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Myocardial performance of STZ-diabetic DOCA-hypertensive rats
1Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Insights
Deoxycorticosterone acetate (DOCA)-induced hypertension does not worsen myocardial dysfunction in streptozotocin (STZ)-diabetic rats. However, DOCA may affect glucose metabolism or insulin secretion.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Metabolic Disease Research
Background:
- Hypertension and diabetes are major risk factors for cardiovascular disease.
- Understanding the interplay between these conditions is crucial for developing effective treatments.
- Streptozotocin (STZ)-induced diabetes and deoxycorticosterone acetate (DOCA)-induced hypertension are common models for studying these pathologies.
Purpose of the Study:
- To investigate the combined effects of STZ-induced diabetes and DOCA-induced hypertension on myocardial performance.
- To determine the impact of DOCA-induced hypertension on the progression of diabetic cardiomyopathy.
- To explore potential alterations in glucose metabolism and insulin secretion under these experimental conditions.
Main Methods:
- Isolated working heart apparatus used to assess myocardial function in rats.
- Induction of experimental diabetes using streptozotocin (STZ) and hypertension using deoxycorticosterone acetate (DOCA).
- Measurements included blood pressure, heart rate, plasma glucose, insulin, cholesterol, triglycerides, and ventricular weight-to-body weight ratio.
Main Results:
- DOCA hypertension in nondiabetic rats led to increased cholesterol, decreased insulin, lower weight gain, and ventricular enlargement.
- STZ-diabetic rats showed time-dependent myocardial dysfunction, hyperglycemia, hypoinsulinemia, bradycardia, and ventricular enlargement.
- STZ-diabetic DOCA-hypertensive rats exhibited similar myocardial dysfunction but greater ventricular enlargement and less severe hyperglycemia compared to normotensive diabetic rats.
Conclusions:
- DOCA-induced hypertension does not exacerbate myocardial dysfunction in STZ-diabetic rats.
- DOCA-induced hypertension may influence glucose metabolism or insulin secretion independently.
- The study highlights the complex interactions between hypertension and diabetes on cardiac health.
Abstract:
Myocardial performance of streptozotocin (STZ)-diabetic deoxycorticosterone acetate (DOCA)-hypertensive rats was examined using the isolated working heart apparatus at various time periods after induction of the experimental diseases. Blood pressure, pulse rate, and plasma levels of glucose, insulin, cholesterol, and triglycerides, as well as ventricular weight-to-body weight ratio, were also determined. In nondiabetic rats it was found that DOCA hypertension was associated with an increase in plasma cholesterol, a decrease in circulating insulin level, lower weight gain, and ventricular enlargement compared with control rats. Diabetic rats developed myocardial dysfunction in a time-dependent manner and exhibited hyperglycemia, hypoinsulinemia, bradycardia, and ventricular enlargement. Compared with the normotensive diabetic animals, STZ-diabetic DOCA-hypertensive rats showed a similar magnitude of myocardial dysfunction and a greater degree of ventricular enlargement, but significantly less severe hyperglycemia. It is concluded that DOCA-induced hypertension does not aggravate the severity of myocardial dysfunction developed in STZ-diabetic rats. It is also suggested that DOCA may have an action on glucose metabolism either directly or via an effect on insulin secretion.