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O'Loughlin, AJ;O'Sullivan, CJ;Ravikumar, N;Friel, AM;Elliott, JT;Morrison, JJ
Reproductive Biology And Endocrinology
Effects of thrombin, PAR-1 activating peptide and a PAR-1 antagonist on umbilical artery resistance in vitro
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Background: The non-thrombotic effects of thrombin in cardiovascular tissues, as mediated via the protease activated receptors (PARs), and particularly PAR-1, have been the focus of much recent research. The aims of this study were to evaluate the effects of thrombin, a specific PAR-1 activating peptide (PAR1-AP), and a PAR-1 antagonist on human umbilical artery tone in vitro.Methods: Human umbilical artery samples were obtained from 17 women at term. Arterial rings were suspended under physiologic conditions for isometric recording. The in vitro effects of thrombin (0.5 units/mL to 3 units/mL), PAR1-AP TFLLR-NH2 [10(-9) to 10(-6) M], and PAR-1 antagonist (N-trans cinnamoyl-p-fluoroPhe- p-guanidinoPhe-Leu-Arg-Orn-NH2) [10(-9) M to 10(5) M] on umbilical artery tone were measured.Results: Both thrombin and TFLLR-NH2 exerted a potent cumulative vasodilatory effect on human umbilical artery resistance (P < 0.001). The mean net maximal inhibition (MMI) for thrombin was 53.05% (n = 6; SEM = 1.43) at tissue bath concentration of 3 units/mL. The MMI with TFLLR-NH2 was 61.50% (n = 6; SEM = 1.43) at bath concentration of 10(-6) M. In comparison to vehicle control, the PAR-1 antagonist did not show a significant relaxant or contractile effect (P > 0.05).Conclusion: These findings highlight a potential role for thrombin and PAR-1 receptors in vascular regulation of feto-placental blood flow in normal pregnancy, and in association with the vascular lesions associated with IUGR and pre-eclampsia.
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