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.

Earlier we reported that intermittent hypoxia conditioning (IHC) slows development of hypertension in young spontaneously hypertensive rats (SHR) and stimulates nitric oxide (NO) synthesis. Now we have compared basal and stimulated NO production in IHC and sham conditioned, 4–5 week old SHR. IHC protocol: 20 days, 5 to 8 cycles of 9.5–10% O2, each 5 to 10 min, separated by 4 min normoxia. Sham protocol: same regimen but no change in inspired O2. The 20 day rise of systolic BP of IHC rats was less than in sham rats (from 131±2 mmHg to 162±2 mmHg vs 202±3 mmHg in sham rats, P<0.001). Basal NO production was evaluated by the contractile response to norepinephrine (NE, 10− 8M) of isolated aortic rings in the presence and absence of L‐NAME (10−3 M), an NO synthase inhibitor. After L‐NAME, NE‐induced contraction increased more (P<0.05) in IHC rats (66±16%) than in sham rats (35±3%). Endothelium‐dependent relaxation (EDR) was evaluated by the response to acetylcholine of NE‐precontracted rings. In 8‐week old IHC rats, EDR was not impaired and did not differ from that of 4–5 week old SHR (60±6%). EDR was impaired in 8‐week old sham‐IHC rats compared to 4–5 week old rats (28±6 vs 55±5%, P<0.002). Therefore, the antihypertensive effect of IHC is associated with improvement of both basal and stimulated NO production. These effects may indicate an important role of NO in the antihypertensive action of IHC. (Support: UNTHSC Cardiovasc. Res. Inst.)

Hypobaric intermittent hypoxia (IH) has been shown to have anti‐hypertensive action, and IH therapy is used clinically to treat hypertensive patients in Eastern European countries. The present study evaluated the effects of normobaric IH on the progression of hypertension in spontaneously hypertensive rats (SHR). Four‐five week old SHR were subjected to either IH (n=15) or to sham IH (n=10). IH rats were exposed for 20 consecutive days to intermittent hypoxia (5 to 8 cycles of 9.5–10 % O2, each 5 to 10 min, separated by 4 min normoxia).Sham rats were subjected to the same regimen but with no change in inspired O2. Systolic blood pressure (SBP) was measured in all the animals using the tail cuff method (IITC Life Science). Pre‐treatment SBP (mean ± SEM) of IH rats (131 ± 2 mmHg) and sham rats (132 ± 3 mmHg) were similar. After 20 days of IH, SBP of IH rats (162 ± 2 mmHg) was significantly lower (P < 0.001) than that of sham rats (202 ± 3 mmHg). IH associated with sleep apnea is known to cause hypertension. However, the IH regimen of this study, which differs from the IH of sleep apnea, clearly blunted the development of hypertension in young SHR. The anti‐hypertensive mechanism of this regimen of IH merits further investigation.