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- Title
Role of NAD(P)H oxidase in the regulation of cardiac L-type Ca<sup>2+</sup> channel function during acute hypoxia
- Authors
Hool, Livia C.; Di Maria, Carla A.; Viola, Helena M.; Arthur, Peter G.
- Abstract
Abstract: Objective: The role of NAD(P)H oxidase in regulating cellular production of reactive oxygen species (ROS) and the L-type Ca2+ channel during acute hypoxia was examined in adult ventricular myocytes from guinea pig. Methods: The fluorescent indicator dihydroethidium (DHE) was used to detect superoxide and the response of the L-type Ca2+ channel to β-adrenergic receptor stimulation was used as a functional reporter since hypoxia increases the sensitivity of the L-type Ca2+ channel (ICa-L) to isoproterenol (Iso). Results: Hypoxia caused a 41.2±5.2% decrease in the rate of the DHE signal (n =21; p &#60;0.01). Of the classical NAD(P)H oxidase inhibitors, DPI but not apocynin mimicked the effect of hypoxia on the sensitivity of ICa-L to Iso. However, the potent NAD(P)H oxidase agonist angiotensin II had no effect on cellular superoxide or the sensitivity of ICa-L to Iso. Although DPI inhibits NAD(P)H oxidase, it also decreased superoxide in isolated mitochondria in a concentration-dependent manner. Partial inhibition of mitochondrial function with nanomolar concentrations of FCCP or myxothiazol mimicked the effect of hypoxia on cellular superoxide and the sensitivity of ICa-L to Iso. In addition, hypoxia caused a 69.3±0.8% decrease in superoxide in isolated mitochondria (n =4; p &#60;0.01), providing direct evidence for a role for the mitochondria. Conclusions: Our data suggest that mitochondria appear to be involved in oxygen sensing, regulation of cellular ROS, and the function of ICa-L during acute hypoxia in cardiac myocytes and NAD(P)H oxidase does not appear to contribute substantially.
- Subjects
OXIDASES; MUSCLE cells; HYPOXEMIA; GUINEA pigs
- Publication
Cardiovascular Research, 2005, Vol 67, Issue 4, p624
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1016/j.cardiores.2005.04.025