AIM: To evaluate the role of angiotensin II receptor 1 antisense oligodexynucleotides (AT1R-AS-ODNs) on physi-ological and pathophysiological growth of cardiomyocytes from normotensive rats. METHODS: Cardiomyocyteswere transfected with AT1R-AS-ODNs (200 nmol/L) followed by treatment with or without angiotensin II (1 mol/L).In situ hybridization and Western blot were used for AT1R mRNA and protein detection, respectively. c-Jun N-terminal protein kinase (JNK) activity was characterized by immune complex kinase assay. c-Jun protein expres-sion was examined by immunocytochemistry. DNA content was detected by flow cytometric assay. Atrial natri-uretic factor (ANF) expression was identified by radioimmunoassay. RESULTS: Treatment with AT1R-AS-ODNsfor 24 h resulted in 51.2 % decrease in AT1R mRNA and 60.7 % in protein (P<0.05 vs control). However, the basallevel of JNK activity, c-Jun protein expression, and DNA content were not altered by AT1R-AS treatment in absenceof overactive hormonal system. After treatment with angiotensin II for 30 min, both p46JNK and p54JNK wererobustly activated. By 2 h, c-Jun protein expression was increased. By 24 h, angiotensin II caused a markedincrease both in G0/G1 and G2/M DNA content, and increased ANF expression by 1.8-fold. All these were inhibitedby AT1R-AS-ODNs pretreatment. In contrast, sense sequence was ineffective. CONCLUSION: Decrease ofAT1R expression by AS-ODNs did not interfere with normal growth, but protected cardiomyocytes from angio-tensin II-dependent pathophysiological growth. METHODS: Cardiomyocytes were transfected with AT1R-AS-ODNs (200 nmol / L) followed by treatment with or without angiotensin II (1 mol / L) .In situ hybridization and Western blot were used for AT1R mRNA and protein detection, respectively. c-Jun N-terminal protein kinase (JNK) activity was characterized by immune complex kinase assay . Atrial natriuretic factor (ANF) expression was identified by radioimmunoassay. RESULTS: Treatment with AT1R-AS-ODNs for 24 h resulted in 51.2 % decrease in AT1R mRNA and 60.7% in protein (P <0.05 vs control). However, the basallevel of JNK activity, c-Jun protein expression, and DNA content were not altered by AT1R-AS treatment in absence of overactive hor By 24 h, angiotensin II caused a marked increase in both G0 / G1 and G2 / M DNA. After 24 h, angiotensin II caused a marked increase in both G0 / G1 and G2 / M DNA content, and increased ANF expression by 1.8-fold. All these were inhibited by AT1R-AS-ODNs pretreatment. In contrast, sense sequence was ineffective. CONCLUSION: Decrease of AT1R expression by AS-ODNs did not interfere with normal growth, but protected cardiomyocytes from angio-tensin II-dependent pathophysiological growth.