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The effect of experimental diabetes on drug induced responses in cardiac tissues of the rat

University of British Columbia

The effect of experimental diabetes mellitus on the response of isolated cardiac tissues to the 6 adrenergic agonist d,l isoproterenol and the cardiac glycoside ouabain was examined. The relationship between the duration of chemically induced diabetes and the response to these drugs was also investigated. Basal developed tension was not different in control vs.diabetic papillary muscles 7 days or 70 days after the induction of diabetes. Tissues from 7 day diabetic animals responded to d,l isoproterenol in a similar manner to tissues from control animals at each drug dose. There was a non-significant depression in the response of both papillary muscles and left atria from 70 day diabetic rats. This trend was evident throughout the dose-response curves. The basal rate of spontaneously beating isolated right atria from 7 day STZ diabetic rats was significantly depressed compared to control, while that of alloxan diabetic animals was depressed to a smaller degree. There was no difference in the maximum response of these-tissues to d,l isoproterenol. The basal rate was not different in atria from 70 day diabetic animals as compared to controls. Tissues from 70 day diabetic rats demonstrated a diminished response to d,l isoproterenol throughout the dose response curve however this depression was not statistically significant. There was no difference in tension development in left atria or papillary muscles at any time point. Seven days after the induction of diabetes both atria and papillary muscles demonstrated a nonsignificant depression of the ouabain dose response curve. Papillary muscles from 70 day diabetic animals displayed a significant depression in these dose response curves at ouabain concentrations greater than 10⁻⁵ M. Atria from six month diabetic rats demonstrated significantly depressed curves at concentrations greater than 3 x 10⁻⁵ M. Ouabain produces a monophasic dose response curve in left atria and a biphasic dose response curve in papillary muscles. Catecholamine release does not appear to be involved in these responses. Chronic alloxan and streptozotocin diabetes produces changes in the myocardium of rats characterized by a diminished inotropic response to the cardiac glycoside ouabain. This depression is not accompanied by a statistically significant decline in the maximum inotropic or chronotropic response to isoproterenol.

Text

2010-04-19

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http://hdl.handle.net/2429/23858

Pharmacology

University of British Columbia

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