title: Barnidipine ameliorates the vascular and renal injury in L-NAME-induced hypertensive rats.
abstract: The present study was aimed to investigate the influence of Barnidipine treatment on early stage hypertension by determining the function and morphology of the mesenteric and renal arteries as well as the kidney in N(ω)-Nitro-L-Arginine Methyl Ester (L-NAME)-induced hypertensive rats. Barnidipine (3 mg/kg/day p.o) was applied to rats after 2 weeks of L-NAME (60 mg/kg/day) administration, and continued for the next 3 weeks concomitantly with L-NAME. The systolic blood pressure (SBP) of rats was determined to decrease significantly in Barnidipine treated hypertensive group when compared to that of rats received L-NAME alone. Myograph studies demonstrated that the contractile reactivity to noradrenaline were significantly reduced in both of the resistance arteries while endothelium-dependent relaxations to acethylcholine were significantly diminished particularly in the mesenteric arteries of L-NAME-induced hypertensive rats. The impaired contractile and endothelial responses were completely restored by concomitant treatment of Barnidipine with L-NAME. Histopathological examinations verified structural alterations in the arteries as well as the kidney. Moreover, a decrease in endothelial nitric oxide synthase (eNOS) expression was presented both in the arteries and kidney of hypertensive rats which were increased following Barnidipine treatment. Elevated plasma levels of malondialdehyde (MDA) and myeloperoxidase (MPO) were also reduced in Barnidipine treated hypertensive rats. In conclusion, besides to its efficacy in reducing the elevated SBP, amelioration of vascular function, modulation of arterial and renal eNOS expressions as well as reduction of the plasma levels of oxidative and inflammatory biomarkers are possible supportive mechanisms mediating the favorable implications of Barnidipine in L-NAME-induced hypertension model.
authors.affiliation: Istanbul University, Faculty of Pharmacy, Department of Pharmacology, 34116 Beyazıt, Istanbul, Turkey. Electronic address: ilkayalp@istanbul.edu.tr.
authors.forename: F Ilkay
authors.initials: FI
authors.lastname: Alp Yildirim
authors.affiliation: Istanbul University, Faculty of Pharmacy, Department of Pharmacology, 34116 Beyazıt, Istanbul, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Eker Kizilay
authors.affiliation: Istanbul University, Faculty of Science, Department of Biology, 34134 Vezneciler, Fatih, Istanbul, Turkey.
authors.forename: Bülent
authors.initials: B
authors.lastname: Ergin
authors.affiliation: Istanbul University, Cerrahpaşa School of Medicine, Department of Biochemistry, 34098 Fatih, Istanbul, Turkey.
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Balci Ekmekçi
authors.affiliation: Istanbul University, Faculty of Pharmacy, Department of Pharmacology, 34116 Beyazıt, Istanbul, Turkey.
authors.forename: Gökçe
authors.initials: G
authors.lastname: Topal
authors.affiliation: Istanbul University, Cerrahpaşa School of Medicine, Department of Biochemistry, 34098 Fatih, Istanbul, Turkey.
authors.forename: Mine
authors.initials: M
authors.lastname: Kucur
authors.affiliation: Istanbul University, Faculty of Science, Department of Biology, 34134 Vezneciler, Fatih, Istanbul, Turkey.
authors.forename: Cihan
authors.initials: C
authors.lastname: Demirci Tansel
authors.affiliation: Istanbul University, Faculty of Pharmacy, Department of Pharmacology, 34116 Beyazıt, Istanbul, Turkey.
authors.forename: B Sönmez
authors.initials: BS
authors.lastname: Uydeş Doğan
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D017208:Rats, Wistar; D012077:Renal Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D066253:Vascular Remodeling / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D018836:Inflammation Mediators; C050699:mepirodipine; D008315:Malondialdehyde; D009195:Peroxidase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D009543:Nifedipine; D019331:NG-Nitroarginine Methyl Ester
keywords: Barnidipine; Kidney; Mesenteric artery; Renal artery; l-NAME-induced hypertension