Lipid soluble smoke particles upregulate endothelin receptors in rat basilar artery

The present study examines the effect of dimethylsulphoxide-soluble particles (DSP) from cigarette smoke on endothelin (ET) receptors in the basilar artery. The contractile responses to ET-1 (ETA and ETB receptors agonist) and sarafotoxin 6c (ETB receptor agonist) were studied using a sensitive myograph. The mRNA levels of ET receptors were determined with real-time PCR, while the protein level was evaluated by immunohistochemistry. The results showed that a DSP concentration of 0.4 μl/ml increased the contractile responses induced by sarafotoxin 6c and ET-1 and the mRNA and protein levels of the ET receptors. Inhibitor SB203580 (a p38 inhibitor), staurosporine (a PKC inhibitor) or wedelolactone (a NF-κB inhibitor) attenuated the elevated sarafotoxin 6c-induced contraction, the increased mRNA expression and protein levels of the ETB receptor induced by DSP. The effects on the ETA receptor induced by DSP 0.4 μl/ml were inhibited by co-incubation with PD98059 (an ERK1/2 inhibitor) or SP600125 (a JNK inhibitor) and were further enhanced by SB203580. The results indicate that DSP 0.4 μl/ml upregulates the ETB receptor of basilar arterial smooth muscle cells via activation of the p38 pathway and transcriptional factor NF-κB, while also upregulating the ETA receptor via activation of the ERK1/2 and JNK pathways. Additionally, the p38 pathway seems to be involved in the feedback regulation of the ETA receptor.