Key result
Benidipine at a subdepressor dose reversed upregulated ET-1 system expression to nondiabetic levels and hindered cardiomyocyte hypertrophy and cardiac perivascular fibrosis in diabetic rats.
Why the study?
Does benidipine ameliorate diabetic cardiac remodeling and normalize the endothelin system in a rat model of Type 2 diabetes?
Does benidipine ameliorate diabetic cardiac remodeling and normalize the endothelin system in a rat model of Type 2 diabetes?
A subdepressor dose of benidipine ameliorates diabetic cardiac remodeling in a rat model, potentially by normalizing the upregulated endothelin-1 system.
Hypothesis-generating for benidipine in diabetic cardiomyopathy; leaves open human translation from this rat model.
We investigated whether benidipine, a long-acting calcium channel blocker (CCB), can normalize cardiac expression profiles of the endothelin (ET)-1 system in insulin-resistant diabetes. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of human Type 2 diabetes, were treated for 12 wk with vehicle or benidipine (3 mg.kg(-1).day(-1)). OLETF rats exhibited a significant increase in ET-1 in plasma and left ventricular (LV) tissues compared with nondiabetic controls. Expression of prepro-ET-1, ET-converting enzyme, and ET(A) and ET(B) receptors in LV tissues was also significantly higher in OLETF rats. The two MAPKs, JNK and p38MAPK, both of which are activated by ET-1, were more abundantly expressed in OLETF rat LV tissues. All these alterations were reversed to nondiabetic levels when OLETF rats were treated with the subdepressor dose of benidipine. Furthermore, benidipine therapy resulted in hindering cardiomyocyte hypertrophy and cardiac perivascular fibrosis in OLETF rats. The beneficial actions of benidipine at the subdepressor dose on cardiac remodeling in insulin-resistant diabetes may involve normalization of the upregulated ET-1 system.
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Jesmin et al. (2005) studied Insulin-resistant diabetes. Benidipine vs. Vehicle was evaluated on Cardiac expression profiles of the endothelin (ET)-1 system. Benidipine at a subdepressor dose reversed upregulated ET-1 system expression to nondiabetic levels and hindered cardiomyocyte hypertrophy and cardiac perivascular fibrosis in diabetic rats.
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