alpha-Toxin-permeabilised rabbit fetal ductus arteriosus is more sensitive to Ca2+ than aorta or main pulmonary artery

Objectives: 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 E(2) (PGE(2)), 3-isobutyl-1-methylxanthine (IBMX, a phosphodiesterase inhibitor), cyclic adenosine 3',5'-monophosphate (CAMP) and forskolin (an activator of adenylate cyclase) on Ca2+-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 PGE(2), cAMP, IBMX and forskolin was examined on submaximal Ca2+-activated force (0.3 mu M Ca2+) in preparations from rabbit ductus arteriosus. 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) and 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+-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 PGE(2) levels fall after birth.