Relaxant and contractile responses of porcine pulmonary arteries to thrombin and thrombin receptor activating peptides.

Abstract

The vascular effects of thrombin and thrombin receptor activating peptides (TRAP) were studied on isolated rings from porcine pulmonary arteries. In prostaglandin F2 alpha (PGF2 alpha)-precontracted vessels with intact endothelium, both thrombin- and TRAP-induced nitric oxide-mediated relaxation, whereas in endothelium-denuded vessels thrombin and TRAP elicited concentration-dependent contractile responses. The first phasic component of contraction was associated with increased generation of inositol 1,4,5-triphosphate and the tonic component seemed to be due to the activation of protein kinase C. Both peptides (TRAP-6 with 6 and TRAP-14 with 14 amino acid residues) did not differ in their intrinsic activity; like thrombin, both peptides elicited dualistic vascular effects but their potency was more than three orders of magnitude less than that of thrombin.