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Recent studies show nitric oxide (NO) deficiency is both a cause and consequence of chronic kidney disease (CKD). Reduced renal neuronal NO synthase (nNOS) abundance and activity parallel development of CKD with different models in the Sprague-Dawley (SD) rats, whereas Wistar Furth (WF) rats are protected against CKD and show preserved renal NO production. In this study, we compared renal NO in response to DOCA/salt-induced injury between the WF and SD. Studies were conducted on sham WF (n = 6) and SD (n = 6) and uninephrectized (UNX)+75 mg DOCA+1% NaCl (WF n = 9; SD n = 10) rats followed for 5 wk. Kidneys were harvested for Western blot, NOS activity, and histology. Other measurements included creatinine clearance and 24-h total NO production and urinary protein excretion. Absolute values of kidney weight were lower in WF than SD rats that showed similar percent increases with UNX+DOCA/NaCl. Proteinuria and decreased creatinine clearance were present in the SD but not the WF rats following UNX+DOCA/NaCl. Glomerular injury was mild in the WF compared with SD rats that showed many globally damaged glomeruli. Although renal nNOS abundance was decreased in both strains (higher baseline in WF), soluble NOS activity was maintained in the WF hut significantly reduced in the SD rats. Renal endothelial NOS abundance and membrane NOS activity were unaffected by treatment. In summary, WF rats showed resistance to UNX+DOCA/NaCl-induced CKD with maintained renal NO production despite mild reduction in nNOS abundance. Further studies are needed to evaluate how WF rats maintain renal NO production despite similar changes in abundance as the vulnerable SD strain. neuronal nitric oxide synthase; endothelial nitric oxide synthase; nitric oxide synthase activity; glomerulosclerosis; creatinine clearance

The Wistar-Furth (WF) rat is protected against chronic renal disease (CRD) following 5/6th ablation/infarction vs. the Sprague-Dawley (SD) rat, and protection was associated with preserved renal nitric oxide (NO) production. This study examined CRD induced with repeated administration of puromycin aminonucleoside (PAN). SD PAN developed nephrotic range proteinuria (>1 g/24 h), and at 15 wk severe renal injury developed and the glomerular filtration rate (GFR) was reduced to ~10% of sham. Total NO production, renal NO synthase (NOS) activity, and renal neuronal (n) and medullary endothelial (e)NOS abundance were reduced in the SD PAN. WF PAN exhibited less severe initial proteinuria (>400 mg/24 h), which abated within weeks, whereas GFR was normal and injury was minimal at 15 wk. Total NO production and renal NOS activity and abundance were significantly elevated compared with SD PAN. NOS mRNA (nNOS, eNOS, and inducible NOS) was not altered in WF, whereas SD showed significant increases in NOS gene expression with PAN. In conclusion, WF showed resistance to a second model of CRD with maintained renal NOS activity compared with SD. glomerular filtration rate; proteinuria; nitric oxide deficiency

A series of experiments were conducted in juvenile and aging conscious rats to characterize the regulatory role of NO in the control of rodent renal hemodynamics. Tonically produced NO was more significant in the control or maintenance of renal perfusion in old rats compared to juvenile rats. However, basal and agonist-stimulated renal vascular NO production was not impaired by aging in normal, unstressed conscious rats. Furthermore, NO acted as a vasodilator that maintained normal low blood pressure and adequate renal perfusion.

Angiotensin II type 1 (ATI) stimulation and alpha(sub 1)-adrenoreceptors cause hypertension in chronically catheterized rats subjected to a prolonged NO blockade phase. The relaxing factor NO, derived from the endothelium, regulates blood pressure in a normal animal's basal state. Systematic hypertension that is attributed to NO blockade is associated with glomerular damage and glomerular capillary hypertension.

The role of endogenous angiotensin II (ANG II) in the renal hemodynamic responses to acute blockade of the endothelium-derived relaxing factor (EDRF) was investigated. It has been observed that renal responses to acute EDRF blockade were similar to the renal effects of ANG II. The ANG II inhibitors converting enzyme inhibitor and losartan were used to test renal functions in conscious, chronically catheterized rats. The results showed that ANG II does not mediate the renal responses to EDRF blockade.

The Wistar-Furth (WF) rat is protected against chronic renal disease (CRD) following 5/6th ablation/infarction vs. the Sprague-Dawley (SD) rat, and protection was associated with preserved renal nitric oxide (NO) production. This study examined CRD induced with repeated administration of puromycin aminonucleoside (PAN). SD PAN developed nephrotic range proteinuria (>1 g/24 h), and at 15 wk severe renal injury developed and the glomerular filtration rate (GFR) was reduced to ∼10% of sham. Total NO production, renal NO synthase (NOS) activity, and renal neuronal (n) and medullary endothelial (e)NOS abundance were reduced in the SD PAN. WF PAN exhibited less severe initial proteinuria (>400 mg/24 h), which abated within weeks, whereas GFR was normal and injury was minimal at 15 wk. Total NO production and renal NOS activity and abundance were significantly elevated compared with SD PAN. NOS mRNA (nNOS, eNOS, and inducible NOS) was not altered in WF, whereas SD showed significant increases in NOS gene expression with PAN. In conclusion, WF showed resistance to a second model of CRD with maintained renal NOS activity compared with SD. [ABSTRACT FROM AUTHOR]

Investigates the influences of the sympathetic nervous system and angiotensin II (ANG II) in maintenance of chronic nitric oxide blockade-induced hypertension. Effects of inhibition of alpha1-adrenergic receptors and the angiotensin type I receptor on renal function; Interactions between ANG II and alpha1-adrenoceptors.

The inbred obese Zucker (ZDF/Gmi, fa/fa) rat develops severe hyperglycemia and also exhibits severe renal disease. In this study, we compared the relative benefits of long-term treatment with angiotensin-converting enzyme inhibition (ACEI) to a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist. Four groups of obese inbred Zucker rats were studied over a 6-month observation period; untreated animals, rats treated with ACEI alone, rats treated with PPARgamma agonist alone, and rats treated with a combination of ACEI and PPARgamma agonist. PPARgamma agonist treatment normalized plasma glucose and led to massive increases in body weight. Both ACEI and PPARgamma agonist were effective in reducing the proteinuria and glomerular and tubular kidney damage. However, the PPARgamma agonist exerted superior renal protection compared with ACEI, in this model of spontaneously occurring chronic renal disease in the diabetic, obese inbred Zucker rat. Of note, although ACEI lowered blood pressure, there was no difference in glomerular blood pressure in any group at the end of the study. The glomerular filtration rate (GFR) was improved by ACEI with a borderline effect of PPARgamma agonist alone. A mild additive protection on GFR and tubulointerstitial damage was seen with the combination. Based on the literature it is likely that the superior protection by PPARgamma agonist versus glomerular and tubular damage as well as proteinuria extends beyond glycemic and lipidmic control and also reflects direct, protective intrarenal actions of the PPARgamma agonists.