[HTML][HTML] Association of renal injury with nitric oxide deficiency in aged SHR: prevention by hypertension control with AT1 blockade

XJ Zhou, ND Vaziri, J Zhang, HW Wang, XQ Wang - Kidney international, 2002 - Elsevier
XJ Zhou, ND Vaziri, J Zhang, HW Wang, XQ Wang
Kidney international, 2002Elsevier
Association of renal injury with nitric oxide deficiency in aged SHR: Prevention by
hypertension control with AT 1 blockade. Background Aged spontaneously hypertensive rats
(SHR) develop end-stage renal disease resembling that of uncontrolled essential
hypertension in humans. Nitric oxide (NO) and angiotensin II (Ang II) play an important role
in the regulation of blood pressure and the growth of vascular smooth muscle and renal
mesangial cells. The relationship between renal NO system, Ang II activity and renal injury in …
Association of renal injury with nitric oxide deficiency in aged SHR: Prevention by hypertension control with AT1 blockade.
Background
Aged spontaneously hypertensive rats (SHR) develop end-stage renal disease resembling that of uncontrolled essential hypertension in humans. Nitric oxide (NO) and angiotensin II (Ang II) play an important role in the regulation of blood pressure and the growth of vascular smooth muscle and renal mesangial cells. The relationship between renal NO system, Ang II activity and renal injury in aged SHR is not fully understood.
Methods
The 8-week-old SHR were randomized into losartan-treated (30 mg/kg/day for 55 weeks) and vehicle treated groups. The age-matched Wistar-Kyoto rats (WKY) served as controls. Renal histology and tissue expressions of endothelial and inducible NO synthases (eNOS and iNOS) and nitrotyrosine were examined at 63-weeks of age.
Results
Compared to the WKY group, untreated SHR showed severe hypertension, proteinuria, renal insufficiency, a twofold decrease in renal tissue eNOS and iNOS expressions and massive nitrotyrosine accumulation. This was associated with severe glomerulosclerosis, tubular atrophy and interstitial fibrosis. Losartan therapy normalized blood pressure, prevented proteinuria and renal insufficiency, abrogated the fall in renal eNOS and iNOS protein contents, mitigated renal nitrotyrosine accumulation, and prevented the histological abnormalities found in the untreated SHR.
Conclusions
Aged SHR exhibit severe renal lesions with acquired NO deficiency that are prevented by hypertension control with AT1 blockade. These findings point to the possible role of NO deficiency in the pathogenesis of renal lesions in aged SHR.
Elsevier