title: alpha-Toxin-permeabilised rabbit fetal ductus arteriosus is more sensitive to Ca2+ than aorta or main pulmonary artery.
abstract: OBJECTIVE
  The Ca2+ sensitivity of contractile protein-generated tension production was measured in the smooth muscle of the rabbit ductus arteriosus and compared with two neighbouring fetal blood vessels (main pulmonary artery and aorta). The effect of prostaglandin E2 (PGE2), 3-isobutyl-1-methylxanthine (IBMX, a phosphodiesterase inhibitor), cyclic adenosine 3'5'-monophosphate (CAMP) and forskolin (an activator of adenylate cyclase) on Ca(2+)-activated force generated by preparations from ductus arteriosus was also examined.
  
  
  METHODS
  Strips of smooth muscle from the three vessels were permeabilised using crude alpha-toxin from Staphylococcus aureus. The relationship between [Ca2+] and force production was then measured in the three tissues and the effect of PGE2, cAMP, IBMX and forskolin was examined on submaximal Ca(2+)-activated force (0.3 microM Ca2+) in preparations from rabbit ductus arteriosus.
  
  
  RESULTS
  Permeabilised smooth muscle from fetal rabbit ductus arteriosus was significantly more sensitive to Ca2+ (EC50, 0.20 microM) than its two neighbouring blood vessels aorta (EC50, 0.52 microM) and main pulmonary artery (EC50, 0.72 microM). Submaximal Ca(2+)-activated force (0.3 microM Ca2+) was depressed by PGE2 (1 nM) in the presence of IBMX (10 microM), by cAMP (10 and 100 microM) and by forskolin alone (0.1 microM and 1 microM).
  
  
  CONCLUSIONS
  PGE2-mediated depression of Ca(2+)-activated force in the smooth muscle of the ductus arteriosus may play a role in the maintenance of a patent ductus arteriosus in the fetus. The intrinsically high Ca2+ sensitivity of smooth muscle contractile proteins may aid the sustained vasoconstriction of the ductus when the PGE2 levels fall after birth.
authors.affiliation: Institute of Biological and Life Sciences, Glasgow University, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Crichton
authors.forename: G C
authors.initials: GC
authors.lastname: Smith
authors.forename: G L
authors.initials: GL
authors.lastname: Smith
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000096:biosynthesis; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000196:embryology; D002118:Calcium / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D003864:Depression, Chemical; D015232:Dinoprostone / Q000494:pharmacology; D004373:Ductus Arteriosus / Q000187:drug effects* / Q000196:embryology; D004789:Enzyme Activation; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010477:Perfusion; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000196:embryology; D011817:Rabbits; D010738:Type C Phospholipases / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D010726:Phosphodiesterase Inhibitors; D005576:Colforsin; D000242:Cyclic AMP; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; D015232:Dinoprostone; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine