Effects of chronic treatment with 7-nitroindazole in hyperthyroid rats.
This study analyzed the contribution of neuronal nitric oxide synthase (nNOS) to the hemodynamic manifestations of hyperthyroidism. The effects on hyperthyroid rats of the chronic administration of 7-nitroindazole (7-NI), an inhibitor of nNOS, were studied. Six groups of male Wistar rats were used: control, 7-NI (30 mg.kg-1.day-1 by gavage), T(4)50, T(4)75 (50 or 75 microg thyroxine.rat-1.day-1, respectively), T(4)50+7-NI, and T(4)75+7-NI. All treatments were maintained for 4 wk. 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 morphological, metabolic, plasma, and renal variables were determined. Expression of nNOS in the hypothalamus of T(4)75 and control rats was analyzed by Western blot analysis. The response of mean arterial pressure (MAP) to pentolinium (10 mg/kg iv) was used to evaluate the sympathetic contribution to BP in T(4)75 and T(4)75+7-NI rats. T(4) produced an increased hypothalamic nNOS expression and dose-related increases in blood pressure (BP), HR, and PP vs. control rats. 7-NI did not modify BP or any other hemodynamic variable in normal rats. However, 7-NI produced a marked reduction in BP, HR, PP, and food and water intake in both hyperthyroid groups and improved creatinine clearance in the T(4)75 group. Pentolinium produced a greater MAP decrease in the T(4)75+7-NI than in the T(4)75 group. In conclusion, administration of 7-NI attenuates the hemodynamic and metabolic manifestations of hyperthyroidism, suggesting that nNOS contributes to the hyperdynamic circulation of this endocrine disease by modulating sympathetic activity.
Wangensteen
Rosemary
R
Departamento de Ciencias de la Salud, Universidad de Jaén, and Servicio de Nefrología, Unidad Experimental, Hospital Virgen de las Nieves, Granada, Spain.
Rodríguez-Gómez
Isabel
I
Moreno
Juan Manuel
JM
Alvarez-Guerra
Miriam
M
Osuna
Antonio
A
Vargas
Félix
F
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006980:Hyperthyroidism / Q000188:drug therapy*; D007031:Hypothalamus / Q000378:metabolism; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000097:blood
D004791:Enzyme Inhibitors; D007191:Indazoles; D014508:Urea; D003404:Creatinine; D052248:Nitric Oxide Synthase Type I; C080122:7-nitroindazole