Role of nitric oxide deficiency in the development of hypertension in hydronephrotic animals

Mattias Carlstrom, Russell Deputy Brown, Jenny Edlund, Johan Sallstrom, Erik Larsson, Tom Teerlink, Frederick Palm, Nils Wahlin, Erik Persson

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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 L-NAME or L-arginine. Blood samples for ADMA, SDMA, L-arginine analysis were taken and the renal tissue was used for histology and determination of NOS proteins. TGF-characteristics were determined by stop-flow pressure technique before and after administration of 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, 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 eNOS proteins were lower in animals with hydronephrosis. In conclusion, 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.
Original languageEnglish
Pages (from-to)1 - 37
Number of pages37
JournalAmerican Journal of Physiology-Renal Physiology
Publication statusPublished - 2008

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