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Sensitivity changes to inotropic agents in rabbit atria after chronic experimental diabetes
1Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Canadian Journal of Physiology and Pharmacology
|December 1, 1988
Summary
Experimental diabetes in rabbits alters heart muscle sensitivity to certain drugs over time. Long-term diabetes (15 weeks) decreases sensitivity to beta-adrenergic agents and ouabain, independent of thyroid hormones.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Diabetes mellitus can affect cardiovascular function.
- The impact of experimental diabetes on cardiac contractility and drug sensitivity requires further elucidation.
Purpose of the Study:
- To investigate the effect of experimental diabetes on the sensitivity of isolated rabbit atrial strips to various inotropic agents.
- To compare the effects of short-term (4 weeks) versus long-term (15 weeks) diabetes.
Main Methods:
- Rabbits were made diabetic using alloxan.
- Isolated left atrial strips were used to assess sensitivity to isoproterenol, noradrenaline, ouabain, forskolin, phenylephrine, and calcium chloride.
- Concentration-response curves were generated to determine drug sensitivity.
Main Results:
- After 4 weeks of diabetes, no significant changes in sensitivity to isoproterenol or ouabain were observed.
- After 15 weeks of diabetes, a decreased sensitivity to beta-adrenergic stimulation (isoproterenol, noradrenaline) and ouabain was detected.
- No significant changes in sensitivity to alpha-adrenergic stimulation (phenylephrine) or calcium chloride were found.
- Serum thyroid hormone levels remained unchanged in alloxan-diabetic rabbits, unlike in streptozotocin-diabetic rats.
Conclusions:
- Long-term experimental diabetes in rabbits impairs cardiac sensitivity to beta-adrenergic agonists and cardiac glycosides.
- These deleterious effects appear to be independent of changes in serum thyroid hormone levels.
- Differences in alpha-adrenergic sensitivity between diabetic rats and rabbits may relate to thyroid hormone levels.