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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/R867    most recent 00665.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Moreno, J. M. Articles by Vargas, F. Search for Related Content PubMed PubMed Citation Articles by Moreno, J. M. Articles by Vargas, F.

RENAL HEMODYNAMICS AND CARDIORENAL INTEGRATION

Tempol improves renal hemodynamics and pressure natriuresis in hyperthyroid rats

¹Servicio de Nefrología, Unidad Experimental, Hospital Virgen de las Nieves, Granada, Spain; Departamentos de ²Fisiología and ³Bioestadística, Facultad de Medicina, Granada, Spain; and ⁴Departamento de Ciencias de la Salud, Universidad de Jaén, Spain; and Departamento de Fisiología, Facultad de Medicina, Murcia, Spain

Submitted 13 September 2007 ; accepted in final form 16 January 2008

Hyperthyroidism in rats is associated with increased oxidative stress. These animals also show abnormal renal hemodynamics and an attenuated pressure-diuresis-natriuresis (PDN) response. We analyzed the role of oxidative stress as a mediator of these alterations by examining acute effects of tempol, a superoxide dismutase mimetic. The effects of increasing bolus doses of tempol (25–150 µmol/kg) on mean arterial pressure (MAP), renal vascular resistance (RVR), and cortical (CBF) and medullary (MBF) blood flow were studied in control and thyroxine (T₄)-treated rats. In another experiment, tempol was infused at 150 µmol·kg^–1·h^–1 to analyze its effects on the glomerular filtration rate (GFR) and on PDN response in these animals. Tempol dose dependently decreased MAP and RVR and increased CBF and MBF in control and T₄-treated rats, but the T₄ group showed a greater responsiveness to tempol in all of these variables. The highest dose of tempol decreased RVR by 13.5 ± 2.1 and 5.5 ± 1.2 mmHg·ml^–1·min^–1 in hyperthyroid (P < 0.01) and control rats, respectively. GFR was not changed by tempol in controls but was significantly increased in the hyperthyroid group. Tempol did not change the absolute or fractional PDN responses of controls but significantly improved those of hyperthyroid rats, although without attaining normal values. Tempol increased the slopes of the relationship between renal perfusion pressure and natriuresis (T₄+tempol: 0.17 ± 0.05; T₄: 0.09 ± 0.03 µeq·min^–1·g^–1·mmHg^–1; P < 0.05) and reduced 8-isoprostane excretion in hyperthyroid rats. These results show that antioxidant treatment with tempol improves renal hemodynamic variables and PDN response in hyperthyroid rats, indicating the participation of an increased oxidative stress in these mechanisms.

hyperthyroidism; glomerular filtration rate; renal blood flow