Role of components of the phagocytic NADPH oxidase in oxygen sensing

K. A. Sanders, K. M. Sundar, L. He, B. Dinger, S. Fidone, J. R. Hoidal
2002 Journal of applied physiology  
of components of the phagocytic NADPH oxidase in oxygen sensing. It has been hypothesized that O 2 sensing in type I cells of the carotid body and erythropoietin (EPO)-producing cells of the kidney involves protein components identical to the NADPH oxidase system responsible for the respiratory burst of phagocytes. In the present study, we evaluated O 2 sensing in mice with null mutant genotypes for two components of the phagocytic oxidase. Whole body plethysmography was used to study
more » ... ized, unrestrained mice. When exposed to an acute hypoxic stimulus, gp91 phoxnull mutant and wild-type mice increased their minute ventilation by similar amounts. In contrast, p47 phox -null mutant mice demonstrated increases in minute ventilation in response to hypoxia that exceeded that of their wild-type counterparts: 98.0 Ϯ 18.0 vs. 20.0 Ϯ 13.0% (n ϭ 11, P ϭ 0.003). In vitro recordings of carotid sinus nerve (CSN) activity demonstrated that resting (basal) neural activity was marginally elevated in p47 phox -null mutant mice. With hypoxic challenge, mean CSN discharge was 1.5-fold greater in p47 phoxnull mutant than in wild-type mice: 109.61 Ϯ 13.29 vs. 72.54 Ϯ 7.65 impulses/s (n ϭ 8 and 7, respectively, P ϭ 0.026). Consequently, the hypoxia-evoked CSN discharge (stimulus-basal) was ϳ58% larger in p47 phox -null mutant mice. Quantities of EPO mRNA in kidney were similar in gp91 phox -and p47 phox -null mutant mice and their respective wild-type controls exposed to hypobaric hypoxia for 72 h. These findings confirm the previous observation that absence of the gp91 phox component of the phagocytic NADPH oxidase does not alter the O 2-sensing mechanism of the carotid body. However, absence of the p47 phox component significantly potentiates ventilatory and chemoreceptor responses to hypoxia. O 2 sensing in EPO-producing cells of the kidney appears to be independent of the gp91 phox and p47 phox components of the phagocytic NADPH oxidase. carotid body; erythropoietin; hypoxia Address for reprint requests and other correspondence: J. R. Hoidal, Pulmonary Div.,
doi:10.1152/japplphysiol.00564.2001 pmid:12235036 fatcat:3l2lp3md75ffzlyzpod6452ixe