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Thyroidectomy of SHR: effects on ventricular relaxation and on SR calcium uptake activity
Insights
Hypothyroidism impairs cardiac relaxation and calcium uptake in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Combined hypothyroidism and SHR exacerbates these cardiac dysfunctions, highlighting a significant correlation between mechanical relaxation and SR calcium uptake.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Molecular Cardiology
Background:
- Ventricular hypertrophy and hypothyroidism both impair cardiac muscle relaxation and sarcoplasmic reticulum (SR) calcium uptake.
- Previous studies indicated hypothyroidism does not reverse ventricular hypertrophy in spontaneously hypertensive rats (SHR).
Purpose of the Study:
- To investigate the effects of induced hypothyroidism on cardiac relaxation and SR calcium uptake in SHR and Wistar-Kyoto rat (WKY) controls.
- To determine if hypothyroidism exacerbates cardiac dysfunction in SHR.
Main Methods:
- Thyroidectomy was performed for 8 weeks on SHR and WKY rats.
- Cardiac relaxation was assessed in ejecting hearts by measuring left ventricular pressure changes.
- SR calcium uptake activity was measured in vitro.
Main Results:
- Euthyroid SHR exhibited impaired relaxation and reduced SR calcium uptake compared to euthyroid WKY rats.
- Thyroidectomy similarly reduced relaxation and SR calcium uptake in both SHR and WKY strains.
- The most depressed cardiac function was observed in the hypothyroid SHR group.
Conclusions:
- Hypothyroidism significantly impairs cardiac relaxation and SR calcium uptake in both normotensive and hypertensive rat models.
- The combination of SHR and hypothyroidism leads to the most severe cardiac dysfunction.
- A strong correlation exists between ex vivo mechanical relaxation and in vitro SR calcium uptake rates.
Abstract:
Ventricular hypertrophy and hypothyroidism are each characterized by impaired cardiac muscle relaxation and sarcoplasmic reticulum (SR) calcium uptake activity. A previous report also showed that hypothyroidism does not reverse ventricular hypertrophy (left-to-right ventricular weight ratios) of spontaneously hypertensive rats (SHR). We characterized the effects of thyroidectomy of 8 wk duration on relaxation of ejecting hearts and on SR calcium uptake activity from SHR and nonhypertrophic Wistar-Kyoto rat (WKY) controls. Relaxation was quantified by plotting maximum left ventricular pulse pressure (Pmax) vs. the area under the falling phase of the left ventricular pressure wave at three different pressure loads. Ventricles of euthyroid SHR were characterized by impaired relaxation and depressed SR calcium uptake activity compared with those of euthyroid WKY, confirming earlier studies. Thyroidectomy reduced ventricular relaxation and SR calcium uptake activities to about the same extent in SHR and WKY strains so that these measurements were most depressed in the SHR hypothyroid group. When all groups were considered, the extent of mechanical relaxation ex vivo and the rate of SR calcium uptake in vitro were well correlated.