Role of beta adrenoceptors in the hypertrophic response to thyroxine.
The ability of beta-adrenoceptor blockade to reduce the hypertrophic response to thyroxine (T4, 0.5 mg/kg per day, s.c.) was tested in New Zealand white rabbits. Two beta-adrenergic blocking agents, one a full antagonist (propranolol, 9.6 mg/kg per day) and the other a partial agonist (pindolol, 0.96 mg/kg per day) were administered in combination with T4 in an effort to reduce myocardial hypertrophy. A 3 and 16 day group were generated to test the time course of the hypertrophic and receptor responses. Coronary blood flow was measured using radioactive microspheres, and beta-adrenoceptor number and affinity were measured using 125I(-) pindolol as the radioligand. T4 increased coronary blood flow to 1.95 times control values in the 3 day group and 2.2 times control levels in the 16 day group; beta-adrenoceptor number was increased similarly in 3 and 16 day groups to 1.9 times control Bmax levels. Heart weight (HW) to body weight (BW) ratios were significantly increased in only the 16 day group to 1.22 and 1.61 times control, respectively. Treatment with propranolol + T4 blunted the coronary blood flow increase, but receptor upregulation occurred to the same extent as with either substance alone. The HW/BW was increased to 1.49 times control. Pindolol + T4 did not decrease coronary blood flow but blocked beta-adrenoceptor upregulation. The HW was reduced to control levels and the HW/BW ratio was 1.40 times control and significantly decreased from T4 alone. Thus, pindolol was effective in reducing the hypertrophic response to T4, whereas propranolol was only moderately effective in doing so.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854-5635.
Weiss
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced*; D003326:Coronary Circulation / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007457:Iodine Radioisotopes; D009929:Organ Size / Q000187:drug effects; D010869:Pindolol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013974:Thyroxine / Q000494:pharmacology*
D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D010869:Pindolol; D013974:Thyroxine