Cardiac beta-adrenoceptor changes in experimental hyperthyroidism in dogs.
1. Triiodothyronine (T3; 1.0 mg/kg per day subcutaneously) was administered to 10 dogs for 14 days; 10 saline-treated dogs served as controls. T3-treated dogs showed the expected physiological responses of hyperthyroidism; further, chronotropic responses to isoprenaline in vivo were significantly increased in T3-treated dogs. 2. Beta-adrenoceptor subtype density was measured in membrane preparations by displacement of 125I-iodocyanopindolol binding by the selective beta 2-adrenoceptor antagonist, ICI 118, 551. T3 treatment led to a 93% increase in right atrial beta 1-adrenoceptor density and a 141% increase in left ventricular beta 1-adrenoceptor density; beta 2-adrenoceptor densities in right atrial, left ventricular and lung membranes were unchanged. 3. T3-treatment did not change basal or maximally stimulated adenylate cyclase activities in left ventricular membranes. 4. Thus, the cardiovascular changes in experimental hyperthyroidism in dogs were accompanied by an increased chronotropic response in vivo to isoprenaline and an increased beta 1-adrenoceptor density in atrial and ventricular membranes. However, there was no corresponding change in basal or maximal responsiveness of adenylate cyclase in ventricular membranes.
Hoey
A
A
Department of Physiology and Pharmacology, University of Queensland, St Lucia, Australia.
Brown
L
L
Marchant
C
C
Atwell
R
R
Sernia
C
C
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006980:Hyperthyroidism / Q000378:metabolism* / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases; D007545:Isoproterenol