Secondhand cigarette smoke induces increased expression of contractile endothelin receptors in rat coronary arteries via a MEK1/2 sensitive mechanism

Objectives: Cigarette smoke, a strong risk factor for cardiovascular diseases, upregulates contractile endothelin (ET) receptors in coronary arteries. The present study examined the effects of second hand cigarette smoke exposure on the contractile endothelin receptors and the role of the MEK1/2 pathway in rat coronary arteries. Design: Rats were exposed to secondhand smoke (SHS) for 8 weeks followed by intraperitoneal injection of a MEK1/2 inhibitor, U0126 daily for another 4 weeks. Contractile responses of isolated coronary arteries were recorded by a sensitive wire myograph. The receptor protein expression levels were examined by Western blotting. Results: The results showed that SHS in vivo caused increased expression of ET receptors ET_A and ET_B, and that the MEK1/2 blocker U0126 significantly reversed SHS exposure-increased ET_A-mediated contractile responses and protein levels. Similar alterations were observed in ET_B receptors. U0126 showed dose-dependent effects on SHS-induced response on contractile property and protein levels of the ET_B receptor. However, only the higher dose U0126 (15 mg/kg) had inhibitory effects on the ET_A receptor. Conclusions: Taken together, our data show that SHS increases contractile ET receptors and MEK1/2 pathway inhibitor offsets SHS exposure-induced ET_A and ET_B receptor upregulation in rat coronary arteries.