Published Online
on June 23, 2003

A more recent version of this article appeared on August 1, 2003

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Submitted on January 29, 2003
Revised on February 20, 2003

Increased Pressor Sensitivity to Chronic Nitric Oxide Deficiency in Hyperthyroid Rats

Isabel Rodríguez-Gómez; Juan Sainz; Rosemary Wangensteen; Juan Manuel Moreno; Juan Duarte; Antonio Osuna; and Félix Vargas^*

From Departamento de Fisiología, Facultad de Medicina (I.R.-G., J.S., R.W., J.M.M., F.V.); Departamento de Farmacología, Facultad de Farmacia (J.D.); and Servicio de Nefrologia, U. Experimental, Virgen de las Nieves (O.S.), Granada, Spain.

^* To whom correspondence should be addressed. E-mail: fvargas{at}ugr.es.

Abstract--We studied the effects of a possible interaction between partial nitric oxide deficiency and thyroid hormone excess on the long-term control of blood pressure (BP) and morphological and renal variables and examined the role of the renin-angiotensin system in the increased BP of this interaction. Eight groups (n=8 each) of male Wistar rats were used: a control group; 3 groups that were treated with thyroxine (50 µg/d), N^w-nitro-L-arginine methyl ester (L-NAME; subpressor dose, 1.5 mg · kg^-1 · d^-1), or thyroxine plus L-NAME; and another 4 similarly treated groups that received losartan (20 mg · kg^-1 · d^-1) in their drinking fluid. All treatments were maintained for 3 weeks. The time course of tail systolic BP was recorded once a week. At the end of the experimental period, we measured mean arterial pressure in conscious rats and assessed the morphological, metabolic, plasma, and renal variables. Thyroxine produced a mild BP increase from the second week of treatment and an increase in plasma angiotensin II and plasma nitrates/nitrites by the end of the study. Simultaneous administration of thyroxine and a subpressor dose of L-NAME produced a marked BP increase that reached significance from the first week of treatment. Losartan produced normotension in thyroxine-treated rats and attenuated the BP elevation in thyroxine+L-NAME-treated rats. Hyperthyroid rats showed relative renal and ventricular hypertrophy, absence of absolute left ventricular hypertrophy, and proteinuria. These alterations were not changed by losartan. We conclude that an impaired nitric oxide system might have a counterregulatory homeostatic role against the prohypertensive effects of thyroid hormone and that the renin-angiotensin system plays an important role in thyroxine+L-NAME hypertension.

Key words: blood pressure • hypertrophy, cardiac • losartan • nitric oxide • hyperthyroidism

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