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Cardiac function of the diabetic renovascular hypertensive rat: effects of insulin and thyroid hormone treatment
R L Rodgers1, A J Davidoff, M J Mariani
1Department of Pharmacology and Toxicology, University of Rhode Island, Kingston 02881-0809.
Insights
Hypertension and diabetes worsen diabetic cardiomyopathy. Triiodothyronine (T3) treatment improved cardiac function in diabetic hypertensive rats, similar to insulin therapy.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Metabolic Diseases
Background:
- Diabetic cardiomyopathy is a complex condition influenced by factors like hypertension and hypothyroidism.
- The specific impact of combined hypertension and diabetes on cardiac performance requires further elucidation.
- Wistar-Kyoto rats, relatively resistant to diabetes, were used to isolate the effects of superimposed hypertension.
Purpose of the Study:
- To investigate the effects of chronic triiodothyronine (T3) treatment on cardiac function in diabetic renovascular hypertensive (RVH) rats.
- To characterize the cardiac performance of diabetic RVH rats compared to normotensive diabetic rats.
- To assess the potential of T3 therapy in mitigating cardiac dysfunction in this model.
Main Methods:
- Induction of renovascular hypertension (RVH) by renal artery clipping in Wistar-Kyoto rats.
- Induction of diabetes using streptozotocin (STZ) in hypertensive and normotensive rats.
- Ex vivo assessment of cardiac performance using working Krebs-Henseleit buffer perfused hearts.
- In vivo monitoring of arterial pressure and heart rate.
- Measurement of serum glucose, insulin, T3, and T4 levels.
- Treatment of diabetic RVH rats with T3 or insulin.
Main Results:
- Renovascular clipping induced hypertension and left ventricular hypertrophy but did not affect baseline heart performance.
- Diabetes significantly impaired heart performance in hypertensive rats but not in normotensive rats.
- Diabetes reduced heart rate in hypertensive rats and caused hyperglycemia, hypoinsulinemia, and hypothyroidism in both groups.
- T3 treatment was nearly as effective as insulin in preventing cardiac dysfunction and bradycardia in diabetic RVH rats.
Conclusions:
- Hypertension exacerbates cardiac dysfunction in diabetic rats.
- Chronic T3 treatment effectively prevents cardiac dysfunction and bradycardia in diabetic hypertensive rats.
- T3 therapy presents a viable alternative to insulin for managing cardiac complications in diabetic hypertension.
Abstract:
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)