Vitamin E deficiency accelerates nitrate tolerance via a decrease in cardiac P450 expression and increased oxidative stress

Free Radical Biology & Medicine
Yukiko MinamiyamaShigeru Okada

Abstract

Organic nitrates, such as nitroglycerin (NTG), have been used to relieve the symptoms of angina pectoris. However, their biochemical mechanisms of action, particularly in relation to the development of tolerance, are incompletely defined. It has been reported that supplemental antioxidants such as vitamin E attenuate the development of nitrate tolerance. Therefore, we examined the role of vitamin E in the regulation of nitrate tolerance. Continuous NTG infusion induced nitrate tolerance in rats after 48 h, and vitamin E concentrations decreased in a time-dependent manner in tissues and plasma. Vitamin E supplementation (0.5 g/kg diet) maintained higher concentrations of vitamin E during NTG infusion. The onset and extent of the tolerance, estimated by the decrease in blood pressure following NTG bolus injection during the infusion of NTG, were accentuated in the vitamin E-deficient group. Vitamin E supplementation inhibited nitrate tolerance 48 h after NTG infusion. Cardiac P450 expression (CYP1A2) assessed by immunoblotting, markedly decreased 48 h after NTG administration in control rats. The supplementation of vitamin E significantly attenuated the decrease in P450. Treatment of NTG enhanced vascular superoxide production (L...Continue Reading

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Citations

Jun 25, 2008·The British Journal of Nutrition·Siegfried KnasmüllerKarl-Heinz Wagner
Feb 7, 2012·Antioxidants & Redox Signaling·Nicoletta CastiglioneFrancesca Cutruzzolà
Jun 25, 2010·Circulation Journal : Official Journal of the Japanese Circulation Society·Atsushi NakahiraShigefumi Suehiro
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Aug 17, 2011·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Xin WangChun-Xu Hai
Oct 28, 2006·The Journal of Pharmacology and Experimental Therapeutics·Yukiko MinamiyamaShigeru Okada
Mar 11, 2010·American Journal of Physiology. Endocrinology and Metabolism·Yukiko MinamiyamaShigeru Okada
Jan 21, 2009·The Biochemical Journal·Catherine N HallJohn Garthwaite
Feb 28, 2021·Signal Transduction and Targeted Therapy·Bei WangDao Wen Wang
Apr 30, 2008·Journal of Medicinal Chemistry·Loris Grossi

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