Adaptation of rats to short-term immobilization stress increases the ability of their isolated organs to generate nitric oxide (NO): its spontaneous release by the liver, gut, heart, and kidney tissues rises 2-to 4-fold and its carbachol-stimulated release by these tissues rises 4-to 5-fold. It is suggested that such adaptation leads to rapid NO generation in the adapted animal in response to exogenous or endogenous stimuli and thus increases the efficacy of defense reactions. Key Words: nitric oxide; adaptation to stressIt has been established that increased (within physiological limits) generation of nitric oxide (NO) may play a substantial role in many defense reactions of the body. Thus, macrophage-generated NO is cytotoxic to blastomatous and bacterial cells [7], and the increased generation of NO from compounds introduced into the body results in the dilatation of coronary vessels and can thus eliminate or limit the damage caused to the heart by ischemia or reperfusion [11]. NO has also been shown to modulate sympathetic effects [6] and to exhibit antimitogenic activity [5]. On the other hand, adaptation to repeated stress factors, which is our concern here, not only protects from stressinduced damage as such [2] but also produces a wide range of protective cross-effects. It can, for example, protect the heart from ischemia-and reperfusion-induced damage [2], modulate the regal- latory adrenergic effects on resistive vessels in favor of their dilatation [3], and exert a strong protective effect in sublethal hypoxia [4].These similarities between the protective effects of stress adaptation and the physiological effects of NO suggest that adaptation to multiple noninjurious stress may increase the power of the NO-generating system in organs and tissues, thereby augmenting NO generation, both spontaneous and stimulated.The purpose of this study was to explore how preliminary adaptation to short-term immobilization stress might influence spontaneous and carbachol-stimulated NO generation by tissues of internal organs in rats. MATERIALS AND METHODSMale Wistar rats weighing 200-230 g were used for the experiment. A course of adaptation consisted of eight exposures on alternate days to stress produced by immobilizing the animals on the back with fixed limbs. The first exposure lasted 15 min, the second 30 rain, the third 45 min, and the other five 60 min each. The tests were started 48 h af-

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Adaptation to intermittent hypoxic hypoxia did not affect the endothelium-dependent relaxation of the aorta in rats, but significantly increased the relaxation of their tail artery. Following the adaptation, the NO level fell in the liver, intestine, and kidneys and remained unchanged in the spleen. Adaptation to hypoxia presumably limits NO synthesis and/or release in the vascular endothelium or enhances the capacity of this oxide to bind in a physiologically active depot. Key Words: adaptation to hypoxia; nitric oxide; endothelial relaxation factor; endotheliumdependent relaxation; tail arteryNitric oxide (NO), which is the active principle of endothelial relaxation factor, is known to play a pivotal role in the prevention of excessive vasoconstriction. Diminished NO production by vascular endothelium is an important factor in the pathogenesis of several diseases (e.g., hypertension and angina pectoris) in which vascular tone is increased [10]. On the other hand, excessive production of endothelial relaxation factor may lead to drastic falls in the vascular tone and systemic arterial pressure (AP), as is observed to occur in myocardial infarction and severe stress [1,4] and in different forms of shock [10]. Hence the importance of finding agents that can correct and prevent such conditions without disturbing the endothelium-mediated responses of vessels and systemic AP. One agent of this type is intermittent hypoxia, adaptation to which, as shown in animal studies, inhibits the development of experimental hypertension tion as a result of excessive NO production by the endothelium [1], but does not alter AP in normal animals [9]. However, the mechanisms of such dissimilar effects produced by adaptation to hypoxia remain unexplored. In the present study on rats we compared the effect of adaptation to intermittent hypoxia on endothelium-dependent vessel relaxation with its effect on the production of NO, the mediator of this relaxation. MATERIALS AND METHODSMale Wistar rats weighing 300-330 g were used. They were adapted to hypoxic hypoxia in a hypobaric chamber. The adaptation course consisted of 35 daily sessions of 4 h each at an "altitude" of 1000 m on day 1, 2000 m on day 2, 3000 m on day 3, and 4000 m on days 4-35. Rats unadapted to hypoxia served as controls. The rats were killed by decapitation 48 h after the last session. In one series of tests, a 3-mm-wide circular preparation of the thoracic aorta from each rat was placed in the working chamber of an "organ-bath" system (Ugo Basile) filled with a continuously oxygenated Krebs solution at 37~ The initial tension was 1200 mg. Endothelium-dependent relaxation of the aorta was

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