CARDIAC ANGIOTENSIN RECEPTORS IN EXPERIMENTAL HYPERTHYROIDISM IN DOGS

Objective: The aim was to define the changes in angiotensin II receptors and the plasma renin-angiotensin system in experimental hyperthyroidism in dogs. Methods: Hyperthyroidism was induced in dogs by subcutaneous injection of triiodothyronine (T3; 1 mg.kg-1.d-1 for 14 d; group T); control dogs received saline (group C). Plasma angiotensin II (AII), angiotensinogen, renin activity and concentration, and angiotensin II receptors in left ventricle, right atrium, thoracic aorta, adrenal gland, and liver were measured. Results: T3 treatment caused tachycardia, increased heart weight, hypertrophy of the circumflex and septal coronary arteries, increased plasma renin activity [C=1.6(SEM 0.2), T=9.8(2.8) ng angiotensin I.ml-1.h-1], plasma renin concentration [C=13.0(3.7), T=34.5(5.6) ng angiotensin I.ml-1.h-1], and plasma All [C=23(3), T=104(5) pg.ml-1], while plasma angiotensinogen did not change. There were no significant changes in adrenal gland and right atrial angiotensin II receptor densities; increases were measured in the left ventricle [C=0.33(0.06), T=0.75(0.12) pmol.g-1 tissue], thoracic aorta [C=0.19(0.02), T=0.28(0.03) pmol.g-1 tissue], and liver [C=8.4(1.2), T=12.9(1.7) pmol.g-1 tissue]. The relative affinities of the left ventricular angiotensin II receptor for angiotensin peptides (obtained from displacement assays) were: Sar1, Ile8-AII > AII > angiotensin III > angiotensin I > hexapeptide > pentapeptide. Conclusions: Experimental hyperthyroidism in dogs results in activation of the plasma renin-angiotensin system and up regulation of left ventricular, aortic, and liver angiotensin II receptors.