March 9, 1998Circulation Research
Role of Ion Channels and Exchangers in Mechanical Stretch–Induced Cardiomyocyte Hypertrophy
Key result
The Na+-H+ exchanger inhibitor HOE 694 attenuated stretch-induced activation of Raf-1 kinase and MAP kinases by approximately 50% and 60%, respectively, in neonatal rat cardiomyocytes.
Population
Neonatal rat cardiomyocytes cultured on expandable silicone dishes
Comparison
Pretreatment with specific inhibitors of… vs Mechanical stretch without specific inhibitors
Design
Preclinical
Authors
Discussion
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Implication
Implicates NHE in stretch-induced cardiomyocyte signaling; hypothesis-generating for in vivo hypertrophy and remodeling.
Key Points
- This research aims to explore if mechanosensitive ion channels and exchangers contribute to cardiomyocyte hypertrophy caused by mechanical stretching.
- Cultured neonatal rat cardiomyocytes on expandable silicone dishes were stretched after specific inhibitor pretreatment.
- Inhibitors used included gadolinium, streptomycin, glibenclamide, CsCl, and HOE 694 targeting various ion channels and exchangers.
- Activation of Raf-1 kinase and MAP kinases was assessed following mechanical stretch.
- HOE 694 significantly reduced stretch-induced activation of Raf-1 kinase by approximately 50% and MAP kinases by 60%.
- Increased protein incorporation was also attenuated by HOE 694 during stretch.
- Other inhibitors did not affect the activation of MAP kinases due to mechanical stretch.
Structured PICO
P
Population
Neonatal rat cardiomyocytes cultured on expandable silicone dishes to study stretch-induced hypertrophic responses.
I
Intervention
Pretreatment with specific inhibitors of stretch-sensitive cation channels (gadolinium and streptomycin), ATP-sensitive K+ channels (glibenclamide), hyperpolarization-activated inward channels (CsCl), or Na+-H+ exchanger (HOE 694) prior to mechanical stretch
C
Comparator
Mechanical stretch without specific inhibitors (implied)
O
Outcome
Activation of Raf-1 kinase and MAP kinases, and phenylalanine incorporation into proteinssurrogate
The Na+-H+ exchanger plays a critical role in mechanical stress-induced cardiomyocyte hypertrophy, highlighting a potential molecular mechanism in cardiac remodeling.
Cite This Study
Yamazaki et al. (1998) studied Cardiomyocyte hypertrophy. Na+-H+ exchanger inhibitor (HOE 694) was evaluated on Stretch-induced activation of Raf-1 kinase and MAP kinases. The Na+-H+ exchanger inhibitor HOE 694 attenuated stretch-induced activation of Raf-1 kinase and MAP kinases by approximately 50% and 60%, respectively, in neonatal rat cardiomyocytes.