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- Title
Direct effects of the angiotensin-converting enzyme inhibitor ramiprilat on adult rat ventricular cardiomyocytes.
- Authors
Helmig, S.; Schuckenböhmer, P.; Heger, J.; Euler, G.; Piper, H. M.; Schlüter, K.-D.
- Abstract
Aim: Angiotensin-converting enzyme (ACE) inhibitors like ramiprilat bind to ACE expressed on the cell surface of endothelial cells and induce cell-specific signalling including the activation of activator protein (AP)-1. The present study addressed the question whether ramiprilat exerts a similar effect on adult ventricular cardiomyocytes, i.e. activates the AP-1 or modifies contractile performance. It was further aimed to decide whether such effects depend on bradykinin receptors or whether they are directly mediated via ACE. Methods: Adult rat ventricular cardiomyocytes were isolated and cultured. mRNA expression of ACE was investigated by RT-PCR, AP-1 activation by gel mobility shift assays, and cardiac contractile performance by electrical pacing of isolated cells and analysis of cell shortening via a line-camera. Results: Cardiomyocytes stably express ACE. Ramiprilat increased maximal contraction velocity and shortened the time-to-peak of contraction. In contrast to effects evoked by bradykinin, such effects caused by ramiprilat were not attenuated by HOE 140, a bradykinin-receptor antagonist. These effects were also not attenuated in the presence ofl-nitro-arginine, used to mimic bradykinin-dependent signalling. In cardiomyocytes, bradykinin but not ramiprilat activated AP-1. Ramiprilat activates AP-1 in endothelial cells that are known to respond to ramiprilat in this way. Conclusion: Ramiprilat exerts direct, bradykinin-receptor independent effects on cardiomyocytes that improve cellular function without a corresponding effect on AP-1 activation or induction of AP-1 dependent effects. This newly described effect of ramiprilat may contribute to the protective effects seen by application of ACE inhibitors.
- Subjects
ACE inhibitors; LABORATORY rats; HEART cells; BRADYKININ; CARDIAC contraction; MESSENGER RNA
- Publication
Acta Physiologica, 2007, Vol 191, Issue 4, p267
- ISSN
1748-1708
- Publication type
Article
- DOI
10.1111/j.1748-1716.2007.01738.x