The effect of isoproterenol on phospholamban-deficient mouse hearts with altered thyroid conditions

The aim of the present study was to determine the effects of beta-adrenergi c stimulation in wild-type and phospholamban-deficient mouse hearts with al tered thyroid conditions. Hypothyroidism was associated with significant de creases in heart/body weight ratio in wild-type and phospholamban-deficient mice, whereas hyperthyroidism was associated with significant increases in heart/body weight ratio in both groups. Hypothyroid hearts of wild-type an d phospholamban-deficient mice exhibited similar increases in beta-myosin h eavy chain protein levels and decreases in alpha-myosin heavy chain protein levels. In hyperthyroidism, there were increases in the alpha-myosin heavy chain protein levels and these were similar in wild-type and phospholamban -deficient hearts. There were no detectable levels of beta-myosin heavy cha in protein in the hyperthyroid hearts. The relative tissue level of phospho lamban in wild-type hearts was increased (133%, P<0.01) in hypothyroidism, and decreased (69% P<0.01) in hyperthyroidism. when compared to euthyroid c ontrols (100%). Similar increases and decreases in SR Ca2+-ATPase protein l evels were observed between phospholamban-deficient and wild-type hearts in hyperthyroidism and hypothyroidism, respectively. The basal contractile st ate of wild-type and phospholamban-deficient hearts was significantly depre ssed in hypothyroidism. On the other hand, the basal contractile state of w ild-type and phospholamban-deficient hearts was significantly increased in hyperthyroidism. During beta-agonist stimulation of wild-type hearts, the r esponses in the rates of contraction and relaxation were highest in the hyp othyroid group. followed by the euthyroid, and lastly by the hyperthyroid g roups. There was a close linear correlation between the magnitude of the co ntractile parameter responses and the phospholamban/SERCA2 ratios in these hearts, However, the phospholamban-deficient hypothyroid. euthyroid, and hy perthyroid hearts did not exhibit any responses to isoproterenol, indicatin g that the alterations in the thyroid states of these hearts do not influen ce the effects: of isoproterenol on cardiac function. These findings sugges t that phospholamban is an important regulator of the heart's responses to beta-adrenergic stimulation under various thyroid states. (C) 1999 Academic Press.