Homocysteine ameliorates the endothelium-independent hypoxic vasoconstriction via the suppression of phosphatidylinositol 3-kinase/Akt pathway in porcine coronary arteries.

OBJECTIVE:Endothelium-independent coronary vasoconstriction induced by continuous hypoxia contributes to the development of ischemic heart diseases. Acute elevation of homocysteine (Hcy) has a potent of vasodilation. The present study aims to investigate the role of Hcy in endothelium-independent hypoxic coronary vasoconstriction and its underlying mechanisms. METHODS AND RESULTS:Vessel tension of isolated porcine coronary arteries was measured by organ chamber study and the protein expression were detected by western blot. A sustained contraction of porcine coronary artery was induced when exposed to prolonged hypoxia for more than 15 min, which was significantly reduced by Hcy in a dose-dependent manner but not affected by cysteine or N-acetyl-l-cysteine. Phosphorylated myosin light chain (MLC-p) at Ser19 was decreased when exposure to hypoxia for 15 min, and could be reversed by prolonged hypoxia for 30 and 60 min. The recovery of MLC-p at Ser19 by hypoxia for more than 30 min could be abolished by Hcy. The protein levels of phosphorylated Akt at Ser473 and phosphorylated P85 at Tyr508 were decreased by Hcy in normoxia, and were also reduced exposure to hypoxia for 15 min and then augmented by prolonged hypoxia for more than 30 min, which could be prevented by Hcy. The protein level of P110α was not affected by Hcy or prolonged hypoxia. CONCLUSIONS:This study demonstrates that Hcy can ameliorate the endothelium-independent hypoxic coronary vasoconstriction, in which the inhibition of PI3K/Akt signaling pathway may be involved.

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