Effect of mechanical stretch on rat neonatal cardiomyocyte somatostatin receptor subtype 1 expression

Abstract

Somatostatin receptors (SSTRs) have been proven to be involved in cardioprotection, but the effects of mechanical stress on their expression remain to be elucidated. To investigate whether mechanical stretch is associated with increased expression of the SSTR in cardiomyocytes and if the phenomenon is mediated via an angiotensin II signaling pathway. Using a well established cyclic mechanical stretch model exerting strain on primary cultured neonatal Wistar rat cardiomyocytes, we studied the expression of major SSTRs of cardiomyocyte under such stress. Western blot and immunoprecipitation were used to demonstrate the related changes. The role of endogenous angiotensin II and the effects of AT-1 receptor blockade were studied by pre-administration of losartan. Northern and western blotting revealed progressive increase of SSTR-1 mRNA and protein expression as the duration of stretch increased up to 48 hours. The maximal increases of SSTR-1 mRNA and protein were observed at 24 hours. The mechanical stretch significantly increased the angiotensin II in cardiomyocytes concomitantly. Losartan and PD98059 had a significant inhibitory effect on the expression of SSTR-1, indicating the angiotensin II and p42/p44 MAP kinases-related pathways were involved in the expression of SSTR-1 under mechanical stress. By contrast, tyrosine kinases, protein kinase A, protein kinase C, JAK-2, JNK and phosphoinositol-3-kinases had no effect. This study demonstrated that accentuating the expression of SSTR-1mechanical stretch is angiontensin II and p42/p44 MAP kinases-dependent.