Changes of blood pressure and expression of NADPH oxidase in carotid body in rats exposed to intermittent hypoxia

Abstract

Chronic intermittent hypoxia (CIH) occurs in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and has adverse effects on multiple physiological functions. Previous studies have shown that reflexes arising from carotid bodies mediate CIH evoked circulation-respiratory responses, and reactive oxygen species (ROS) play important roles in eliciting systemic responses to CIH. But very little is known about the molecular mechanisms underlying CIH. NADPH oxidase is the most important sources of ROS. In the present study we examined changes of blood pressure and expression of NADPH oxidase in carotid body in rats exposed to intermittent hypoxia. Thirty healthy male SD rats were randomly divided into 3 groups, a CIH group, a chronic continuous hypoxia group and a control group. The systolic blood pressure (SBP) was measured with tail-cuff method. RT-PCR was used to examine mRNA expressions of NADPH oxidase subunit gp91phox, p22phox, p47phox. Immunohistochemistry and semiquantitative analysis of NADPH oxidase subunits p22phox were done in the carotid body sections of all rats. Compared with normal group [(124 ± 7) mm Hg, 1 mm Hg = 0.133 kPa] and chronic continuous hypoxia group[(129 ± 9) mm Hg], the SBP in CIH group [(145 ± 11) mm Hg] was significantly higher(F = 19.895, P < 0.01), and the expression of NADPH oxidase subunits gp91phox, p22phox, p47phox mRNA in CIH group (2.82 ± 0.51, 2.74 ± 0.45, 2.88 ± 0.47, respectively) were significantly higher than those in chronic continuous hypoxia group (2.35 ± 0.42, 2.25 ± 0.38, 2.41 ± 0.43, respectively) and normal group (2.23 ± 0.35, 2.16 ± 0.30, 2.30 ± 0.36, respectively) (F = 5.794, 6.854, 7.163, respectively, P < 0.01). The Immunohistochemistry and semiquantitative analysis showed that the expression of NADPH oxidase subunit p22phox in the carotid body in CIH group (99 ± 12) were more than those in chronic continuous hypoxia and control groups (38 ± 7 and 34 ± 8, P < 0.05). CIH upregulates the expression of NADPH oxidase in rat carotid body and elevates the rat SBP. These results indicate that NADPH oxidase up-expression is closely associated with OSAHS patients with hypertension.