Cardiac and renal antioxidant enzymes and effects of tempol in hyperthyroid rats

• Published in: American journal of physiology: endocrinology and metabolism Vol. 289; no. 5; pp. E776 - E783
• Main Authors: Moreno, Juan Manuel, Gomez, Isabel Rodriguez, Wangensteen, Rosemary, Osuna, Antonio, Bueno, Pablo, Vargas, Felix
• Format: Journal Article
• Language: English
• Published: United States 01.11.2005
• Subjects: Animals; Antioxidants - pharmacology; Blood Pressure - drug effects; Catalase - metabolism; Cyclic N-Oxides - pharmacology; Dinoprost - analogs & derivatives; Dinoprost - urine; Glutathione Peroxidase - metabolism; Glutathione Reductase - metabolism; Heart Rate - drug effects; Hypertension - drug therapy; Hypertension - enzymology; Hypertension - etiology; Hyperthyroidism - complications; Hyperthyroidism - drug therapy; Hyperthyroidism - enzymology; Kidney - enzymology; Male; Malondialdehyde - blood; Myocardium - enzymology; Rats; Rats, Wistar; Spin Labels; Superoxide Dismutase - metabolism; Thyroxine - pharmacology
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00611.2004

2 Facultad de Medicina, Departamento de Fisiología y 1 Servicio de Nefrología, Unidad Experimental, Hospital Virgen de las Nieves, Granada; and 3 Departamento de Ciencias de la Salud, Universidad de Jaén, Jaén, Spain Submitted 27 December 2004 ; accepted in final form 31 May 2005 This study evaluated the activity of cardiac and renal antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR)] and whether chronic treatment with tempol, a cell membrane-permeable SOD mimetic, ameliorates the hypertension of hyperthyroidism. Two experiments were performed. In experiment I , the following four groups of male Wistar rats were used: control group and three groups that received thyroxine (T 4 ) at 10, 50, or 75 µg·rat –1 ·day –1 . In experiment II , tempol was orally administered (18 mg·kg –1 ·day –1 ) to control and T 4 -treated (75 µg·rat –1 ·day –1 ) rats. All treatments were maintained for 6 wk. Body weight, tail systolic blood pressure (BP), and heart rate were measured one time a week, and direct BP and morphological, metabolic, plasma, and renal variables were measured at the end of the experiment. Enzymatic activities were measured in renal cortex and medulla and right and left ventricles. In renal cortex, SOD activity was decreased in the T 4 -75 group, and there was a dose-related increase in CAT activity and decrease in GPX and GR activities in T 4 -treated groups. Activity of all antioxidant enzymes was reduced in left ventricle in T 4 -50 and T 4 -75 groups and in right ventricle in the T 4 -75 group. Tempol reduced BP, plasma malondialdehyde, and total urinary excretion of F 2 isoprostanes in hypertensive hyperthyroid rats but not in controls. Tempol did not improve cardiac hypertrophy, proteinuria, or creatinine clearance in hyperthyroid rats. In conclusion, the results obtained indicate that the activity of SOD, GPX, and GR in renal and cardiac tissues is decreased in hyperthyroidism and that antioxidant treatment with tempol ameliorates T 4 -induced hypertension. hyperthyroidism; hypertension; tempol; antioxidant enzymes; oxidative stress. Address for reprint requests and other correspondence: F. Vargas, Facultad de Medicina, Departamento de Fisiología, 18012, Granada, Spain (e-mail: fvargas{at}ugr.es )