期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 174, 期 20, 页码 3640-3653出版社
WILEY
DOI: 10.1111/bph.13967
关键词
-
资金
- Austrian Science Fund (FWF) [P24946]
- Austrian National Bank [16435]
- Austrian Science Fund (FWF) [P24946] Funding Source: Austrian Science Fund (FWF)
Background and Purpose The antioxidant 5-hydroxymethylfurfural (5-HMF) exerts documented beneficial effects in several experimental pathologies and is currently tested as an antisickling drug in clinical trials. In the present study, we examined the cardiovascular effects of 5-HMF and elucidated the mode of action of the drug. Experimental Approach The cardiovascular effects of 5-HMF were studied with pre-contracted porcine coronary arteries and rat isolated normoxic-perfused hearts. Isolated hearts subjected to ischaemia/reperfusion (I/R) injury were used to test for potential cardioprotective effects of the drug. The effects of 5-HMF on action potential and L-type Ca2+ current (I-Ca,I-L) were studied by patch-clamping guinea pig isolated ventricular cardiomyocytes. Key Results 5-HMF relaxed coronary arteries in a concentration-dependent manner and exerted negative inotropic, lusitropic and chronotropic effects in rat isolated perfused hearts. On the other hand, 5-HMF improved recovery of inotropic and lusitropic parameters in isolated hearts subjected to I/R. Patch clamp experiments revealed that 5-HMF inhibits L-type Ca2+ channels. Reduced I-Ca,I-L density, shift of I-Ca,I-L steady-state inactivation curves toward negative membrane potentials and slower recovery of I-Ca,I-L from inactivation in response to 5-HMF accounted for the observed cardiovascular effects. Conclusions and Implications Our data revealed a cardioprotective effect of 5-HMF in I/R that is mediated by inhibition of L-type Ca2+ channels. Thus, 5-HMF is suggested as a beneficial additive to cardioplegic solutions, but adverse effects and contraindications of Ca2+ channel blockers have to be considered in therapeutic application of the drug.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据