Abstract
The mechanical responses of circular segments of uterine arteries to different combinations of vasoactive agents and putative inhibitors of calcium fluxes were examined using a sensitive in vitro method. Exposure to high potassium (127 mM) or to noradrenaline (NA; 0.1 mM) resulted in a rapid, initial increase in tension of the vascular preparation to reach a sustained level of contraction (approximatively 12 mN) which lasted for at least 15 min. The protein kinase C activator, 4-β-phorbol-12,13-esther-dibutyrate (10 μM), induced a slowly developing but sustained contractile response with maximum (PDBu max) of only 4 mN. Addition of the calcium ionophore, A23187, to PDBu-contracted vessels did not increase tension, while the maximum tension evoked by A23187 per se (3 μM) was 5 mN. Ionomycin had only a small contractile effect on the uterine atery. The contraction evoked by depolarization (potassium) or α 1-adrenoceptor stimulation (NA) was decreased in nominally calcium-free medium containing EDTA (0–100 μM) or EGTA, while uterine arteries loaded intracellularly with the calcium chelator, quin-2, responded to the vasoconstrictors almost as well as the control preparations. Blockade of calcium influx with Cd 2+ (> .01 mM), nifedipine (> 3 μM), verapamil (> 1 μM) and TMB-8 (> 10 μM) reduced the tension evoked by potassium somewhat more than it reduced the contractions induced by NA, while the opposite was seen in the presence of Ni 2+ (> 0.1 mM). Inhibition of calmodulin-dependent enzymes by W7 (> 10 μM) reduced the maximum on evoked by potassium and NA to a similar extent. These data suggest that the strong contractions of uterine arteries primarily depend on calcium mobilized from the extracellular medium through different types of calcium channels, and that activation of a protein kinase C contributes, by approximatively 30% to the contraction.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call