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This Article Full Text Full Text (PDF) All Versions of this Article: 291/5/R1376    most recent 00722.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wangensteen, R. Articles by Vargas, F. Search for Related Content PubMed PubMed Citation Articles by Wangensteen, R. Articles by Vargas, F.

NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Effects of chronic treatment with 7-nitroindazole in hyperthyroid rats

¹Departamento de Ciencias de la Salud, Universidad de Jaén, Jaén; ²Departamento de Fisiología, Facultad de Medicina, Granada; and ³Servicio de Nefrología, Unidad Experimental, Hospital Virgen de las Nieves, Granada, Spain

Submitted 11 October 2005 ; accepted in final form 31 May 2006

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), T₄50, T₄75 (50 or 75 µg thyroxine·rat^–1·day^–1, respectively), T₄50+7-NI, and T₄75+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 T₄75 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 T₄75 and T₄75+7-NI rats. T₄ 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 T₄75 group. Pentolinium produced a greater MAP decrease in the T₄75+7-NI than in the T₄75 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.

blood pressure; heart rate; pulse pressure; neuronal nitric oxide synthase inhibition