Submitted on October 11, 2005
Accepted on May 31, 2006
Effects of Chronic Treatment with 7-Nitroindazole in Hyperthyroid Rats
Rosemary Wangensteen1, Isabel Rodriguez-Gomez2, Juan Manuel Moreno3, Miriam Alvarez-Guerra2, Antonio Osuna4, and Felix Vargas2*
1 Departamento de Ciencias de la Salud, Area de Fisiologia, Universidad de Jaen, Jaen, Spain
2 Facultad de Medicina, Departamento de Fisiologia, Universidad de Granada, Granada, Granada, Spain
3 Servicio de Nefrologia. Unidad Experimental, Hospital Universitario Virgen de las Nieves, Granada, Granada, Spain
4 Servicio de Nefrologia. Unidad Experimental, Hospital Universitario Virgen de las Nieves, Granada, Spain
* To whom correspondence should be addressed. E-mail: fvargas{at}ugr.es.
This study analyzed the contribution of neuronal nitric oxide synthase (nNOS) to the haemodynamic manifestations of hyperthyroidism. The effects on hyperthyroid rats of the chronic administration of 7-nitroindazole (7NI), an inhibitor of nNOS were studied. Six groups of male Wistar rats were used: control, 7NI (7NI, 30mg/kg/day by gavage), T450, T475 (50 or 75 µg thyroxine/rat/day, respectively), T450+7NI, and T475+7NI. All treatments were maintained for four weeks. Body weight, tail systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, SBP, pulse pressure (PP) and HR were measured in conscious rats, and morphologic, metabolic, plasma, and renal variables were determined. Expression of nNOS in the hypothalamus of T475 and control rats was analyzed by western blot. The response of mean arterial pressure (MAP) to pentolinium (10 mg/kg i.v.) was used to evaluate the sympathetic contribution to blood pressure (BP) in T475 and T475+7NI rats. T4 produced an increased hypothalamic nNOS expression and dose-related increases in BP, HR, and PP versus control rats. 7NI did not modify BP or any other hemodynamic variable in normal rats. However, 7NI produced a marked reduction in BP, HR, PP and food and water intake in both hyperthyroid groups and improved creatinine clearance in the T475 group. Pentolinium produced a greater MAP decrease in the T475-7NI than in the T475 group. In conclusion, the administration of 7NI attenuates the hemodynamic and metabolic manifestations of hyperthyroidism, suggesting that nNOS contributes to the hyperdynamic circulation of this endocrine disease by modulating sympathetic activity.
