodilatation) in femoral blood flow, without markedly influencing systemic blood pressure or heart rate. The vasodilator response to prostaglandin E2 was not affected by i.v. pretreatment with atropine (0.5 mg/kg), propranolol (0.5 mg/kg), glibenclamide (20 mg/kg) or NG-monomethyl-L-arginine (100 mg/kg), whereas it was significantly attenuated, like that to acetylcholine, by i.a. infusion of methylene blue. However, methylene blue did not affect the vasodilator response to nicardipine even at a dose sufficient to attenuate the responses to prostaglandin E2 and acetylcholine. In isolated femoral arterial strips, prostaglandin E2 (3 x 10(-8) - 3 x 10(-4) M), phenylephrine (3 x 10(-8) - 1 x 10(-4) M) and U46619 (1 x 10(-9) - 1 x 10(-6) M) induced a concentration-dependent vasoconstriction. The vasoconstrictor responses to prostaglandin E2 and phenylephrine were significantly potentiated by removal of the endothelium and by the presence of methylene blue (3 microM) or NG-monomethyl-L-arginine (100 microM), whereas those to U46619 remained unaffected in the same conditions. The present results indicate that the endothelium may play a role in the vascular response to prostaglandin E2.
Takanashi
H
H
Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D002747:Chlorpropamide / Q000494:pharmacology; D019806:Cromakalim; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005263:Femoral Artery / Q000187:drug effects*; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007261:Infusions, Intra-Arterial; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009529:Nicardipine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine
D001578:Benzopyrans; D011450:Prostaglandin Endoperoxides, Synthetic; D011758:Pyrroles; D019806:Cromakalim; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001285:Atropine; D001120:Arginine; D011433:Propranolol; D009529:Nicardipine; D015232:Dinoprostone; D007545:Isoproterenol; D000109:Acetylcholine; D005905:Glyburide; D008751:Methylene Blue; D002747:Chlorpropamide