Submitted on September 13, 2007
Accepted on January 16, 2008
Tempol Improves Renal Hemodynamics and Pressure-Natriuresis in Hyperthyroid Rats
Juan Manuel Moreno1, Isabel Rodriguez Gomez2, Rosemary Wangensteen3, Miriam Alvarez-Guerra2, Juan de Dios Luna4, Joaquin Garcia-Estan5, and Felix Vargas6*
1 Servicio de Nefrologia. U. Experimental, Hospital Virgen de las Nieves, Granada, Spain
2 Facultad de Medicina, Departamento de Fisiologia, Universidad de Granada, Granada, Granada, Spain
3 Ciencias de la Salud, Universidad de Jaen, Jaen, Spain
4 Departamento de Bioestadistica, Universidad de Granada, Facultad de Medicina, Granada, Granada, Spain
5 Fisiologia, Universidad de Murcia, Murcia, Spain
6 Facultad de Medicina, Departamento de Fisiologia, Universidad de Granada, Granada, Spain
* To whom correspondence should be addressed. E-mail: fvargas{at}ugr.es.
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-treated (T4) rats. In another experiment, tempol was infused at 150 µmol/kg/h 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 RPP 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.
