Adrenoceptor-mediated cardiac and vascular responses in hypothyroid rats.
This study has investigated adrenoceptor-mediated responses and beta-adrenoceptors in neonatal-onset hypothyroidism in rats. Four groups of adult rats were studied: controls, neonatal-onset uncorrected hypothyroidism (continuous oral methimazole treatment) and after chronic triiodothyronine (T3) replacement of these rats at either 25 or 100 micrograms/kg/day for 8 weeks beginning at 12 weeks of age. Hypothyroid rats were 61% smaller with an 18% decrease in heart rate; food and water intake were reduced to 43% and 52%, respectively; O2 consumption was reduced to 20% and rectal temperature was 2.9 degrees lower. T3 administration increased body weight to 60-62% of controls; metabolic changes were reversed; but tachycardia and cardiac hypertrophy (60-120% increases) resulted. The positive inotropic responses to the selective alpha 1-adrenoceptor agonist, phenylephrine, in left ventricular papillary muscles were abolished; the beta 1-adrenoceptor agonist, noradrenaline, was significantly less potent as an inotropic compound in isolated cardiac tissues from hypothyroid rats. The potency of phenylephrine to contract thoracic aortic rings was reduced in hypothyroid rats. These changes in alpha- and beta-adrenoceptor mediated responses were reversed by T3 administration. Both beta 1- and beta 2-adrenoceptor densities were increased in the hypothyroid left ventricle; T3 administration further increased beta 1-adrenoceptor density. We conclude that neonatal hypothyroidism produces pronounced physiological responses, changes in adrenoceptor-mediated responses and an increased ventricular beta 1-adrenoceptor density. T3 replacement reversed the changes in cardiac responses and metabolic parameters, except body weight, but produced cardiac symptoms of hyperthyroidism (tachycardia, hypertrophy as well as an increased beta 1-adrenoceptor density).
Brown
L
L
Department of Physiology and Pharmacology, University of Queensland, Australia.
Nankervis
R
R
Kerr
D
D
Sernia
C
C
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D008713:Methimazole; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010210:Papillary Muscles / Q000378:metabolism* / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D014284:Triiodothyronine / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D014284:Triiodothyronine; D010656:Phenylephrine; D008713:Methimazole; D002122:Calcium Chloride; D009638:Norepinephrine