Insulin, thyroid hormone, and heart function of diabetic spontaneously hypertensive rat.
Diabetes impairs cardiac performance more extensively in hypertensive rats than it does in nonhypertensive strains. A "low thyroid state" may contribute to the adverse cardiovascular effects of diabetes in spontaneously hypertensive rats (SHR). We tested this hypothesis by comparing the effects of thyroid hormone with those of insulin treatment on cardiac performance of diabetic SHR. Diabetes was induced with streptozotocin (45 mg/kg). Subsets of diabetic rats were treated with either insulin (10-20 units/kg/day) or triiodothyronine (8-10 micrograms/kg/day). Heart rate and systolic arterial pressure were obtained at weekly intervals. After 8 weeks, cardiac function was assessed using an isolated working heart preparation. Diabetes reduced arterial pressure and heart rate in vivo and markedly depressed cardiac performance under volume and pressure loading conditions ex vivo, confirming previous observations. As expected, insulin treatment prevented the bradycardia and depressor effect in vivo and the impairment of cardiac performance ex vivo caused by diabetes. The triiodothyronine treatment duplicated the effects of insulin on the hemodynamic measurements in vivo, and corrected nearly all depressed indexes of performance of diabetic SHR hearts ex vivo. Both treatment regimens successfully reduced 8-week mortality when compared with the untreated diabetic group. The results support the hypothesis that a low thyroid state may contribute to the cardiovascular dysfunction in diabetic SHR. Left ventricular hypertrophy may be an important factor in this phenomenon.
Davidoff
A J
AJ
Department of Pharmacology and Toxicology, University of Rhode Island, Kingston 02881.
Rodgers
R L
RL
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006321:Heart / Q000503:physiopathology*; D006339:Heart Rate; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007037:Hypothyroidism / Q000503:physiopathology; D007231:Infant, Newborn; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D009929:Organ Size; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013311:Streptozocin; D014284:Triiodothyronine / Q000627:therapeutic use*
D001786:Blood Glucose; D007328:Insulin; D014284:Triiodothyronine; D013311:Streptozocin