1134 Protease-Activated Receptor (PAR)-Mediated Contraction of the Chicken Ductus Arteriosus

Abstract

Arch Dis Child 2012;97(Suppl 2):A1-A539 A325Abstracts and the PAR2-activating peptide SLIGRL-NH 2 (0.1 to 10 µmol/L) in DA rings from 15-, 19-, and 21-d chicken embryos. Results Thrombin, trypsin, and TFLLR-NH 2 , all caused concentration-dependent contraction of the pulmonary side of chicken DA. These contractions were not observed in the aortic side of the DA, in the femoral artery or in the pulmonary artery. Thrombin-, trypsin-and TFLLR-NH 2 -induced contractions were endotheliumindependent but markedly impaired by the elimination of calcium from the external medium. The contraction evoked by thrombin and trypsin increased between day 15 and 19 of incubation and was not affected by oxygen tension. SLIGRL-NH 2 (≥10 µmol/L), evoked endothelium-dependent relaxation of the DA. Conclusions PARs are functionally present in the chicken DA but not in other vascular tissues. Recent studies demonstrate that loss of platelet number or function leads to defective DA closure. We speculate that the role of platelets in DA closure might be partially mediated through the PAR-mediated vasoactive effects of thrombin.

New Mediators in the Biology of the Ductus Arteriosus: Lessons from the Chicken Embryo

“…Surprisingly, until our study, the possible vascular effects of IsoPs in the DA had not been investigated. We observed that 15-E 2t -IsoP evoked a potent and efficacious, TP receptormediated, contraction in the chicken DA [18]. On the other hand, 15-F 2t -IsoP is probably acting as a partial agonist at TP receptors.…”

“…PAR-1 and PAR-2 have been shown to be involved in regulating vascular tone. Our preliminary results indicate that thrombin, acting through PAR-1, is a selective vasoconstrictor in the DA of the chicken, providing the first functional evidence for a role of PARs in DA biology [18]. Currently, we are analyzing the expression of PARs in the DA of several species (human, lamb, rat, mouse, and chicken).…”