Myocardial ischemia and reperfusion(I/R) is a common problem in clinic and there is no satisfactory method for prevention or treatment of I/R injury so far.Chronic intermittent hypobaric hypoxia(CIHH),similar to the concept of ischemia preconditioning(IPC)or altitude hypoxia adaptation(AHA),has been recognized to confer a protective effect on heart against I/R injury with a longer protective effect than IPC and a less adverse effect than AHA.It has been proved that CIHH increases myocardial tolerance to ischemia or hypoxia,reserving cardiac function and preventing arrhythmia during I/R.Multiple mechanisms or pathway underlying the cardiac protection of CIHH have been proposed,such as induction of heatshock protein,enhancement of myocardial antioxidation capacity,increase of coronary flow and myocardial capillary angiogenesis,activation of adenosine triphosphate(ATP)-sensitive potassium channels,inhibition of mitochondrial permeability transition pores,and activation of protein kinase C(PKC) and induced nitric oxide synthase(iNOS).In addition,CIHH has been found having many beneficial effects on the body,such as promotion of health,increase of oxygen utilization,and prevention or treatment for some diseases.The beneficial effects of CIHH and potential mechanisms are reviewed mainly based on the researches performed by our group.
Chronic intermittent hypobaric hypoxia(CIHH)is known to have an anti-hypertensive effect, which might be related to modulation of the baroreflex in rats with renal vascular hypertension(RVH). In this study, RVH was induced by the 2-kidney-1-clip method(2 K1 C) in adult male Sprague-Dawley rats. The rats were then treated with hypobaric hypoxia simulating 5000 m altitude for 6 h/day for 28 days. The arterial blood pressure(ABP), heart rate(HR), and renal sympathetic nerve activity(RSNA) were measured before and after microinjection of L-arginine into the nucleus tractus solitarii(NTS) in anesthetized rats.Evoked excitatory postsynaptic currents(eEPSCs) and spontaneous EPSCs(sEPSCs) were recorded in anterogradely-labeled NTS neurons receiving baroreceptor afferents. We measured the protein expression of neuronal nitric oxide synthase(nNOS) and endothelial NOS(eNOS) in the NTS. The results showed that the ABP in RVH rats was significantly lower after CIHH treatment. The inhibition of ABP, HR, and RSNA induced by L-arginine was less in RVH rats than in sham rats, and greater in the CIHHtreated RVH rats than the untreated RVH rats. The eEPSC amplitude in NTS neurons receiving baroreceptor afferents was lower in the RVH rats than in the sham rats and recovered after CIHH. The protein expression of nNOS and e NOS in the NTS was lower in the RVH rats than in the sham rats and this decrease was reversed by CIHH. In short, CIHH treatment decreases ABP in RVH rats via upregulating NOS expression in the NTS.
Na LiYue GuanYan-Ming TianHui-Jie MaXiangjian ZhangYi ZhangSheng Wang
