Tempol improves renal hemodynamics and pressure natriuresis in hyperthyroid rats.
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 micromol/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 micromol.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 microeq.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.
Moreno
Juan Manuel
JM
Servicio de Nefrología, Unidad Experimental, Hospital Virgen de las Nieves, Granada, Spain.
Rodríguez Gómez
Isabel
I
Wangensteen
Rosemary
R
Alvarez-Guerra
Miriam
M
de Dios Luna
Juan
J
García-Estañ
Joaquín
J
Vargas
Félix
F
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D006980:Hyperthyroidism / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects*; D013113:Spin Labels; D013974:Thyroxine; D014655:Vascular Resistance / Q000187:drug effects
D000975:Antioxidants; D003497:Cyclic N-Oxides; D017382:Reactive Oxygen Species; D013113:Spin Labels; D013974:Thyroxine; C001803:tempol