Role of nitric oxide in adaptation to hypoxia and adaptive defense - Manukhina et al. (2000)
Adaptation to hypoxia increases NO production and storage
Simultaneously, adaptation to hypoxia protects against NO over- and under-production
The Breathing Diabetic Summary
A paper we recently reviewed found that the production and storage of nitric oxide (NO) increases significantly during adaptation to hypoxia. This paper wanted to see what would happen during adaptation to hypoxia in disorders of either NO over-production or NO deficiency.
Three different types of Wistar rats were studied. The first was a model of NO overproduction (NO+), the second a model of NO deficiency (NO-), and the third a control group.
The same protocol from their previous work was used for adaptation to hypoxia: They gradually adapted mice to hypoxia in an altitude chamber simulating ~5000 m (hypobaric hypoxia). The mice completed 40 sessions. They started at 10 min the first session, then 20 min the second session, and so on until they reached 5 hours of simulated altitude per session.
After the full acclimation, the control mice nearly doubled their NO metabolites. Their NO storage had significantly increased as well. These results indicated that NO production and storage increased due to adaptation to hypoxia.
These adaptations were beneficial for the other mice studied. The NO+ mice that were not acclimated to hypoxia showed a drop in blood pressure of about 36 mm Hg. The NO+ mice that were acclimated to hypoxia only showed a 19 mm Hg drop.
Similarly, adaptation to hypoxia protected the NO- mice as well. Without hypoxia, their blood pressure increased ~80 mm Hg. With adaptation, it only increased ~20 mm Hg.
These results indicate that adaptation to hypoxia protects against both over- and under-production of NO.
The body ramps up production of NO while simultaneously increasing NO storage to an even greater extent. This prevents severe drops in blood pressure, but also ensures that NO is available “if needed.”
The final sentence from the abstract sums it up nicely:
“The data suggest that NO stores induced by adaptation to hypoxia can either bind excessive NO to protect the organism against NO overproduction or provide a NO reserve to be used in NO deficiency.”
Adaptation to hypoxia is beneficial in cardiovascular pathology related to NO shortage or overproduction. However, the question about the influence of adaptation to hypoxia on NO metabolism has remained open. The present work was aimed at the relationship between processes of NO production and storage during adaptation to hypoxia and the possible protective significance of these processes. Rats were adapted to intermittent hypobaric hypoxia in an altitude chamber. NO production was determined by plasma nitrite/nitrate level. Vascular NO stores were evaluated by relaxation of the isolated aorta to diethyldithiocarbamate. Experimental myocardial infarction was used as a model of NO overproduction; stroke-prone spontaneously hypertensive rats (SHR-SP) were used as a model of NO shortage. During adaptation to hypoxia, the plasma nitrite/nitrate level progressively increased and was correlated with the increase in NO stores. Adaptation to hypoxia prevented the excessive endothelium-dependent relaxation and hypotension characteristic for myocardial infarction. At the same time, the adaptation attenuated the increase in blood pressure and prevented the impairment of endothelium-dependent relaxation in SHR-SP. The data suggest that NO stores induced by adaptation to hypoxia can either bind excessive NO to protect the organism against NO overproduction or provide a NO reserve to be used in NO deficiency.
Manukhina EB, Mashina SY, Smirin BV, et al. Role of nitric oxide in adaptation to hypoxia and adaptive defense. Physiol Res. 2000;49(1):89-97.