Question: 

Intercellular communication is an important feature of organization within many kinds of tissue. Gap junction channels form the basis of direct intercellular communication. In the heart the predominant gap junction protein is connexin43 (Cx43). Increased Cx43-expression has been identified in cardiac hypertrophy and may contribute to arrhythmia. Since angiotensin-II plays an important role in cardiac remodelling, we wanted to elucidate whether sub-chronic angiotensin-receptor (AT-R) stimulation may affect Cx43-expression and whether this might be modulated by mechanical stretch.

Methods: 

Neonatal rat cardiomyocytes cultured on gelatine coated FlexCell cell culture plates were exposed to pulsatile stretch (110% of resting length, 1Hz) for 24 hours without stimulation of AT-R or in presence of 0.1mM angiotensin-II. Moreover, in a second series of experiments inhibitors of AT-R were used in combination with angiotensin-II and stretch (for AT1-R: losartan 0.1mM, for AT2-R PD123177 0.1mM). Thereafter, Cx43-protein and mRNA expression was examined. Moreover, phosphorylated ERK1/2 (P-ERK1/2) and the small G-proteins were investigated.

Results: 

Exposure to pulsatile stretch or angiotensin-II led to a significant increase in Cx43-protein and mRNA expression by about 50%. Combined stimulation of the cardiomyocytes by stretch and angiotensin-II led to a significant further enhancement of Cx43 on protein and mRNA level. Both, the angiotensin-II and stretch signals were significantly inhibited by losartan but not by PD123177. ERK1/2 phosphorylation was significant after angiotensin-II stimulation or stretch application and could also be inhibited by losartan. Rho and Rac were significantly elevated by about 30% by angiotensin-II but not by stretch.

Conclusions: 

Thus, angiotensin-II and stretch increase Cx43 expression on protein and mRNA level probably through phosphorylation of ERK1/2 via AT1-R. The small G-proteins seem to be involved in the angiotensin-II but not in the stretch signalling.