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-adrenergic stimulation in wild-type and phospholamban-deficient mouse hearts with altered thyroid conditions. Hypothyroidism was associated with significant decreases 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 and phospholamban-deficient mice exhibited similar increases in beta-myosin heavy 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 chain protein in the hyperthyroid hearts. The relative tissue level of phospholamban in wild-type hearts was increased (133%, P<0.01) in hypothyroidism, and decreased (69% P<0.01) in hyperthyroidism. when compared to euthyroid controls (100%). Similar increases and decreases in SR Ca2+-ATPase protein levels were observed between phospholamban-deficient and wild-type hearts in hyperthyroidism and hypothyroidism, respectively. The basal contractile state of wild-type and phospholamban-deficient hearts was significantly depressed in hypothyroidism. On the other hand, the basal contractile state of wild-type and phospholamban-deficient hearts was significantly increased in hyperthyroidism. During beta-agonist stimulation of wild-type hearts, the responses in the rates of contraction and relaxation were highest in the hypothyroid group. followed by the euthyroid, and lastly by the hyperthyroid groups. There was a close linear correlation between the magnitude of the contractile parameter responses and the phospholamban/SERCA2 ratios in these hearts, However, the phospholamban-deficient hypothyroid. euthyroid, and hyperthyroid hearts did not exhibit any responses to isoproterenol, indicating that the alterations in the thyroid states of these hearts do not influence the effects: of isoproterenol on cardiac function. These findings suggest that phospholamban is an important regulator of the heart's responses to beta-adrenergic stimulation under various thyroid states. (C) 1999 Academic Press.