Intermittent hypoxia conditioning prevents endothelial dysfunction and improves nitric oxide storage in spontaneously...

Although intermittent hypoxia is often associated with hypertension, experimental and clinical studies have demonstrated definite antihypertensive effects of some intermittent hypoxia conditioning (IHC) regimens. Mechanisms of this antihypertensive response are unknown. Endothelial dysfunction related to disturbed synthesis and/or reduced availability of nitric oxide (NO) has been linked to hypertension. Thus, experiments were conducted to determine if IHC can improve endothelium-dependent relaxation and formation of releasable vascular NO stores of young (4-8-week-old) spontaneously hypertensive rats (SHR). Rats were subjected to either IHC (9.5-10% O(2), 5-10 min, 5-8 times per day, 20 d) or to sham conditioning. Endothelium-dependent relaxation to acetylcholine was measured in norepinephrine-precontracted, isolated aortic rings, and the size of NO stores was evaluated by percent relaxation to N-acetylcysteine (NAC), which releases stored NO. The capacity of aortic rings for NO storage was evaluated by the relaxation to NAC after prior incubation with an NO donor. IHC significantly suppressed the development of hypertension in young SHR. Endothelial function decreased from 54.7 ± 4.6% to 28.1 ± 6.4% relaxation to acetylcholine after 20 d of sham IHC, whereas endothelial function was sustained (60.3 ± 6.0% relaxation) in IHC rats. IHC also induced formation of available NO stores and enhanced the capacity of aortic rings to store NO. Therefore, the antihypertensive effect of IHC in young SHR is associated with prevention of endothelial dysfunction and with increased accumulation of NO stores in vascular walls.