Increased vascular contractility in isolated vessels from cigarette smoking rats is mediated by basal endothelin release

The effect of chronic cigarette smoking on endothelin modulation of vascular contraction and CYP enzyme levels was studied in 20 male Sprague-Dawley rats. The animals were divided equally into smoking and non-smoking groups. The smoking group was exposed to 6 research cigarettes per rat per day 5 days a week for 16 weeks. The control group was sham smoked. Functional contractile studies were performed in aortas and carotid arteries to determine the regulation of vascular tone by basal release of endothelin. Liver samples were analyzed for CYPIAI and CYPIA2 gene expression by RT-PCR. Plasma samples were assessed for endothelin-l (ET-l) level by enzyme immunoassay (EIA). Treatment of aortas and carotid arteries with bosentan, the dual endothelin receptor antagonist, caused a significant reduction in constrictor responses of smoking rats, indicating increased regulation of tone by endothelin in smoker rats as compared to controls. There was also a greater expression of the cytochrome P450-liver enzymes (CYPIAI and CYPIA2) in smoker rats. Body weight gain was also significantly decreased in smoker rats. We conclude that increased endothelin release in smoker rats contributes significantly to increased arterial tone and may therefore contribute to the cardiovascular pathophysiology associated with cigarette smoking, such as increased vascular muscularization, increased contraction, decreased dilation and possibly vasospasm.Medicine, Faculty ofAnesthesiology, Pharmacology and Therapeutics, Department ofGraduat