Pharmacological characterization of cellular mechanisms of the renal vasodilatory effect of nicotine in rats

详细信息    查看全文

• 作者：Mahmoud M. El-Mas ; Sahar M. El-gowilly ; Eman Y. Gohar ; Abdel-Rheem M. Ghazal
• 关键词：Nicotine ; Endothelium ; Nitrergic neurotransmission ; Perfused kidney ; Vasodilation ; Nitric oxide synthase ; K⁺ channels
• 刊名：European Journal of Pharmacology
• 出版年：2008
• 出版时间：7 July 2008
• 年：2008
• 卷：588
• 期：2-3
• 页码：294-300
• 全文大小：374 K

文摘

Nicotine causes vasodilation in the renal vasculature through as yet unidentified mechanism. This study investigated the role of endothelial and non-endothelial factors in the vasodilatory action of nicotine in the rat isolated kidney. Nicotine vasodilation in phenylephrine-preconstricted perfused kidneys was evaluated in the absence and presence of drugs that interfere with nitric oxide synthase (NOS), K⁺ channels, cholinergic or adrenergic activity. Nicotine infusion (5 × 10^{"12; 5}, 1 × 10^{"12; 4}, and 5 × 10^{"12; 4} M) produced concentration-dependent decreases in the renal perfusion pressure, which continued for 20 min with a peak depressor effect observed at approximately 3 min. Nicotine vasodilation was associated with increases in norepinephrine and NO metabolites (nitrite/nitrate, NOx) levels in the renal effluent. Chemical denudation of the endothelium with 3-[(3-cholamidopropyl)-dimethyl-ammonio]-1-propane-sulfonate (CHAPS), or inhibition of NOS (N^G-nitro-L-arginine, L-NNA), or guanylate cyclase (methylene blue) almost abolished the renal vasodilatory action of nicotine. Nicotine vasodilation was also significantly attenuated after selective blockade of ATP-sensitive (K_ATP, glibenclamide) or inward rectifier (K_ir, BaCl₂) K⁺ channels but remained unaltered after blockade of large-conductance calcium-activated (BK_Ca, tetraethylammonium, TEA) or voltage-dependent (K_v, 4-aminopyridine) K⁺ channels. Hexamethonium (ganglionic blocker), propranolol (β-adrenceptor blocker), guanethidine (adrenergic neuron blocker), atropine (muscarinic antagonist) or the use of kidneys preconstricted with 80 mM KCl reduced the vasodepressor action of nicotine. Finally, exposure to diclophenac or neostigmine had no effect on nicotine vasodilation. Together, these findings implicate endothelial NOS and K_ATP and K_ir channels in the renal vasodepressor effect of nicotine. Further, the sympathetic-dependent NO-mediated neurogenic vasodilation apparently contributes, at least partly, to nicotine vasodilation.