Abnormalities in blood pressure, heart rate and baroreflex sensitivity in dual oxidase 2 (DUOX2) knockout mice.

Abstract

DUOX2 participates in thyroid hormone synthesis and possibly cell signaling and host defense by producing reactive oxygen species in thyroid gland, exocrine glands and the gastrointestinal and respiratory tracts. The role of DUOX2 in cardiovascular (CV) physiology is unexplored. We hypothesized that DUOX2 deficient mice (DUOX2−/−) would have altered CV and baroreflex function compared to controls. 24hr heart rate (HR), blood pressure (BP) and locomotor activity (LA) were determined by telemetry, and baroreflex sensitivity (BRS) was calculated from spontaneous reciprocal fluctuations in BP and HR using the sequence method. Compared to controls (n=5), DUOX2−/−mice (n=4) exhibited hypotension (91±3 vs 100±2 mmHg, p<0.05) and bradycardia (475±8 vs 569±17 bpm, p<0.05). Analysis of CV circadian patterns revealed that these decreases in BP and HR in DUOX2−/− were even more dramatically pronounced during the resting (light) period (BP: 79±2 vs 97±2 mmHg; HR: 411±17 vs 544±20 bpm, p<0.05). Importantly, LA was not different in DUOX2−/−during this time. BRS was augmented in DUOX2−/− vs controls (3.21±0.63 vs 1.50±0.08 ms/mmHg, n=4 each, p<0.05), but only during periods of LA. These findings suggest that DUOX2 plays a key role in the basal regulation of CV and baroreflex function. Whether this is related to thyroid hormone synthesis or other as yet unidentified functions of DUOX2 in the CV system is under investigation.