Jose M. Haro

Effects of Methimazole on Low-Renal-Mass Hypertension; Changes in Blood Pressure and Pressor Responsiveness to Vasoconstrictors

The administration of the antithyroid drug methimazole to rats via drinking water prevented the development of hypertension that usually accompanies subtotal nephrectomy and saline drinking (1% NaCl). In methimazole-treated rats, elevated blood pressure induced 5 weeks previously returned to normotensive levels. Pressor responsiveness to angiotensin, vasopressin and norepinephrine in unanesthetized rats was studied after prevention of hypertension in control, low-renal-mass hypertensive (LRM) and low-renal-mass methimazole-treated (LRM-M) rats, and in the reversion study in LRM and LRM-M rats. In LRM rats, responsiveness to vasoconstrictors was increased, whereas responsiveness to vasoconstriction was clearly reduced in LRM-M rats after prevention and reversion studies. These results suggest that (a) thyroid hormones are required in the early and established phases of LRM hypertension, and (b) the decreased pressor responsiveness to vasoconstrictors may play a role in the prevention and reversion of this type of hypertension following methimazole administration. However, the changes in pressor responsiveness may also be secondary to the reduction in blood pressure.

Methimazole treatment reduces cardiac hypertrophy and mortality without a concomitant reduction in blood pressure in established Goldblatt two-kidney one clip hypertension

The effects of methimazole, and antithyroid drug, on blood pressure and other parameters were evaluated in the established phase of Goldblatt two-kidney one clip (G2K-1C) hypertension. Methimazole was administered via drinking water for five weeks, starting five weeks after hypertension had been induced. After this period of treatment, similarly high blood pressures were observed in methimazole-treated and non-treated G2K-1C rats, despite the fact that a hypothyroid state had been achieved in methimazole-treated rats. Methimazole-treated G2K-1C rats showed reductions in heart rate, ventricular weight, ventricular/body weight ratio and mortality in comparison with rats not treated with methimazole. These results clearly demonstrate that hypothyroidism induced by methimazole: a) does not reverse G2K-1C hypertension, but b) improves the rate of survival and c) reduces relative cardiac hypertrophy, possibly by the reduction in cardiac work observed in Goldblatt hypothyroid rats.

Effects on Renal Function and Digoxin-Like Immunoreactivity Produced by Methimazole in Low-Renal Mass Hypertension

This study evaluates the effects of methimazole, an antithyroid drug, on blood pressure, digoxin-like immunoreactive factor (DLIF) production and other variables related to salt and water metabolism in low-renal mass (LRM) hypertension. Drinking administration of methimazole (0.025%) from replacement of water by the 1% NaCl solution maintained the blood pressure of low-renal mass rats at normal levels during four weeks after hypertension induction. Serum and urinary excretion of DLIF were significantly increased in LRM rats with respect to controls; in all tests, the highest values of DLIF were found in LRM-methimazole treated (LRM-M) rats. Urinary excretion of DLIF showed positive correlations with diuresis and natriuresis in all three groups (control, LRM and LRM-M rats). However, the correlation between DLIF and sodium disappeared when both factors were expressed as a function of their concentrations. These results indicate that methimazole prevents LRM hypertension and suggest that DLIF might not represent the putative natriuretic hormone. Other findings were that methimazole-treatment reduced renal compensatory hypertrophy subsequent to subtotal nephrectomy, and did not modify the characteristic polyuria-polydypsia in this type of hypertension.

Urinary excretion of digoxin-like immunoreactive factor and arginine-vasopressin in rats after several osmotic loads

Urinary digoxin-like immunoreactive factor (DLIF), arginine-vasopressin (AVP) and other urinary parameters were investigated under normal conditions and after the i.p. injection of the following solutions: distilled water, isotonic and hypertonic NaCl, NaHCO3, KCl and urea, at a rate of 3 ml/100 g body weight. The measurement of digoxin-like immunoreactivity by two different radioimmunoassays showed that DLIF was stimulated by all volume loads regardless of the presence or absence of osmolar compounds. This dissociation between DLIF and urinary sodium excretion suggests that DLIF may not constitute the natriuretic hormone. Moreover, a dissociation between DLIF and AVP excretion also were found, which speaks against the hypothesis of a common mechanism of stimulation for both substances.

β-Adrenergic Reactivity in Conscious DOCA-Salt Hypertensive Rats

The endocrine (plasma renin activity, insulin and ADH) and hemodynamic responses (heart rate and mean arterial pressure) to isoprenaline infusion were examined in conscious deoxycorticosterone-salt hy