Thyroidectomy of SHR: effects on ventricular relaxation and on SR calcium uptake activity

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.

Ventricular relaxation of diabetic spontaneously hypertensive rat.

“…The T r variable did not correlate as well because it differed between nondiabetic SHR and WKY rat groups, whereas the SR Ca 2+ uptake activity did not (Tables 4 and 5). In contrast to the results of the previous report, 16 in the present study LV-dP/dt varied with P^A , . However, the former variable is inconsistent and difficult to interpret, largely because of its dependence on the configuration of the pressure wave.…”

“…A recent report from this laboratory suggested that the ratio P^A , can serve as an index of load-dependent relaxation in the ejecting ventricle. 16 As expected, the value of Pmu/Ar in the present study correlated with the rate of SR Ca 2+ uptake between experimental groups (Table 5, Figures 2 and 3). The T r variable did not correlate as well because it differed between nondiabetic SHR and WKY rat groups, whereas the SR Ca 2+ uptake activity did not (Tables 4 and 5).…”

“…Chronically, T 3 probably increases the rate of SR Ca 2+ uptake by accelerating the synthesis of Ca 2+ -Mg 2+ ATPase enzyme molecules, and hypothyroidism has opposite effects on these measurements. 45 The data from our study ( Figure 3) and those of a previous report 16 are consistent with such an effect of thyroid state in diabetic SHR.…”

“…The area under the LVP wave over T r (A r ) was used to quantify pressure load-dependent relaxation. 16 For each heart and at each pressure load, P,^ was plotted against A T ; the slope of the regression line through the four points was used as the relaxation index (P^JA^). Preliminary studies showed that sampling and averaging of successive pressure waves was unnecessary because the variability between waves never exceeded 0.1%.…”

Effect of thyroid hormone on slow calcium channel function in cultured chick ventricular cells.

“…These findings have led to the hypothesis that enhancement of myocardial contractility by thyroid hormones is the result of increased cardiac myosin ATPase ac-tivity. However, thyroid hormone has also been reported to alter Ca uptake by sarcoplasmic reticulum (9)(10)(11)(12)(13)(14), to stimulate plasma membrane Ca-ATPase activity (4,15,16), and also to increase the numbers of sarcolemmal sodium pump sites (17)(18)(19). Therefore, the mechanisms by which myocardial contractility is enhanced in response to thyroid hormone appear to include altered Ca handling by sarcoplasmic reticulum and also changes in sarcolemmal membrane function that would directly influence the excitation-contraction coupling process.…”