Endothelium-derived relaxing factor inhibits norepinephrine contraction of fetal guinea pig arteries.
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.
Thompson
L P
LP
Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City 52242.
Weiner
C P
CP
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
D010108:Oxyhemoglobins; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D008751:Methylene Blue; D009638:Norepinephrine; D007213:Indomethacin