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Reduction in central mitochondrial ROS improves cardiovagal baroreflex function independent of blood pressure in (mRen2)27 rats
Author(s) -
Nautiyal Manisha,
Shaltout Hossam A,
Chappell Mark C,
Diz Debra I
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.890.4
Subject(s) - reactive oxygen species , baroreflex , mitochondrial ros , medicine , endocrinology , mitochondrion , blood pressure , mean arterial pressure , chemistry , rostral ventrolateral medulla , heart rate , biology , biochemistry
Mitochondria‐derived reactive oxygen species (ROS) are potential therapeutic targets in hypertension. Transgenic (mRen2)27 rats overexpressing the murine Ren2 gene are hypertensive with impaired baroreflex sensitivity (BRS) for control of heart rate (HR). These animals also show elevated mitochondrial ROS in brain dorsal medulla, an important site for modulation of BRS. To determine whether central mitochondrial ROS influences mean arterial pressure (MAP) and BRS, the mitochondria‐targeted ROS scavenger Mito‐TEMPO (MT; 0.15 mg/day for 4 weeks) or artificial cerebrospinal fluid (aCSF) were infused ICV in 18 week old male (mRen2)27 rats. MT treatment failed to lower MAP but reduced HR [400 ± 23 vs. aCSF: 450 ± 7 bpm; p = 0.03; n = 4–7]. Lowering of HR was associated with increased vagal components of the spontaneous BRS [Sequence UP: 0.2 ± 0.2 vs. aCSF: −0.2 ± 0.1 ms/mm Hg; p = 0.03] and HR variability [SDRR: 7.6 ± 2 vs. aCSF: 3.3 ± 0.6 ms; p = 0.02]. Overall sympathovagal balance was reduced [LF RRI /HF RRI : −0.1 ± 0.1 vs. aCSF: 0.3 ± 0.1, p = 0.03]. Central scavenging of mitochondrial ROS improved BRS independent of MAP alterations in the (mRen2)27 rats. Since impaired BRS significantly associates with cardiovascular pathologies, both targeting of mitochondrial ROS and lowering of MAP may provide optimal therapeutic benefit.