Influence of the low thyroid state in diabetes mellitus on cardiac function and inotropic responsiveness to alpha 1-adrenoceptor stimulation: comparison with the role of hypothyroidism alone.
The hypothyroid state accompanying diabetes mellitus has been suggested to be partly responsible for the diabetes-induced metabolic, hemodynamic, and pharmacological cardiovascular changes. We assessed the effectivity of streptozotocin (STZ) to induce diabetes mellitus and a hypothyroid state. Furthermore, we investigated the influence of diabetes and hypothyrodism on cardiac function and the inotropic responsiveness to the alpha 1-adrenoceptor agonist cirazoline in isolated perfused hearts. Fasted or nonfasted Wistar rats were made diabetic with STZ 20, 40 or 60 mg/kg intravenously (i.v.). Another group was made hypothyroid by addition of 6-n-propyl-2-thiouracil (PTU) to their drinking water. Rats receiving PTU became hypothyroid, whereas rats receiving STZ became simultaneously diabetic and hypothyroid. Basal functional parameters obtained in isolated perfused hearts were not influenced by diabetes, whereas maximal contractility was reduced in hearts obtained from hypothyroid animals. Cardiac inotropic responses to cirazoline were increased in diabetic rats, whereas responses in hypothyroid rats were not different from those in hearts obtained from control animals. Although diabetes mellitus and hypothyroidism are associated with various similar metabolic and haemodynamic parameters, the increased inotropic response to alpha 1-adrenoceptor stimulation as observed in isolated perfused hearts of diabetic rats cannot be explained by the decrease in serum thyroxine levels.
Department of Pharmacotherapy, University of Amsterdam, Academic Medical Centre, The Netherlands.
O H
OH
Beenen
M
M
Pfaffendorf
P A
PA
van Zwieten
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D003326:Coronary Circulation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D005215:Fasting; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006339:Heart Rate; D007037:Hypothyroidism / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D011441:Propylthiouracil; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000494:pharmacology; D013974:Thyroxine / Q000097:blood; D017725:Ventricular Pressure / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D013311:Streptozocin; D011441:Propylthiouracil; D013974:Thyroxine; C014282:cirazoline