VASCULAR EFFECTS OF PROTEINASE-ACTIVATED-RECEPTOR-2 AGONIST PEPTIDE

Proteinase-activated receptor 2 (PAR-2) is a G protein-coupled recepto r related to the thrombin receptor. PAR-2 can be activated by trypsin and by synthetic peptides corresponding to the new amino terminus gene rated by activating proteolytic cleavage. We show in this report that intravenous injection of PAR-2 agonist peptides has dramatic effects o n arterial blood pressure in anesthetized rats. The peptide SLIGRLETQP PI, at 150 nmol/kg, transiently decreased the mean arterial pressure f rom 104 to 60 mm Hg. The hypotensive response was dose-dependent, and was not secondary to effects on central vasoregulatory systems, heart rate, or the kidneys. A nitric oxide synthase inhibitor attenuated the hypotensive response induced by the PAR-2 agonist peptide. Further ex periments in vitro, on preparations of rat femoral artery and vein, sh owed that PAR-2 agonist peptide elicited a dose-dependent relaxation o f both types of vessel. Removal of the endothelium abolished the agoni st peptide-induced relaxation. Our results demonstrate that activation of PAR-2 can modulate vascular tone, and that this response was an ef fect mediated at least partly by nitric oxide. The effect on blood ves sels further suggests that the physiological activator of this proteol ytically activated receptor is an enzyme present and active in the blo od, possibly after a vascular injury.