Resistance to renal damage by chronic nitric oxide synthase inhibition in the Wistar-Furth rat

Authors:
  • APAaron J. Polichnowski
    Aaron J. Polichnowski
  • HLHector Licea-Vargas
    Hector Licea-Vargas
  • MPMaria Picken
    Maria Picken
  • JLJianrui Long
    Jianrui Long
  • RBRashmi Bisla
    Rashmi Bisla
  • GWGeoffrey A. Williamson
    Geoffrey A. Williamson
  • ABAnil K. Bidani
    Anil K. Bidani
  • KGKaren A. Griffin
    Karen A. Griffin
  • LBL. G. Bongartz
    L. G. Bongartz
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Abstract
Chronic nitric oxide synthase inhibition (NOSI) causes chronic kidney disease (CKD) in the Sprague Dawley (SD) rat. We previously showed that the Wistar-Furth (WF) rats are resistant to several models of CKD and maintain renal nitric oxide (NO) production compared with SD rats, whereas low-dose NOSI caused progression of CKD in WF rats. Here, we evaluate the impact of high-dose chronic NOSI in WF and SD rats, as well as intrarenal responses to an acute pressor dose of NOSI in the normal WF. Rats were given NG-nitro-l-arginine methyl ester (l-NAME) (150 and 300 mg/l for 6–10 wk) in the drinking water after an initial bolus tail vein injection. Both strains showed significant reductions in total NO production with chronic l-NAME. SD given 150 mg/l l-NAME for 6 wk developed proteinuria and renal injury, whereas WF rats receiving 150 mg/l l-NAME for 6–10 wk or 300 mg/l for 6 wk developed no proteinuria and minimal renal injury. Blood pressure was significantly elevated with chronic NOSI in both strains but was higher in the SD rat. There was little impact on renal nitric oxide synthase expression with l-NAME, except that cortical endothelial nitric oxide synthase abundance increased in WF after 6 wk (150 mg/l). Micropuncture experiments with acute pressor NOSI resulted in similar increases in systemic blood pressure in SD and WF rats, whereas WF rats showed a much smaller increment in glomerular blood pressure compared with SD rats. In conclusion, WF rats do not develop renal injury after chronic NOSI at, or above, a dose that causes significant injury in the SD rat. This protection may be associated with protection from glomerular hypertension.

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