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Cardiovascular Research 1997 33(1):223-229; doi:10.1016/S0008-6363(96)00171-X
© 1997 by European Society of Cardiology
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Copyright © 1997, European Society of Cardiology

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

Catherine A. Crichtona,*, Gordon C.S. Smithb and Godfrey L. Smitha

aInstitute of Biological and Life Sciences, West Medical Building, Glasgow University, Glasgow, G12 8QQ, UK
bDept of Obstetrics and Gynaecology, Glasgow Royal Infirmary, Glasgow, UK

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 E2 (PGE2), 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 PGE2, cAMP, IBMX and forskolin was examined on submaximal Ca2+-activated force (0.3 µM 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 µM) than its two neighbouring blood vessels aorta (EC50, 0.52 µM) and main pulmonary artery (EC50, 0.72 µM). Submaximal Ca2+-activated force (0.3 µM Ca2+) was depressed by PGE2 (1 nM) in the presence of IBMX (10 µM), by cAMP (10 and 100 µM) and by forskolin alone (0.1 µM and 1 µM). Conclusion: PGE2-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 PGE2 levels fall after birth.

KEYWORDS {alpha}-Toxin; Calcium sensitivity – Ductus arteriosus – Prostaglandin – cAMP – Rabbit, vascular myocytes – Rabbit arteries


* Corresponding author. Tel. +44 141 330-5963; Fax +44 141 330-4612.


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