Effect Of NADPH Oxidase Inhibitor-Apocynin On The Expression Of Hypoxia Inducible Factor1α And Endothelin-1in Rats Carotid Body Exposed Chronic Intermittent Hypoxia

Obejective: To observe the effect of Nicotinamide Adenine Dinucleotide Phosphate（NADPH） oxidase inhibitor-Apocynin on the expression of hypoxia-induciblefactor-1α(HIF-1α), endothelin-1(ET-1) in carotid body, and systolic blood pressure underchronic intermittent hypoxia (CIH) condition, and investigate the mechanism of OSAHS-induced hypertension.Methods: To mimic the intermittent hypoxia of obstructive sleep apnea-hypopneasyndrome (OSAHS) in humans, and establish a chronic intermittent hypoxia (CIH) animalmodel in rats.30healthy eight-week old Sprague-Dawley male rats were randomly dividedinto three groups (n=10in each group): a sham group, a CIH group, a apocynin-treated CIHgroup. The CIH group and the apocynin-treated CIH group were placed in an animalchamber exposed to chronic intermittent hypoxia for8hours per day (from9AM to5PM).The ambient oxygen concentration ranged from6%-21%and110second of eachcycle. The rats in sham group were placed in the same chamber without chronicintermittent hypoxia. For apocynin-treated CIH rats, apocynin was intragastric administered(3mg/kg/day) throughout intermittent hypoxia exposure. And0.9﹪saline for the shamgroup and CIH group. The experimental lasted for4weeks. Tail artery systolic bloodpressure was measured by tail-cuff method. The measurement of arteria caudilis blood pressure of rats was conducted according to the instruction of the measurement meter ofarteria caudilis blood pressure of rats.Real-time fluorescence quantitative polymerase chainreaction (RT-PCR)were used to examine mRNA expression of HIF-1α and ET-1in thecarotid body and HIF-1α protein expression with western blotting. The level of MDA andSOD were detected by colorimetric method. In addition, the circulating ET-1and HIF-1α inthe serum were measured with enzyme-linked immune sorbent assay.Results Apocynin treatment prevented CIH-induced hypertension as well as CIH-inducedincrease in SOD activity. In untreated animals, CIH exposure was associateted withincreasing of MDA levels and circulating ET-1levels in comparison to sham animals, andapocynin-treated animals exposed to CIH showed reduction in MDA and circulating ET-1levels. Increase in carotid body HIF-1α and protein expression、 circulating HIF-1α andET-1mRNA were observed in CIH-exposed animals, there were no statistic different ofHIF-1α mRNA expression between CIH group and apocynin treatment group. Treatmentwith apocynin significantly lessened the ET-1mRNA and HIF-1α protein expression andcirculating HIF-1α level in CIH-exposed animals.Conclusion: These results indicate that apocynin alleviated CIH-induced hypertension,vasoconstrictor ET-1level and oxidative stress through the effect of inhibiting NADPHoxidase. HIF-1α/ET-1system signal pathway may be closely associated with oxidativeprocesses in CIH rat, especially that depended on NADPH oxidase. Inhibiting of NADPHoxidase activity may be hopefully serves as a useful strategy for prevention and treatmentof OSAHS-induced hypertension...