Pharmacological dissection of vascular effects caused by activation of protease-activated receptor 1 and 2 in anesthetized rats

To clarify the role of protease-activated receptor 1 and 2 (PAR-1 and PAR-2) in controlling blood pressure, we evaluated changes in blood pressure induced by a peptide that activates the receptor PAR-1 (PAR-1AP, SFLLRNPND) and a peptide that activates the receptor PAR-2 (PAR-2AP, SLIGRL) in naive and ganglion-blocked anesthetized rats. The role of nitric oxide on the effects observed was also investigated. Intravenous injection of PAR-1AP induced a biphasic change in mean arterial blood pressure (MABP) characterized by hypotension followed by hypertension, the latter was enhanced strongly by ganglion-blockade. After L-NAME infusion in ganglion-blocked rats, hypertension induced by PAR-1AP was still increased, which returned to control value after L-arginine infusion. L-NAME did not inhibit PAR-1AP-induced hypotension. Intravenous injection of PAR-2AP induced a biphasic change in MABP, characterized by hypotension followed by a hypertensive phase that reached the maximum value in 5-6 min. Hypertension was abolished by ganglion-blockade and was restored by an infusion of L-NAME. This effect was reverted by L-arginine. L-NAME reduced the duration of hypotension induced by PAR-2AP. In conclusion, we define that PAR-1 mainly mediates hypertension, whereas PAR-2 mainly is responsible for hypotension. Furthermore, we give evidence for a hypertensive effect of PAR-2AP linked to a reflex mechanism that is modulated by nitric oxide.