Renin-angiotensin system in thyroid dysfunction in rats.

Abstract

Thyroid dysfunction produces marked cardiovascular responses; the renin-angiotensin system (RAS) is important in control of the cardiovascular system. We have measured changes in the plasma RAS and in angiotensin II (AT) receptors in experimentally hyperthyroid, euthyroid, or hypothyroid rats. Hyperthyroidism activated the plasma RAS, increasing plasma angiotensinogen by 85% after 7-day triiodothyronine (T3) treatment, plasma renin activity (PRA) by 47% and concentration by 52%, and plasma AT by 1.250%. Hypothyroidism reduced plasma angiotensinogen by 71%, PRA by 73%, and plasma AT by 81% without altering plasma renin concentration (PRC). Plasma aldosterone was reduced by 39% in hyperthyroid rats and by 95% in hypothyroid rats. AT receptors were characterized in heart, liver, adrenal gland, and kidney. Cardiac, liver, and kidney AT receptor densities increased in hyperthyroidism by 73, 113, and 75%, respectively; adrenal gland receptor density decreased by 39%. Similar results were observed in hypothyroidism except that adrenal gland receptor density was markedly increased by 205%. AT receptor subtypes were characterized in ventricular homogenates by the selective antagonist losartan. Hyperthyroidism markedly increased AT2-subtype density by 204% in left ventricle, and by 304% in right ventricle and decreased AT1-subtype density by 38% and 31% in left and right ventricles, respectively. AT2-subtype density increased by 168% in hypothyroid rats; AT1-subtype density was unchanged. Thyroid dysfunction causes significant changes in the RAS and in AT receptor density, especially of the AT2 subtype. Although a physiological function has not yet been reported for AT2 receptors, our results suggest that selective AT2-receptor antagonists may prove therapeutically useful in treatment of cardiovascular disease in thyroid dysfunction.