Pharmacological characterization of cellular mechanisms of the renal vasodilatory effect of nicotine in rats.
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 x 10(-5), 1 x 10(-4), and 5 x 10(-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 (NG-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 (Kir, BaCl2) K+ channels but remained unaltered after blockade of large-conductance calcium-activated (BKCa, tetraethylammonium, TEA) or voltage-dependent (Kv, 4-aminopyridine) K+ channels. Hexamethonium (ganglionic blocker), propranolol (beta-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 KATP and Kir channels in the renal vasodepressor effect of nicotine. Further, the sympathetic-dependent NO-mediated neurogenic vasodilation apparently contributes, at least partly, to nicotine vasodilation.
El-Mas
Mahmoud M
MM
Department of Pharmacology, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt. mahelm@hotmail.com <mahelm@hotmail.com>
El-Gowilly
Sahar M
SM
Gohar
Eman Y
EY
Ghazal
Abdel-Rheem M
AR
D000818:Animals; D002793:Cholic Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply*; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000502:physiology; D010477:Perfusion; D015221:Potassium Channels / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*
D002793:Cholic Acids; D015221:Potassium Channels; D011453:Prostaglandins; D009569:Nitric Oxide; D009538:Nicotine; D019001:Nitric Oxide Synthase; C028213:3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate