Oxidative impairment of mitochondrial electron transport chain complexes in rostral ventrolateral medulla contributes to neurogenic hypertension

Samuel H.H. Chan, Kay L.H. Wu, Alice Y.W. Chang, Ming Hon Tai, Julie Y.H. Chan

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97 Citations (Scopus)

Abstract

The role for mitochondrial electron transport chain (ETC) in neurogenic hypertension is unidentified. We evaluated the hypothesis that feedforward depression of mitochondrial ETC functions by superoxide anion (O 2.-) and hydrogen peroxide (H2O2) in rostral ventrolateral medulla (RVLM), a brain stem site that maintains sympathetic vasomotor tone and contributes to oxidative stress and neural mechanism of hypertension. Compared with normotensive Wistar-Kyoto rats, spontaneously hypertensive rats exhibited mitochondrial ETC dysfunctions in RVLM in the forms of depressed complex I or III activity and reduced electron coupling capacity between complexes I and III or II and III. Microinjection of coenzyme Q10 into RVLM of spontaneously hypertensive rats reversed the depressed ETC activity and augmented O2.- production and hypertensive phenotypes. This mobile electron carrier also antagonized the elevated H2O2 in RVLM and vasopressor responses to complex I (rotenone) or III (antimycin A) inhibitor in Wistar-Kyoto or prehypertensive rats. Intracerebroventricular infusion of angiotensin II promoted mitochondrial ETC dysfunctions in Wistar-Kyoto rats, and coenzyme Q10 or gene knockdown of the p22phox subunit of NADPH oxidase antagonized the resultant elevation of H2O2 in RVLM. Overexpression of superoxide dismutase or catalase in RVLM of spontaneously hypertensive rats by gene transfer reversed mitochondrial dysfunctions and blunted the augmented O2.- and H2O2 in RVLM. We conclude that O2.-- and H2O2-dependent feedforward impairment of mitochondrial ETC complexes because of predisposed downregulation of superoxide dismutase or catalase and a cross-talk between NADPH oxidase-derived O2.- and ETC enzymes contribute to chronic oxidative stress in the RVLM of spontaneously hypertensive rats, leading to augmented sympathetic vasomotor tone and hypertension.

Original languageEnglish
Pages (from-to)217-227
Number of pages11
JournalHypertension
Volume53
Issue number2
DOIs
Publication statusPublished - 2009 Feb

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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