The actions of mouse mast cell protease-7 and calcium-activated potassium channel inhibitors on PAR2-induced relaxation of the aorta in mice

Abstract

Proteinase-activated receptor 2 (PAR2) may link inflammation with the progression of cardiovascular diseases. We examined the potential of mouse mast cell protease 7 (mMCP-7), an enzyme similar to human mast cell β-tryptase (hMCβ-tryptase), to activate PAR2-dependent vasodilation and the interaction of Ca²⁺-activated K⁺ channel (KCa ) activation by PAR2 with eNOS-dependent relaxation in the aorta. Aortas from mice expressing PAR2 (PAR2 +/+) and PAR2 knockout (PAR2 -/-) mice were used to bioassay the PAR2 activity of mMCP-7 and PAR2-activating peptide (2fly) in the presence of inhihitors of KCa.mMCP-7 did not produce relaxation responses like hMCβ-tryptase in the mouse aorta and inhihitors of KCa channels did not affect PAR2-mediated endothelial nitric oxide synthase dependent-relaxations of the aorta. These data highlight species and mechanistic heterogeneity in the ability of an orthologous enzyme agonist to activate PAR2 in different arteries. The results emphasize the need for cautions interpretations of studies assessing the pathophysiological role of PAR2 in different animal models.