The Effect And Mechanisms Of Chronic Intermittent Hypobaric Hypoxia On Vascular Functions In Rats

Objective: Many researches have showed that chronic intermittent hypobaric hypoxia (CIHH) conferred a protective effect on heart, including enhancing the resistance to heart against ischemia/reperfusion injury, relieving the decrease of cardiac function induced by ischemia/reperfusion and anti-arrhythmia, diminishing the myocardial infarction size and protecting against hypotension induced by acute hypoxia. However, the effect of CIHH on vascular functions remains not clear yet. So the aim of the present study was to observe the effects of CIHH on isolated thoracic aorta and pulmonary arteries rings in rat and investigate the underlying mechanisms.Methods: Sprague-Dawlay (SD) rats were randomly divided into 4 groups, control group (CON), 14 days CIHH treatment group (CIHH14), 28 days CIHH treatment group (CIHH28) and 42 days CIHH treatment group (CIHH42). CIHH rats were exposed to hypoxia in a hypobaric chamber simulating 3000 m altitude(PB=525mmHg, PO2=108.8mmHg), 5 hours daily for 14, 28 and 42 days, respectively. Control animals lived in the same environment as CIHH animals with free access to food and water excepting hypoxia. The body weight and general condition were recorded weekly. Animals were anaesthetized by pentobarbital sodium (50 mg/kg i.p.). The thorax was opened in order to excise the pulmonary artery and thoracic aorta, then observe the diastolic and contractive activity of the artery rings using organ bath technique,meanwhile,examine the activity of NOS and concentration of NO.Results: (1) Relaxation to acetylcholine (ACh) and contraction to KCl were similar in CIHH and normoxic (CON) rats. (2) Noradrenaline (NE) induced contraction in CIHH group was obviously increased than CON group in thoracic aorta (P<0.05), but there showed no difference in pulmonary artery. However, the contraction to Angiotoninâ…¡(ANGâ…¡) was impaired in CIHH group than CON group (P<0.05). (3) The increased contraction to NE could be blocked by cyclooxygenase inhibitor indomethacin (Indo), ICa-L blocker verapamil (Ver) and free radical scavenger Tempol; in contrast, the decreased contraction to ANGâ…¡could be reversed by KATP blocker Glibenclamide (Gli) and free radical scavenger Tempol. (4) The activity of NOS and concentration of NO were obviously decreased in CIHH group than CON group (P<0.05).Conclusion: The data demonstrated that CIHH augmented NE induced vasoconstriction in thoracic aorta rings which was related with the opening of ICa-L, decrease of NOS activity and NO production, as well as the increased production of cyclooxygenase and free radical. However, CIHH attenuated the contraction response of thoracic aorta rings to ANGâ…¡, which was related with the opening of KATP, and the increased production of free radical.