Aim This study sought to investigate the effect of chronic nicotine exposure on vascular function and to identify the underlying mechanisms. Methods Isolated organ bath studies were performed to examine the effects of...Aim This study sought to investigate the effect of chronic nicotine exposure on vascular function and to identify the underlying mechanisms. Methods Isolated organ bath studies were performed to examine the effects of chronic nicotine exposure on vascular reactivity of the aorta in Sprague-Dawley rats. We used various analogues and blockers of the cGMP-dependent protein kinase （PKG） pathway as well as molecular techniques to identify the un- derlying mechanisms. Results Chronic nicotine exposure reduced periaortic fat and specifically enhanced smooth muscle relaxation, although aortic adventitial fat and endothelium function were not affected. The soluble guanylyl cyclase inhibitor ODQ or PKG inhibitor Rp-8-Br-PET-cGMP abolished the difference in relaxation between the sa- line and nicotine group, and the cGMP analogue 8-Br-cGMP mimicked the difference in relaxation. PKG protein expression and activity were not altered after nicotine treatment. Conclusion Chronic nicotine exposure enhances vascular smooth muscle relaxation through a cGMP-dependent PKG pathway. Our findings provide novel insights in- to nicotine pharmacology.展开更多
文摘Aim This study sought to investigate the effect of chronic nicotine exposure on vascular function and to identify the underlying mechanisms. Methods Isolated organ bath studies were performed to examine the effects of chronic nicotine exposure on vascular reactivity of the aorta in Sprague-Dawley rats. We used various analogues and blockers of the cGMP-dependent protein kinase （PKG） pathway as well as molecular techniques to identify the un- derlying mechanisms. Results Chronic nicotine exposure reduced periaortic fat and specifically enhanced smooth muscle relaxation, although aortic adventitial fat and endothelium function were not affected. The soluble guanylyl cyclase inhibitor ODQ or PKG inhibitor Rp-8-Br-PET-cGMP abolished the difference in relaxation between the sa- line and nicotine group, and the cGMP analogue 8-Br-cGMP mimicked the difference in relaxation. PKG protein expression and activity were not altered after nicotine treatment. Conclusion Chronic nicotine exposure enhances vascular smooth muscle relaxation through a cGMP-dependent PKG pathway. Our findings provide novel insights in- to nicotine pharmacology.
