Role of Nitric Oxide in Adaptation to Hypoxia and Adaptive
Defense E.B. Manukhina1, S.Yu. Mashina1, B.V. Smirin1, N.P.
Lyamina2, V.N. Senchikhin2, A.F. Vanin3, I. Yu. Malyshev1
1Institute of General Pathology and Pathophysiology, Moscow, 2Saratov Institute of Cardiology, Saratov and 3Institute
of Chemical Physics, Moscow, Russia
Received July 30, 1999
Accepted September 21, 1999
Summary
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.
Key words
Nitric oxide · Adaptation · Hypoxia · Spontaneously hypertensive rats · Myocardial
infarction
Reprint requests
Prof. Eugenia B. Manukhina, Institute of General Pathology and Pathophysiology, Moscow
125315, Russia. e-mail: manukh@orc.ru
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