Wm. Cheung et al., RECEPTOR-ACTIVATING PEPTIDES DISTINGUISH THROMBIN RECEPTOR (PAR-1) AND PROTEASE ACTIVATED RECEPTOR-2 (PAR-2) MEDIATED HEMODYNAMIC-RESPONSESIN-VIVO, Canadian journal of physiology and pharmacology, 76(1), 1998, pp. 16-25
Vascular expression and cellular functions of the thrombin receptor (P
AR-1) and protease activated receptor 2 (PAR-2) suggest similar but di
stinct vascular regulatory roles. The vascular actions of PAR-I and PA
R-2 in vivo were differentiated by monitoring mean arterial pressure (
MAP) and heart rate (HR) of anesthetized mice in response to intraveno
us SFLLRN (0.1, 0.3, and 1 mu mol/kg) and SLIGRL (0.1, 0.3, and 1 mu m
ol/kg), the respective receptor-activating sequences for PAR-1 and PAR
-2, and TFLLRNPNDK (0.3, 1, and 3 mu mol/kg), a synthetic peptide sele
ctive for PAR-1. All peptides dose dependently decreased MAP (order of
potency: SLIGRL > SFLLRN > TFLLRNPNDK). SLIGRL induced a more prolong
ed hypotension with a slow return to baseline, whereas SFLLRN- and TFL
LRNPNDK-induced hypotension was followed by a rapid return towards bas
eline and a sustained moderate hypotension SFLLRN and TFLLRNPNDK, but
not SLIGRL, decreased HR. N-omega-Nitro-L-arginine methyl ester HCl (L
-NAME), an inhibitor of nitric oxide synthesis, attenuated the cumulat
ive hypotensive response to SLIGRL but had no effect on the SFLLRN and
TFLLRNPNDK hypotension. However, L-NAME revealed a rebound hypertensi
on in response to SFLLRN and TFLLRNPNDK but not SLIGRL. In conclusion,
activation of either PAR-I or PAR-2 in vivo results In hypotension. I
n addition, only PAR-1 activation induced hypertension following L-NAM
E, reflecting concurrent PAR-1-mediated vasoconstriction. Thus, these
different hemodynamic responses in vivo suggest distinct physiological
or pathophysiological roles for PAR-I and PAR-2 in local vascular reg
ulation.