ALPHA-TOXIN-PERMEABILIZED RABBIT FETAL DUCTUS-ARTERIOSUS IS MORE SENSITIVE TO CA2-ARTERY( THAN AORTA OR MAIN PULMONARY)

Objectives: The Ca2+ sensitivity of contractile protein-generated tens ion production was measured in the smooth muscle of the rabbit ductus arteriosus and compared with two neighbouring fetal blood vessels (mai n pulmonary artery and aorta). The effect of prostaglandin E(2) (PGE(2 )), 3-isobutyl-1-methylxanthine (IBMX, a phosphodiesterase inhibitor), cyclic adenosine 3',5'-monophosphate (CAMP) and forskolin (an activat or of adenylate cyclase) on Ca2+-activated force generated by preparat ions from ductus arteriosus was also examined, Methods: Strips of smoo th 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 PGE(2), cAMP, IBMX and forskolin was examined on submaximal Ca2+-a ctivated force (0.3 mu M Ca2+) in preparations from rabbit ductus arte riosus. Results: Permeabilised smooth muscle from fetal rabbit ductus arteriosus was significantly more sensitive to Ca2+ (EC(50), 0.20 mu M ) than its two neighbouring blood Vessels aorta (EC(50), 0.52 mu M) an d main pulmonary artery (EC(50), 0.72 mu M). Submaximal Ca2+-activated force (0.3 mu M Ca2+) was depressed by PGE(2) (1 nM) in the presence of IBMX (10 mu M), by cAMP (10 and 100 mu M) and by forskolin alone (0 .1 mu M and 1 mu M). Conclusion: PGE(2)-mediated depression of Ca2+-ac tivated force in the smooth muscle of the ductus arteriosus may play a role in the maintenance of a patent ductus arteriosus in the fetus. T he intrinsically high Ca2+ sensitivity of smooth muscle contractile pr oteins may aid the sustained vasoconstriction of the ductus when the P GE(2) levels fall after birth.