title: Comparable renovascular protective effects of moxonidine and simvastatin in rats exposed to cigarette smoke.
abstract: Renovascular impairment plays a major role in smoking-induced nephrotoxicity. This study investigated the effect of the imidazoline I(1)-receptor/alpha(2)-adrenoceptor agonist moxonidine, as compared to the lipid lowering drug simvastatin, on abnormalities induced by cigarette smoke (CS) in renovascular reactivity. Six rat groups were used: control, CS (twice a day for 6weeks), simvastatin, moxonidine, CS+simvastatin, and CS+moxonidine. CS exposure increased plasma urea and creatinine and reduced plasma and renal nitrate/nitrite (NOx). In isolated perfused phenylephrine-preconstricted kidneys of CS rats, vasodilator responses to carbachol or isoprenaline, but not papaverine, were attenuated. Nitric oxide synthase (NOS) inhibition by N(G)-nitro-L-arginine (L-NNA) reduced carbachol vasodilations in control but not CS kidneys, suggesting the impairment of NOS activity by CS. Simultaneous administration of moxonidine or simvastatin abolished CS-induced abnormalities in indices of renal function, NOx, and vasodilations caused by carbachol or isoprenaline. The possibility whether alterations in antioxidant or lipid profiles contributed to the interaction was investigated. CS increased renal malondialdyde and decreased glutathione, and glutathione peroxidase, superoxide dismutase and catalase activities. Further, CS reduced plasma HDL and increased cholesterol, triglycerides, and LDL. Simvastatin or moxonidine abolished the deleterious CS effects on antioxidant activity; the lipid profile was normalized by simvastatin only. These findings highlight that renovascular dysfunction caused by CS and the underlying oxidative damage is evenly attenuated by moxonidine and simvastatin.
authors.affiliation: Department of Pharmacology, Medical Research Institute, Faculty of Pharmacy, University of Alexandria, Egypt.
authors.forename: Magda A
authors.initials: MA
authors.lastname: Nasr
authors.forename: Sahar M
authors.initials: SM
authors.lastname: El-Gowilly
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: El-Mas
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D007677:Kidney Function Tests; D008055:Lipids / Q000097:blood; D008297:Male; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D000960:Hypolipidemic Agents; D007093:Imidazoles; D008055:Lipids; D014028:Tobacco Smoke Pollution; D019821:Simvastatin; C043482:moxonidine; D019001:Nitric Oxide Synthase