title: Endothelium-derived relaxing factor inhibits norepinephrine contraction of fetal guinea pig arteries.
abstract: As in the adult circulation, the endothelium may play an important role in determining fetal vascular tone. The purpose of this study was to determine the influence of the endothelium on norepinephrine- and phenylephrine-induced contraction of pulmonary and carotid arteries from near-term fetal guinea pigs. Isometric contractions of isolated rings to the cumulative addition of norepinephrine (10(-9)-10(-5) M) were measured before and after 1) endothelium removal, 2) NG-monomethyl-L-arginine (L-NMMA; 10(-4) M) to inhibit endothelium-derived relaxing factor (EDRF), 3) methylene blue (10(-5) M) to inhibit guanylate cyclase, 4) oxyhemoglobin (3 x 10(-6) M) to bind EDRF, and 5) indomethacin (10(-5) M) to inhibit cyclooxygenase. All treatment effects were measured in endothelium-intact segments. The maximal norepinephrine contraction of fetal pulmonary (40 +/- 8% KCl, n = 7) and carotid (13 +/- 7% KCl, n = 7) arteries was much less (P < 0.05) than the maximal contraction to 120 mM KCl. Treatments that inhibit the action of EDRF increased contraction of both fetal pulmonary and carotid arteries. L-NMMA also increased contraction to phenylephrine. Indomethacin had no effect on the contractile responses to norepinephrine of either artery. Thus EDRF inhibits alpha-adrenoceptor-stimulated contraction of fetal pulmonary and carotid arteries and may attenuate the constrictor responsiveness of the fetal circulation in vivo.
authors: Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City 52242.
authors: L P
authors: LP
authors: Thompson
authors: C P
authors: CP
authors: Weiner
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects / Q000196:embryology / Q000502:physiology; D002339:Carotid Arteries / Q000187:drug effects / Q000196:embryology / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005260:Female; D005333:Fetus / Q000098:blood supply*; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D010108:Oxyhemoglobins / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011247:Pregnancy; D011651:Pulmonary Artery / Q000187:drug effects / Q000196:embryology / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine
chemical_list: D010108:Oxyhemoglobins; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D008751:Methylene Blue; D009638:Norepinephrine; D007213:Indomethacin