Role of cyclic nucleotides in relaxation of fetal lamb ductus arteriosus.
Although prostaglandin E1 is used to dilate the constricted ductus arteriosus in infants with cyanotic heart disease, the mechanism is unknown. To test the hypothesis that the cyclic nucleotides adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) play a role in relaxation, isolated rings of the ductus arteriosus of fetal lambs were studied. Tension of isometric contraction was measured by force displacement transducers. After contraction with oxygen, a control group was compared with rings in which the stimulus for relaxation was either nitrogen gas, prostaglandin E1 (PGE1), nitroglycerin (NTG), or nitroprusside (NPS). During relaxation, tissue was frozen at 30 seconds and at 1, 2, and 5 minutes and analyzed for cAMP and cGMP. PGE1 (10(-6) mol/L) decreased tension by 33% compared with 70% for nitrogen gas, 81% for NTG (10(-5) mol/L), and 92% for NPS (10(-5) mol/L). The maximal relaxation induced by PGE1 was associated with an 11-fold increase in cAMP; PGE1 had no significant effect on cGMP tissue levels. Nitrogen gas, NTG, and NPS produced similar increases in cAMP, and eight-, 25-, and nine-fold increases in cGMP, respectively. These results suggest that the patency of the ductus arteriosus is dependent on activation of both guanylate cyclase and adenylate cyclase and that the nitrovasodilators may be clinically useful in maintaining patency of the ductus arteriosus.
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology*; D006152:Cyclic GMP / Q000494:pharmacology*; D004373:Ductus Arteriosus / Q000187:drug effects* / Q000502:physiology; D005333:Fetus; D007537:Isometric Contraction; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009584:Nitrogen / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D012756:Sheep
D009599:Nitroprusside; D000242:Cyclic AMP; D000527:Alprostadil; D005996:Nitroglycerin; D006152:Cyclic GMP; D009584:Nitrogen