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Chronic tempol treatment attenuates the renal hemodynamic effects induced by a heme oxygenase inhibitor in streptozotocin diabetic rats.

Authors: Rodriguez, F  Lopez, B  Perez, C  Fenoy, FJ  Hernandez, I  Stec, DE  Li Volti, G  Salom, MG 
Citation: Rodriguez F, etal., Am J Physiol Regul Integr Comp Physiol. 2011 Nov;301(5):R1540-8. doi: 10.1152/ajpregu.00847.2010. Epub 2011 Aug 17.
Pubmed: (View Article at PubMed) PMID:21849637
DOI: Full-text: DOI:10.1152/ajpregu.00847.2010

Heme oxygenase-1 (HO-1) is induced by oxidative stress and plays an important role in protecting the kidney from oxidant-mediated damage in the streptozotocin (STZ) rat model of type-1 diabetes mellitus (DM-1). HO-derived metabolites, presumably carbon monoxide (CO), mediate vasodilatory influences in the renal circulation, particularly in conditions linked to elevated HO-1 protein expression or diminished nitric oxide (NO) levels. We tested the hypothesis that diabetes increases oxidative stress and induces HO-1 protein expression, which contributes to regulate renal hemodynamics in conditions of low NO bioavailability. Two weeks after the induction of diabetes with STZ (65 mg/kg iv), Sprague-Dawley rats exhibited higher renal HO-1 protein expression, hyperglycemia, and elevated renal nitrotyrosine levels than control normoglycemic animals. In anesthetized diabetic rats, renal vascular resistance (RVR) was increased, and in vivo cortical NO levels were reduced (P < 0.05) compared with control animals. Acute administration of the HO inhibitor Stannous mesoporphyrin (SnMP; 40 mumol/kg iv) did not alter renal hemodynamics in control rats, but greatly decreased glomerular filtration rate and renal blood flow, markedly increasing RVR in hyperglycemic diabetic rats. Chronic oral treatment with the SOD mimetic tempol prevented the elevation of nitrotyrosine, the HO-1 protein induction, and the increases in RVR induced by SnMP in the diabetic group, without altering basal NO concentrations or RVR. Increasing concentrations of a CO donor (CO-releasing molecule-A1) on pressurized renal interlobar arteries elicited a comparable relaxation in vessels taken from control or diabetic animals. These results suggest that oxidative stress-induced HO-1 exerts vasodilatory actions that partially maintain renal hemodynamics in uncontrolled DM-1.

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RGD ID: 10755581
Created: 2016-02-02
Species: All species
Last Modified: 2016-02-02
Status: ACTIVE



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