PAR‐2 RECEPTORS MODULATE NERVE‐EVOKED CONTRACTION OF RESISTANCE ARTERIES

Abstract

The sympathetic nervous system regulates arterial diameter and thus blood flow and blood pressure. Protease‐activated receptors (PARs) are a novel class of G‐protein coupled receptors activated by protealytic cleavage of the extracellular domain to reveal a tethered ligand. Four sub‐types of PARs have been identified, of which PAR‐1 and PAR‐2 are expressed in the vasculature. We have investigated whether activation of PAR‐2 can modulate nerve‐mediated vasoconstriction in rat isolated mesenteric resistance arteries denuded of endothelium. Stimulation of peri‐vascular nerves elicited frequency‐dependent increases in tone which were abolished by the α1‐adrenoceptor antagonist prazosin. Activation of PAR‐2 by either trypsin, the tethered ligand mimetic peptide FLIGRL or AC264613, a synthetic PAR‐2 ligand, significantly attenuated nerve‐mediated responses. Increases in tone to bath applied noradrenaline were attenuated but to a significantly lesser extent. The actions of trypsin were prevented by the trypsin inhibitor aprotinin. Thrombin, which activates PAR‐1 receptors, did not attenuate nerve‐mediated or noradrenaline‐evoked increases in tone. These data indicate that PAR‐2 receptors can modulate nerve‐mediated vasoconstriction of resistance arteries and so may be novel regulators of sympathetic vascular tone.