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Myocardial function characteristics, response to isoproterenol, and calcium uptake activity in rats pretreated with thyroid hormones

University of British Columbia

Thyroid hormone pretreatment altered rat myocardial function curve characteristics, showed no effect on the sensitivity of the heart to isoproterenol, and did not change the calcium uptake activity into sarcoplasmic reticulum vesicles. Hearts from rats treated either for 3 days with L-triiodothyronine (T3) or for 7 days with L-thyroxine (T4) were subjected to changes in atrial filling pressure from 5 cm of water to 22.5 cm of water on the modified Neely working heart apparatus. Thyroid hormone pretreated rat hearts showed increased pressure and rate parameter measurements over their vehicle pretreated counterparts at all atrial filling pressures. Time to peak pressure was not significantly lowered, but relaxation time for the T3 treated rat hearts was significantly lower than that of control rat hearts at all atrial filling pressures. T4 hearts had shorter relaxation times than did control hearts at the lower filling pressures, but at filling pressures over 15 cm of water the TM relaxation times approached those of control. At 17.5 cm of water filling pressure T3 hearts had significantly shorter relaxation times than did T4 hearts. Measurement of the total pulse period or total contraction time showed similar trends, however in this case T3 hearts had shorter total pulse periods than T4 hearts at all atrial filling pressures over. 15 cm of water. Areas were measured under the left ventricular pressure curve. None of the area measurements for thyroid hormone pretreated hearts were significantly different from control. Isoproterenol dose response curves were also obtained from the working hearts of all experimental groups. T3 hearts consistently showed higher values in left ventricular developed pressure, rate of pressure development and rate of relaxation than did control and T4 hearts even before isoproterenol was administered. T4 hearts had values not different from control values at any dose of isoproterenol in the measurement of any parameter. Time to peak pressure and relaxation time did not vary between groups. At a sub-maximal dose of isoproterenol T3 hearts had a significantly decreased total time of contraction. Area under the curve from peak pressure back to baseline was significantly increased over control levels for T3 hearts at two low doses of isoproterenol. Total area under the curve was not changed in thyroid hormone treated hearts. In order to account for the wide difference in baseline values for all the parameters, the data were expressed in terms of percent maximum response, and the pD2 values (negative log ED50) were calculated. The pD2 values so obtained were not different between the groups. Calcium uptake activity into cardiac sarcoplasmic reticulum was measured. No differences were seen between the experimental groups. Thus, while performance of the rat heart in terms of left ventricular pressure, and rate of pressure rise and fall was increased by thyroid hormone pretreatment, no change in sensitivity of the heart to isoproterenol could be shown. There was also no difference in calcium uptake activity. We speculate that changes in the calcium sensitivity of the contractile proteins in the rat heart may be responsible for the increased myocardial contractility seen after thyroid hormone pretreatment. The lack of change in sensitivity to isoproterenol of the thyroid pretreated hearts could then be explained by the steric hindrance of this enhanced calcium sensitivity by catecholamine-induced phosphorylation of the troponin I subunit by cyclic AMP dependent protein kinase. Calcium uptake activity was unchanged by thyroid hormone pretreatment. If the augmented contractility observed in thyroid hormone pretreated hearts over the function curve was due to increased sensitivity of these hearts to an unchanged concentration of calcium within the cell, this similarity of calcium uptake activity would be expected.

Text

2010-04-19

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http://hdl.handle.net/2429/23872

Pharmacology

University of British Columbia

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