Sarcolipin, a homologue of phospholamban, regulates Ca2+ uptake through the interaction with sarcoplasmic reticulum Ca2+ ATPase (SERCA) and is predominantly expressed in the atrial muscle. Although the atrial chamber-specific expression of sarcolipin could be primarily regulated at the transcriptional level, the transcriptional regulation remains poorly understood. Since mechanical stress plays an important role in transcriptional regulation of a gene involved in cardiac hypertrophy and remodeling, we generated left-sided or right-sided pressure-overload models by transverse aortic constriction (TAC) in ddY mice or by monocrotaline administration in Wistar rats, respectively. TAC significantly decreased the expression of sarcolipin, SERCA2a, and phospholamban mRNAs in the left atrium (LA) than those in the right atrium (RA). By contrast, monocrotaline administration significantly decreased the expression of sarcolipin, SERCA2a, and phospholamban mRNAs in the RA than those in the LA. The two independent complementary experiments unequivocally demonstrated that mechanical stress down-regulates the transcription of the sarcolipin gene.