Effects of thrombin, PAR-1 activating peptide and a PAR-1 antagonist on umbilical artery resistance in vitro.
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).


CONCLUSIONS
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.
O'Loughlin
Aonghus J
AJ
Dept. of Obstetrics & Gynaecology, National University of Ireland Galway, Clinical Science Institute, University College Hospital Galway, Newcastle Road, Galway, Ireland. aonghus_o_loughlin@hotmail.com <aonghus_o_loughlin@hotmail.com>
O'Sullivan
Crochan J
CJ
Ravikumar
Nandini
N
Friel
Anne M
AM
Elliott
John T
JT
Morrison
John J
JJ
D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009842:Oligopeptides / Q000494:pharmacology*; D011247:Pregnancy; D012701:Serotonin / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology*; D014469:Umbilical Arteries / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors
C510473:N-cinnamoyl-4-fluorophenylalanyl-4-guanidinophenylalanyl-leucyl-arginyl-ornithinamide; D009842:Oligopeptides; C462999:PAR-1-activating peptide; D012701:Serotonin; D013917:Thrombin; D010975:Platelet Aggregation Inhibitors
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