UBC Theses and Dissertations
Alterations in cardiac responses to adrenergic agonists and in circulating thyroid hormones in alloxan induced diabetic rats Bi, Yi Jia
The effects of adrenergic agonists in the heart were investigated in isolated cardiac tissues and in the whole heart in 8 week diabetic and age-matched control rats by measuring contractile force following administration of PE in presence of timolol, or ISO. Plasma thyroid hormones as well as insulin, glucose and triglyceride was measured. The contractile force of the isolated cardiac tissues was measured in tissue baths under physiological conditions and results expressed by construction of concentration response curves to adrenoceptors agonists, 10⁻⁹ to 10⁻⁴ M for ISO and 10⁻⁷ to 10⁻³ M for PE. The contractile force of the whole heart was measured as left ventricular systolic pressure, without pharmacological intervention and following administration of 10⁻⁶ M PE or 10⁻⁵ M ISO in the perfusate. The hearts were clamp-frozen at 0, 15 and 30 seconds, and 1, 4 minutes following adrenoceptor agonists for measurement of cAMP levels. Cardiac cAMP was measured in the frozen ventricles by employing Amersham commercial SPA kit while protein was measured by using Bio-Rad Dye method. The tissue content of cAMP was expressed as pmol cAMP/mg protein. It was found that the contractile response to PE was increased whereas that to ISO was decreased significantly in diabetic papillary muscle but not the left atria from the same group of animals. The chronotropic effect of PE was increased and that of ISO was decreased significantly in diabetic right atria. The contractile force of the whole heart preparation was increased in diabetic hearts following both adrenoceptor agonists and the increased positive inotropic effect of ISO was accompanied by an increase in cAMP levels. In all of the diabetic animals, the thyroid hormone levels were significantly lower than those of the controls. These findings confirmed that the cardiac alterations and the low thyroid state in ALX-induced diabetic rats are similar to those that occur in STZ-induced diabetic rats although further studies would be needed to reveal the interrelation between the diabetesassociated low thyroid state and diabetic cardiomyopathy.
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