Chronic nicotine treatment enhances vascular smooth muscle relaxation in rats

Aim: To investigate the effect of chronic nicotine treatment on vascular function and to identify the underlying mechanisms. Methods: Adult rats were treated with nicotine (3 mg.kg(-1).d(-1), sc) for 6 weeks. After the rats were sacrificed, aortic rings were prepared for detecting vascular reactivity, and thoracic aorta and periaortic fat samples were collected for histological and molecular biology studies. Results: Chronic nicotine treatment significantly reduced periaortic fat, and specifically enhanced smooth muscle relaxation without altering the aortic adventitial fat and endothelium function. Pretreatment with the soluble guanylyl cyclase inhibitor ODQ (3 mu mol/L) or PKG inhibitor Rp-8-Br-PET-cGMP (30 mu mol/L) abolished the nicotine-induced enhancement of smooth muscle relaxation, whereas the cGMP analogue 8-Br-cGMP could mimic the nicotine-induced enhancement of smooth muscle relaxation. However, the chronic nicotine treatment did not alter PKG protein expression and activity in aortic media. Conclusion: Chronic nicotine treatment enhances vascular smooth muscle relaxation of rats via activation of PKG pathway.