Beschreibung:
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<jats:bold>
<jats:italic>Objective—</jats:italic>
</jats:bold>
Proteinase-activated receptor-2 is widely expressed in vascular tissue and in highly vascularized organs in humans and other species. Its activation mainly causes endothelium-dependent vasorelaxation in vitro and hypotension in vivo. Here, using nonobese diabetic (NOD) mice at different disease stages, we have evaluated the role of PAR
<jats:sub>2</jats:sub>
in the arterial vascular response during diabetes progression.
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<jats:p>
<jats:bold>
<jats:italic>Methods and Results—</jats:italic>
</jats:bold>
High (NOD-II; 20 to 500 mg/dL) or severe glycosuria (NOD-III; 500 to 1000 mg/dL) provokes a progressive reduction in the response to acetylcholine paralleled by an increase in the vasodilatory response to PAR
<jats:sub>2</jats:sub>
stimulation. Western blot and quantitative real-time polymerase chain reaction (RT-PCR) studies showed that this effect is tied to an increased expression of PAR
<jats:sub>2</jats:sub>
coupled to cyclooxygenase-2 expression. Pharmacological dissection performed with specific inhibitors confirmed the functional involvement of cyclooxygenase-2 in PAR
<jats:sub>2</jats:sub>
vasodilatory effect. This vasodilatory response was confirmed to be dependent on expression of PAR
<jats:sub>2</jats:sub>
in the smooth muscle component by immunohistochemistry studies performed on aorta isolated by both NOD-III and transgenic PAR
<jats:sub>2</jats:sub>
mice.
</jats:p>
<jats:p>
<jats:bold>
<jats:italic>Conclusions—</jats:italic>
</jats:bold>
Our data demonstrate an important role for PAR
<jats:sub>2</jats:sub>
in modulating vascular arterial response in diabetes and suggest that this receptor could represent an useful therapeutic target.
</jats:p>