title: Role of nitric oxide deficiency in the development of hypertension in hydronephrotic animals.
abstract: Hydronephrotic animals develop renal injury and hypertension, which is associated with an abnormal tubuloglomerular feedback (TGF). The TGF sensitivity is coupled to nitric oxide (NO) in the macula densa. The involvement of reduced NO availability in the development of hypertension in hydronephrosis was investigated. Hydronephrosis was induced by ureteral obstruction in young rats. Blood pressure and renal excretion were measured in adulthood, under different sodium conditions, and before and after chronic administration of either N(G)-nitro-l-arginine methyl ester (l-NAME) or l-arginine. Blood samples for ADMA, SDMA, and l-arginine analysis were taken and the renal tissue was used for histology and determination of NO synthase (NOS) proteins. TGF characteristics were determined by stop-flow pressure technique before and after administration of 7-nitroindazole (7-NI) or l-arginine. Hydronephrotic animals developed salt-sensitive hypertension, which was associated with pressure natriuresis and diuresis. The blood pressure response to l-NAME was attenuated and l-arginine supplementation decreased blood pressure in hydronephrotic animals, but not in the controls. Under control conditions, reactivity and sensitivity of the TGF response were greater in the hydronephrotic group. 7-NI administration increased TGF reactivity and sensitivity in control animals, whereas, in hydronephrotic animals, neuronal NOS (nNOS) inhibition had no effect. l-Arginine attenuated TGF response more in hydronephrotic kidneys than in controls. The hydronephrotic animals displayed various degrees of histopathological changes. ADMA and SDMA levels were higher and the renal expressions of nNOS and endothelial NOS proteins were lower in animals with hydronephrosis. Reduced NO availability in the diseased kidney in hydronephrosis, and subsequent resetting of the TGF mechanism, plays an important role in the development of hypertension.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. Mattias.Carlstrom@mcb.uu.se
authors.forename: Mattias
authors.initials: M
authors.lastname: Carlström
authors.forename: Russell D
authors.initials: RD
authors.lastname: Brown
authors.forename: Jenny
authors.initials: J
authors.lastname: Edlund
authors.forename: Johan
authors.initials: J
authors.lastname: Sällström
authors.forename: Erik
authors.initials: E
authors.lastname: Larsson
authors.forename: Tom
authors.initials: T
authors.lastname: Teerlink
authors.forename: Fredrik
authors.initials: F
authors.lastname: Palm
authors.forename: Nils
authors.initials: N
authors.lastname: Wåhlin
authors.forename: A Erik G
authors.initials: AE
authors.lastname: Persson
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004231:Diuresis / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006869:Hydronephrosis / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006973:Hypertension / Q000209:etiology / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000172:deficiency*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D011188:Potassium / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D014517:Ureteral Obstruction / Q000150:complications
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D017673:Sodium Chloride, Dietary; D009569:Nitric Oxide; C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine; D012964:Sodium; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D011188:Potassium; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester