Objective:

Cigarette smoking is a strong risk factor for stroke. We examined if DMSO-lipid soluble cigarette smoking particles (DSP) enhance the expression of contractile endothelin type B receptors (ETB) and Thromboxane A2 receptors (TP) in rat middle cerebral arteries (MCAs).

Methods:

Kentucky research cigarettes were smoked with vacuum through a filter and the smoke particles retrieved on the filter were dissolved in DMSO. MCAs from adult male Sprague Dawley rats were organ cultured for 24 h in presence of 0.15 ml DSP or DMSO (control). Contractile responses to ETB receptor agonist sarafotoxin (S6c) or the TP receptor agonist U46619 were studied by a myograph. Real time PCR and immunohistochemistry were used to semi-quantify the ETB and TP receptor mRNA and protein expressions.

Results:

DSP enhanced S6c induced contraction of the MCAs and increased the maximal contraction (Emax) from 60 ± 7% (mean ±s.e.m. in % of 60 mM potassium) to 105 ±10% (p<0.05). The Emax of U46619 induced contraction was also significantly increased by DSP, from 112 ±5% to 148 ±12% (p<0.05). Real time PCR and immunohistochemistry showed that DSP upregulated both ETB and TP receptor mRNA and protein expressions in the smooth muscle.

Conclusion:

We have demonstrated for the first time that DSP enhanced the expression of ETB and TP receptors in the MCAs. The enhanced ETB and TP receptor-mediated contraction by DSP might contribute to cigarette smoking-associated stroke.