Cardiac function of the diabetic renovascular hypertensive rat: effects of insulin and thyroid hormone treatment.
The influences of hypertension and hypothyroidism on diabetic cardiomyopathy are not clear. We studied this problem further by characterizing the effects of chronic triiodothyronine (T3) treatment on cardiac performance of diabetic renovascular hypertensive (RVH) rats. Hypertension was effected by clipping the left renal artery of Wistar-Kyoto (WKY) rats, and diabetes was induced 2 weeks later by streptozotocin (STZ; 55 mg/kg i.v.). The WKY strain was selected because it is relatively resistant to the cardiodepressant effects of diabetes, so that the influence of superimposed hypertension would be more apparent. Performance of working Krebs-Henseleit buffer perfused hearts was quantified by measuring left ventricular pressure and flow characteristics. The results showed that renovascular clipping caused a marked hypertension and left ventricular hypertrophy (LVH) but had no effect on perfused heart performance after 10 weeks. They also showed that diabetes during the final 8 weeks (i) caused a marked impairment in the performance of perfused hearts ex vivo of hypertensive rats but had no measurable effect in the normotensive WKY, (ii) had no effect on arterial pressure of either the normotensive or the hypertensive rats but reduced heart rate of hypertensive animals in vivo, and (iii) caused equivalent hyperglycemia, hypoinsulinemia, and hypothyroidism (depressed serum T3 and T4 levels) of hypertensive and normotensive rats. Treatment of diabetic RVH rats with T3 (10 micrograms.kg-1.day-1) in vivo was nearly as effective as insulin therapy (10 U.kg-1.day-1) in preventing the cardiac dysfunction ex vivo and was as effective as insulin therapy in preventing the bradycardia in vivo and the decline loss.(ABSTRACT TRUNCATED AT 250 WORDS)
Rodgers
R L
RL
Department of Pharmacology and Toxicology, University of Rhode Island, Kingston 02881-0809.
Davidoff
A J
AJ
Mariani
M J
MJ
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D006321:Heart / Q000503:physiopathology*; D006978:Hypertension, Renovascular / Q000188:drug therapy / Q000503:physiopathology*; D066298:In Vitro Techniques; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D011921:Rats, Inbred WKY; D013963:Thyroid Hormones / Q000627:therapeutic use*; D014284:Triiodothyronine / Q000627:therapeutic use
D007328:Insulin; D013963:Thyroid Hormones; D014284:Triiodothyronine