Proteinase-activated receptor-1 (PAR-1) activation contracts the isolated human renal artery in vitro.

1. The in vitro motor function of protease-activated recepter-1 (PAR-1), PAR-2 and PAR-4 and the presence by immunohistochemistry of PAR-1 in the human renal artery have been investigated. 2. Thrombin and the human PAR-1 (SFLLRN-NH(2)) activating peptide, but not the PAR-1 reverse peptide (NRLLFS-NH(2)), contracted both endothelial-intact and endothelial-denuded human renal artery strips, whereas no relaxation was observed either in strips non-precontracted or precontracted with phenylephrine. Maximum contraction by thrombin or SFLLRN-NH(2) was about 60% of phenylephrine. However, thrombin was approximately 1000-fold more potent than SFLLRN-NH(2). 3. PAR-1 desensitisation, using repeated applications of SFLLRN-NH(2), almost completely blocked the response to thrombin. The contractile effect produced by thrombin and SFLLRN-NH(2) was not affected by nitric oxide synthase inhibition, but was significantly reduced by cyclooxygenase blockade. 4. Trypsin, the PAR-2 (SLIGKV-NH(2) and SLIGRL-NH(2)) and PAR-4 (GYPGQV-NH(2) and AYPGKF-NH(2)) activating peptides did not produce any significant contraction or relaxation. 5. In agreement with the motor function data immunohistochemistry showed specific staining patterns for PAR-1 in the human renal artery. 6. Combined, these studies would suggest a possible role for PAR-1 in renal vascular homeostasis.