SARCOPLASMIC-RETICULUM GENE-EXPRESSION IN PRESSURE OVERLOAD-INDUCED CARDIAC-HYPERTROPHY IN RABBIT

Pressure overload (PO)-induced cardiac hypertrophy in rabbits has been utilized extensively to study alterations in systolic and diastolic f unctions of the heart. In earlier studies we showed that the levels of mRNA encoding two important sarcoplasmic reticulum (SR) proteins, the cardiac/slow-twitch muscle Ca2+-ATPase (SERCA2a) and phospholamban, w ere decreased in PO rabbit hearts. In this study, we analyzed the expr ession of the Ca2+-release channel (ryanodine receptor), calsequestrin , SERCA2a, and phospholamban in PO-induced cardiac hypertrophy after 2 , 4, 8, and 16 days of pulmonary artery banding. Northern blot and slo t blot analyses showed that the steady-state level of mRNA encoding th e cardiac ryanodine receptor, SERCA2a, and phospholamban was decreased significantly as early as 2 days after PO. In 16-day PO hearts, SERCA 2a mRNA was reduced to 7.9 +/- 3.4% (P < 0.05), phospholamban mRNA was reduced to 15.9 +/- 6.5% (P < 0.05), and ryanodine receptor mRNA was reduced to 49.2 +/- 23.6% (P < 0.05). In this study, calsequestrin mRN A levels were also reduced to 29.9 +/- 15.2% by day 16 (P < 0.05). ATP -dependent Ca2+ uptake was reduced to 78% (P < 0.05); in contrast, the steady-state formation of ATPase phosphoenzyme was reduced to 81% of control (P < 0.05) and Ca2+-ATPase protein was reduced to 78% of contr ol(P < 0.05) in crude SR vesicles or total muscle homogenate obtained from 16-day PO hearts. On the basis of these data, we propose that dec reases in the expression of SR proteins may contribute to dysfunctions seen in systolic and diastolic properties of the hypertrophied myocar dium.