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Chronic Tempol treatment prevents the renal vasoconstriction induced by a heme oxygenase inhibitor in Streptozotocin diabetic rats
Author(s) -
Rodríguez Francisca,
Lopez Bernardo,
Nieto Susana,
Salom Miguel G,
Hernandez Isabel,
Fenoy Francisco J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.164
Subject(s) - heme oxygenase , streptozotocin , medicine , endocrinology , oxidative stress , kidney , renal blood flow , vasoconstriction , renal circulation , diabetes mellitus , vasodilation , chemistry , heme , biochemistry , enzyme
Heme‐heme oxygenase (HO) system contributes to vasodilatory mechanisms in the renal circulation. HO‐1 isoform expression is highly increased by conditions associated to oxidative stress as those seen in diabetes. This study evaluated whether stimulation of HO by oxidative stress contributes to the renal hemodynamic changes observed in the streptozotocin (STZ) induced model of type‐1 diabetes mellitus (DM‐1). We tested the effects of the HO inhibitor Stannous Mesoporphyrin (SnMP 40 μmol/kg, iv), on blood pressure and renal blood flow, in control (n=8), STZ (65 mg/Kg iv; n=8), or STZ+Tempol (1mM in drinking water; n=5), in anesthetized rats. After two weeks, STZ treated hyperglycemic animals showed higher kidney weight /body weight ratio compared to control rats. Acute infusion of SnMP did not modify renal vascular resistance (RVR; mmHg/ml.min) in control (from 16±1 to 15±1), but it significantly increased RVR (from 19±2 to 31±8) in STZ rats, which was prevented by chronic Tempol treatment (from 23±2 to 25±2; p>0.05). Moreover, renal homogenates obtained from STZ rats (n=4) exhibited significantly higher HO‐1 protein expression and nytrotyrosine concentrations (an index of nitrosative stress), than those obtained from control animals (n=4). These results suggest that oxidative stress seems to be a key factor to stimulate vasodilatory actions mediated by HO in the diabetic kidney.