Calcium influx and protein kinase C activation involved in uterine vasoconstriction in guinea pigs.
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-beta-phorbol-12,13-esther-dibutyrate (10 microM), induced a slowly developing but sustained contractile response with a maximum (PDBumax) 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 microM) was 5 mN. Ionomycin had only a small contractile effect on the uterine artery. The contraction evoked by depolarization (potassium) or alpha 1-adrenoceptor stimulation (NA) was decreased in nominally calcium-free medium containing EDTA (0-100 microM) 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 Cd2+ (greater than 0.01 mM), nifedipine (greater than 3 microM), verapamil (greater than 1 microM) and TMB-8 (greater than 10 microM) 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 Ni2+ (greater than 0.1 mM). Inhibition of calmodulin-dependent enzymes by W7 (greater than 10 microM) reduced the maximum tension evoked by potassium and NA to a similar extent.(ABSTRACT TRUNCATED AT 250 WORDS)
Fallgren
B
B
Department of Zoophysiology, University of Lund, Sweden.
Bergstrand
H
H
Edvinsson
L
L
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects; D014599:Uterus / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D011493:Protein Kinase C; D002118:Calcium; D009638:Norepinephrine