Hypoxic Rabbits Research Articles

Modalities of fetal evaluation to detect fetal compromise prior to the development of significant neurological damage.

The aim of this study was to clarify the developmental mechanism underlying fetal heart rate (FHR) long-term variability (LTV) and acceleration with respect to fetal brain damage. The fetal state was deduced from the developmental mechanism of FHR variability analyzed by actocardiogram, animal experiments, and simulations. LTV develops due to minor fetal movements in the fetal midbrain, moderate LTV by fetal periodic movements and triangular accelerations by large fetal movement bursts. Stimulation of the fetal midbrain by sound and light produces fetal movements that lead to FHR acceleration. Severe hypoxia can result in the loss of LTV and neuronal necrosis that may damage the fetal brain. Therefore, a cesarean section is recommended prior to the loss of LTV, rather than after its loss. The vagal center of the fetal medulla oblongata is excited by hypoxia and produces FHR bradycardia. The heart rate of hypoxic rabbits was found to be closely correlated with the PaO₂, thus the impact of hypoxia could be estimated by the hypoxia index, which is calculated from the reciprocal of nadir FHR and bradycardia duration. Analyzing the development of FHR signs could help to diagnose fetal state. An early cesarean section is recommended before the loss of LTV as indicated by the hypoxia index, which will contribute to prevent fetal brain damage and neurological sequels.

Myocardial Hypertrophy Overrides the Angiogenic Response to Hypoxia

BackgroundCyanosis and myocardial hypertrophy frequently occur in combination. Hypoxia or cyanosis can be potent inducers of angiogenesis, regulating the expression of hypoxia-inducible factors (HIF), vascular endothelial growth factors (VEGF), and VEGF receptors (VEGFR-1 and 2); in contrast, pressure overload hypertrophy is often associated with impaired pro-angiogenic signaling and decreased myocardial capillary density. We hypothesized that the physiological pro-angiogenic response to cyanosis in the hypertrophied myocardium is blunted through differential HIF and VEGF-associated signaling.Methods and ResultsNewborn rabbits underwent aortic banding and, together with sham-operated littermates, were transferred into a hypoxic chamber (FiO2 = 0.12) at 3 weeks of age. Control banded or sham-operated rabbits were housed in normoxia. Systemic cyanosis was confirmed (hematocrit, arterial oxygen saturation, and serum erythropoietin). Myocardial tissue was assayed for low oxygen concentrations using a pimonidazole adduct. At 4 weeks of age, HIF-1α and HIF-2α protein levels, HIF-1α DNA-binding activity, and expression of VEGFR-1, VEGFR-2, and VEGF were determined in hypoxic and normoxic rabbits. At 6 weeks of age, left-ventricular capillary density was assessed by immunohistochemistry. Under normoxia, capillary density was decreased in the banded rabbits compared to non-banded littermates. As expected, non-hypertrophied hearts responded to hypoxia with increased capillary density; however, banded hypoxic rabbits demonstrated no increase in angiogenesis. This blunted pro-angiogenic response to hypoxia in the hypertrophied myocardium was associated with lower HIF-2α and VEGFR-2 levels and increased HIF-1α activity and VEGFR-1 expression. In contrast, non-hypertrophied hearts responded to hypoxia with increased HIF-2α and VEGFR-2 expression with lower VEGFR-1 expression.ConclusionThe participation of HIF-2α and VEGFR-2 appear to be required for hypoxia-stimulated myocardial angiogenesis. In infant rabbit hearts with pressure overload hypertrophy, this pro-angiogenic response to hypoxia is effectively uncoupled, apparently in part due to altered HIF-mediated signaling and VEGFR subtype expression.

Chronic hypoxia enhances 15-lipoxygenase-mediated vasorelaxation in rabbit arteries

15-Lipoxygenase (15-LO-1) metabolizes arachidonic acid (AA) to 11,12,15-trihydroxyeicosatrienoic acids (THETAs) and 15-hydroxy-11,12-epoxyeicosatrienoic acids (HEETA) that dilate rabbit arteries. Increased endothelial 15-LO-1 expression enhances arterial relaxations to agonists. We tested the effect of hypoxia on 15-LO-1 expression, THETA and HEETA synthesis, and relaxations in rabbit arteries. The incubation of rabbit aortic endothelial cells and isolated aortas in 0.7% O(2) increased 15-LO-1 expression. Rabbits were housed in a hypoxic atmosphere of 12% O(2) for 5 days. 15-LO-1 expression increased in the endothelium of the arteries of rabbits in 12% O(2) compared with room air. THETA and HEETA synthesis was also enhanced in aortas and mesenteric arteries. AA hyperpolarized the smooth muscle cells in indomethacin- and phenylephrine-treated mesenteric arteries of hypoxic rabbits from -29.4 +/- 1 to -50.1 +/- 3 mV. The hyperpolarization to AA was less in arteries of normoxic rabbits (from -26.0 +/- 2 to -37 +/- 2 mV). This AA-induced hyperpolarization was inhibited by the 15-LO inhibitor BW-755C. Nitric oxide and prostaglandin-independent maximum relaxations to acetylcholine (79.7 +/- 2%) and AA (38.3 +/- 4%) were enhanced in mesenteric arteries from hypoxic rabbits compared with the normoxic rabbits (49.7 +/- 6% and 19.9 +/- 2%, respectively). These relaxations were inhibited by BW-755C and nordihydroguaiaretic acid. Therefore, hypoxia increased the relaxations to agonists in the rabbit mesenteric arteries by enhancing endothelial 15-LO-1 expression and synthesis of the hyperpolarizing factors THETA and HEETA.

The effect of hypoxia on the platelet count.

Abstract The occurrence of low arterial oxygen tensions in postoperative patients is well established. The effect of hypoxia on platelets was therefore studied in 36 rabbits. Two groups were exposed to low oxygen mixtures and a third group was exposed to air in an environmental chamber. In all groups the period of exposure was 24 hours. The hypoxic rabbits showed increased platelet counts from the first to nineteenth days after exposure. The difference in counts between both hypoxic groups and the control rabbits was statistically highly significant after exposure. An increase in platelets may well be an important factor in the aetiology of venous thrombosis. It is consequently suggested that a prophylactic régime against thrombo-embolism should include vigorous efforts to prevent hypoxia in the postoperative period.

Analysis of Pulmonary Vascular Response to Acute Alveolar Hypoxic Challenge in Young Rabbits Subjected to Chronic Hypoxia from Birth

Chronic alveolar hypoxia induces vascular changes leading to pulmonary hypertension. We investigated the role of nitric oxide synthase (NOS) on basal pulmonary artery pressure (PAP) and on changes in PAP arising from an acute alveolar hypoxic challenge (AAHC) in normoxic and chronically hypoxic young rabbits. The chronically hypoxic rabbits were raised from birth in a chamber containing a (10% O2 + 90% N2) gas mixture, whereas the normoxic rabbits were kept in room air. The age of the animals at the time of study (approximately 38 days) was not significantly different between the 2 groups of rabbits. The in vivo PAP was measured using a right heart catheterization technique while the rabbits were spontaneously breathing either a hyperoxic or a hypoxic gas. In the chronically hypoxic group, the AAHC (hypoxic gas) produced a modest increase in PAP. However, after intravenous administration of (100 mg/kg) of the NOS inhibitor, L-NAME (N-nitro-L-arginine methyl ester), a marked increase in PAP was observed when these rabbits were rechallenged with the AAHC. In contrast, in the normoxic rabbits, the AAHC produced only a small increase in PAP, even after pretreatment with L-NAME. In both groups of rabbits, L-NAME led to a significant rise in basal PAP. Using Western blot analysis, we found endothelial NOS (eNOS) protein expression to be significantly increased in pulmonary artery and right ventricular myocardium of the chronically hypoxic rabbits. These results suggest that release of nitric oxide is involved in regulating basal PAP and in modulating the hypoxia-induced pulmonary vasoconstrictor response in immature animals. Moreover, eNOS appears to undergo up-regulation as a consequence of chronic hypoxia.

Cardioprotection in chronically hypoxic rabbits persists on exposure to normoxia: role of NOS and KATP channels.

Hypoxia from birth increases resistance to myocardial ischemia in infant rabbits. We hypothesized that increased cardioprotection in hearts chronically hypoxic from birth persists following development in a normoxic environment and involves increased activation of nitric oxide synthase (NOS) and ATP-dependent K (K(ATP)) channels. Resistance to myocardial ischemia was determined in rabbits raised from birth to 10 days of age in a normoxic (Fi(O(2)) = 0.21) or hypoxic (Fi(O(2)) = 0.12) environment and subsequently exposed to normoxia for up to 60 days of age. Isolated hearts (n = 8/group) were subjected to 30 min of global ischemia followed by 35 min of reperfusion. At 10 days of age, resistance to myocardial ischemia (percent recovery postischemic recovery left ventricular developed pressure) was higher in chronically hypoxic hearts (68 +/- 4%) than normoxic controls (43 +/- 4%). At 10 days of age, N(G)-nitro-L-arginine methyl ester (200 microM) and glibenclamide (3 microM) abolished the cardioprotective effects of chronic hypoxia (45 +/- 4% and 46 +/- 5%, respectively) but had no effect on normoxic hearts. At 30 days of age resistance to ischemia in normoxic hearts declined (36 +/- 5%). However, in hearts subjected to chronic hypoxia from birth to 10 days and then exposed to normoxia until 30 days of age, resistance to ischemia persisted (63 +/- 4%). L-NAME or glibenclamide abolished cardioprotection in previously hypoxic hearts (37 +/- 4% and 39 +/- 5%, respectively) but had no effect on normoxic hearts. Increased cardioprotection was lost by 60 days. We conclude that cardioprotection conferred by adaptation to hypoxia from birth persists on subsequent exposure to normoxia and is associated with enhanced NOS activity and activation of K(ATP) channels.

87 Effect of Body Warming on Blood Flow Distribution in Hypoxic Infant Rabbits

87 Effect of Body Warming on Blood Flow Distribution in Hypoxic Infant Rabbits

Hypoxia-induced down-regulation of CYP1A1/1A2 and up-regulation of CYP3A6 involves serum mediators.

1. Acute moderate hypoxia modifies the catalytic activity and expression of certain isoenzymes of hepatic cytochrome P450 (P450). The aim of this study was to document whether hypoxia affects hepatic P450 directly or through the release of serum mediators. 2. Rabbits were subjected to a FiO(2) of 8% for 48 h, sacrificed, and serum and hepatocytes were isolated; hepatocytes from control and rabbits with hypoxia were incubated with serum from control and hypoxic rabbits for 4 and 24 h, and total P450 content, CYP1A1, 1A2 and 3A6 activities and expressions were assessed. Sera were fractionated by size exclusion chromatography and fractions tested for their ability to modify activity and amount of P450, and serum mediators were identified through neutralization experiments. 3. Total serum and fractions with proteins of 15-23 and 65-94 kDa of M(r) reduced P450 content and expression of CYP1A1, 1A2 and 3A6, as well as CYP1A1, 1A2 and 3A6 mRNA. Total serum and the fraction with 32-44 kDa proteins increased CYP3A6 activity and protein and mRNA. The serum mediators implicated in the decrease in activity and expression of CYP1A1, 1A2 and 3A6 were interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta) and IL-2. Erythropoietin (Epo) was partly responsible for the increase in P450 content and CYP3A6 expression. 4. In conclusion, acute moderate hypoxia diminishes the activity and expression of CYP1A1, 1A2 and CYP1A1, 1A2 mRNA, and increases CYP3A6 protein, activity and CYP3A6 mRNA. Several mechanisms contribute to these changes in P450, among them the release of cytokines acting as serum mediators.

20 Persistence of cardioprotection in chronically hypoxic rabbits exposed to normoxia: Role of nitric oxide synthase

20 Persistence of cardioprotection in chronically hypoxic rabbits exposed to normoxia: Role of nitric oxide synthase

Effect of exposure to hypoxia from birth on aldosterone in rabbits: role of unesterified fatty acids

Hypoxia and fluid and electrolyte disturbances are serious risks to normal postnatal development. Because a decrease in inspired O2 (hypoxic hypoxia) inhibits aldosterone synthesis in the adult and aldosterone controls water and electrolyte balance, we studied adrenocortical function in rabbits exposed to normobaric normoxia or hypoxic hypoxia (fraction of inspired O2 0.09) from birth. At 21 days of age, rabbits were anesthetized, the adrenals were rapidly removed, and the adrenal capsules containing mostly zona glomerulosa cells were separated. Cells were dispersed with collagenase and studied in vitro. Hypoxia in vivo resulted in a 73% decrease in basal aldosterone release and a 86% decrease in adenosine 3',5'-cyclic monophosphate-stimulated aldosterone release in vitro. We hypothesized that increased unesterified fatty acids could be partly responsible for inhibition of aldosterone synthesis. Total serum unesterified fatty acids in hypoxic kits were significantly increased (298 +/- 14 micromol/l) compared with normoxic kits (184 +/- 31 micromol/l). When cells from hypoxic rabbits were washed with fatty acid-free albumin and studied under conditions devoid of fatty acids, aldosterone production was partially restored. Corticosterone production was not affected by washing. Washing had no effect on aldosterone synthesis by cells from normoxic rats. Finally, exposing washed zona glomerulosa cells to oleic acid (10-50 microM) inhibited aldosteronogenesis. We conclude that exposure to hypoxia from birth attenuates aldosterone production in part due to an increase in levels of unesterified fatty acid levels.

Dose-dependent effect of inhaled nitric oxide on pulmonary oxygenation differs from the effect on pulmonary circulation in hypoxic rabbits

Dose-dependent effect of inhaled nitric oxide on pulmonary oxygenation differs from the effect on pulmonary circulation in hypoxic rabbits

Effects of an early postnatal hypoxia on the development of spontaneous head movements in rabbits.

The early detection of minor brain dysfunctions resulting from perinatal hypoxia is very important since the prognosis of the affected children can be substantially improved by a prompt treatment. Therefore, this paper deals with the influence of an early postnatal hypoxia on the postnatal development of spontaneous head movements and the influence of the visual system on head movements in normal and hypoxic disturbed ontogenesis. Head movements were recorded in 12 unrestrained spontaneously behaving alert rabbits from 6 litters with the sensor coil technique. One rabbit of each litter was exposed to a single acute hypoxia (FiO2 = 0.05) for 3 h at the 1st day of life. The siblings were regarded as a control group. The most important characteristic of the postnatal development of the head movements is the forming of horizontal saccadic movements during the second postnatal week and their perfection by an increase in mean velocity up to the 20th postnatal day. The early postnatal hypoxia leads to a decrease of the mean velocity of saccadic head movements. But this is only true if the rabbits have open eyes. Blind-folding the rabbits of the control group during the recordings was followed by a decrease of the mean velocity (14th and 20th postnatal day) and the amplitude (at the 20th postnatal day) of the saccadic head movements. In contrast to the non-hypoxic rabbits, blind-folding had no perceptible influence on head movements in hypoxic rabbits until the 3rd postnatal week. Our results suggest that early postnatal hypoxia causes a

Effect of atrial natriuretic peptide on bronchial tone in anesthetized rabbits

The effect of atrial natriuretic peptide (ANP) on histamine-induced bronchoconstriction was studied in vivo (in normoxic and in hypoxic rabbits) and in vitro. Thirty-two anesthetized rabbits, spontaneously breathing room air or 10% O 2, received infusions of ANP (20, 40, or 80 ng/min/kg normoxia; 20 ng/min/kg hypoxia) or the vehicle for 100 min. After 75 min of ANP infusion, bronchoconstriction was induced inhaling histamine; respiratory resistance (Rrs) was measured prior to and until 20 min posthistamine. The results show that the histamine-induced increase in Rrs was significantly reduced by ANP 80 ng/kg/min in normoxia, and by ANP 20 ng/kg/min in hypoxia. In vitro, ANP had no effect on tracheal and bronchial smooth muscle precontracted with histamine or acetylcholine. These results show that ANP can decrease a histamine-induced bronchoconstriction in vivo but not in vitro, suggesting an indirect mechanism of action.

The earliest histopathological response to hypobaric hypoxia in rabbits in the rifugio torino (3370 M) on Monte Bianco

Twelve Dutch rabbits were kept on Monte Bianco at an altitude of 3370 m. Half of the animals were killed after 3 months, the remainder after 6 months, and a further six animals maintained at sea-level acted as controls. The carotid bodies of all the rabbits were processed for light and electron microscopy and examined qualitatively and quantitatively. The lungs were processed for light microscopical assessment of small pulmonary arterial vessels; the thickness of the pulmonary trunks and aortas were measured; and the hearts were dissected to obtain ratios of the ventricular weight. There was a slight increase in the right ventricular weight in the hypoxic rabbits but no change in the thickness of the pulmonary trunk compared with that of the aorta. In particular, there was no hypoxic remodelling of the pulmonary vasculature such as muscularization of pulmonary arterioles or intimal longitudinal muscle in pulmonary arteries. The earliest histopathological response to hypoxia occurred in the carotid bodies in the form of an increase in the count of the dark variant of chief cell after 3 months which returned to normal after 6 months. It is concluded that the carotid body of the rabbit responds with a change in its population of dark chief cells to a level of hypoxia which is insufficient to affect the pulmonary arterioles. Changes in the cardiopulmonary system can no longer be considered to be the earliest histopathological response to hypobaric hypoxia.

Eicosanoids in hypoxic insult to neonatal rabbit bowel.

Eicosanoids, derivatives of arachidonic acid, play a role in several inflammatory diseases of the bowel. To determine whether prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and leukotriene C4D4E4 (LTC4D4E4), have a role in hypoxic insult to the intestine, we examined the levels of these mediators in a hypoxic neonatal rabbit model. One group of animals underwent hypoxic insult postnatally, the second group did not undergo hypoxia and served as a control. The levels of PGE2, LTB4, and LTC4D4E4 were determined by radioimmunoassay. PGE2 in the hypoxic group was 1,779 +/- 142 pg/mg protein (mean +/- SD) as opposed to 2,380 +/- 197 pg/mg protein in the control group (p less than 0.02). LTB4 level was 5,446 +/- 3,492 pg/mg protein in the hypoxic rabbits and 3,362 +/- 2,570 pg/mg protein in the control group (p less than 0.03). There was no statistically significant difference in the level of LTC4D4E4 between the two groups. Our study shows that hypoxia shifts the arachidonic acid metabolism toward enhanced lipoxygenase activity with a resultant increase in LTB4 levels and a concomitant decrease in cyclooxygenase activity with reduced PGE2 levels in the bowel. The shift in the balance between these eicosanoids may play a role in the pathogenesis of ischemic-hypoxic bowel diseases by enhancing the inflammatory response in the intestine, and simultaneously, diminishing cytoprotection.

Eicosanoids in Hypoxic Insult to Neonatal Rabbit Bowel

SummaryEicosanoids, derivatives of arachidonic acid, play a role in several inflammatory diseases of the bowel. To determine whether prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and leukotriene C4D4E4 (LTC4D4E4), have a role in hypoxic insult to the intestine, we examined the levels of these mediators in a hypoxic neonatal rabbit model. One group of animals underwent hypoxic insult postnatally, the second group did not undergo hypoxia and served as a control. The levels of PGE2, LTB4, and LTC4D4E4 were determined by radioimmunoassay. PGE2 in the hypoxic group was 1,779± 142 pg/mg protein (mean± SD) as opposed to 2,380± 197 pg/mg protein in the control group (p < 0.02). LTB4 level was 5,446± 3,492 pg/mg protein in the hypoxic rabbits and 3,362± 2,570 pg/mg protein in the control group (p < 0.03). There was no statistically significant difference in the level of LTC4D4E4 between the two groups. Our study shows that hypoxia shifts the arachidonic acid metabolism toward enhanced lipoxygenase activity with a resultant increase in LTB4 levels and a concomitant decrease in cyclooxygenase activity with reduced PGE2 levels in the bowel. The shift in the balance between these eicosanoids may play a role in the pathogenesis of ischemic‐hypoxic bowel diseases by enhancing the inflammatory response in the intestine, and simultaneously, diminishing cytoprotection.

Effects of Chronic Hypoxia during Maturation on the Negative Chronotropic Effect of [H<sup>+</sup>] on the Rabbit Sino-Atrial Node

Previous studies in our laboratory have shown an effect of 12 weeks of hypoxia on the electrophysiology of the heart. This study was designed to determine the effects of hypoxia for shorter periods (1, 2, 3 and 6 weeks) on the neonatal heart as well as the chronotropic effects of [H+] on sino-atrial automaticity. Rabbits (2 days of age) were raised for 1, 2, 3 or 6 weeks in either a normal or hypoxic environment. At the end of 1, 2, 3 or 6 weeks, they were killed and studied using an isolated sino-atrial tissue preparation and standard microelectrode techniques. Measurements of hematocrit, ventricular weight and ventricular total protein were made. Right ventricular hypertrophy appeared at 2 and 3 weeks in the hypoxic hearts. There was no difference in left ventricular weight or total protein between normal and hypoxic groups over the time studied. Both the basal and maximal (isoproterenol stimulated) spontaneous rates decreased with age. The baseline and maximal rates from hypoxic rabbits were significantly less than those from normal rabbits at 3 and 6 weeks (p less than 0.05). The net negative chronotropic effect of elevated [H+] was more pronounced in the hypoxic than the normal preparations at 3 and 6 weeks. In summary, neonates raised in hypoxia for as short a period as 3 weeks show right ventricular hypertrophy and a decrease in sino-atrial automaticity. The net negative chronotropic effect of [H+] is enhanced with development and chronic hypoxia.

Physiological chemoreceptor stimulation decreases enkephalin and substance P in the carotid body

Neuroactive peptides, including the enkephalins (Met- and Leu-enkephalin; ME, LE) and substance P (SP) are known to be present in the mammalian carotid body, an arterial chemoreceptor organ sensitive to the O 2, CO 2 and pH levels in blood. The principal parenchymal (type I) cells of the organ, which receive sensory innervation from the carotid sinus nerve (CSN), have been shown to contain both ME and SP; SP is also present in CSN afferent fibers. In the present study, rabbits were exposed in a chamber to a physiological chemoreceptor stimulus (5% O 2 in N 2) for one hour, then anesthetized during surgical removal of both carotid bodies for later RIA measurement of ME and SP levels in the tissue; control animals were exposed to air in the chamber, but otherwise treated as the hypoxic animals. Both ME and SP levels were significantly reduced (approximately 40%) in the carotid bodies from hypoxic rabbits, compared to their normoxic controls. The results suggest that these neuroactive peptides are released from carotid body elements during physiological stimulation, and consequently may play a role in the transduction of chemosensory information between the type I cells and their apposed afferent terminals.

On the seemingly diminished CO2-Bohr effect in hypoxic chemodenervated rabbits.

In hypoxic rabbits, different levels of Pco2 before and after carotid chemodenervation were applied in order to get information about the acid-base status and the position of the O2-Hb dissociation curve (ODC). A CO2-induced change in pH caused a smaller change in the half-saturation pressure (P50) than was to be expected from the CO2-Bohr effect alone. Considering both, the numerically different CO2- and fixed acid-Bohr factors as well as the corresponding respiratory or metabolic pH changes, a method is presented to calculate the position of the ODC with high accuracy. From these considerations it can be derived that the seemingly diminished CO2-Bohr effect in hypoxic rabbits in vivo, especially after chemodenervation , is due more or less to accumulation of lactid acid. This leads to an increasing error if only the CO2-Bohr factor and the actual pH change are taken into account.

遺伝性高脂血症ウサギ(WHHL-rabbit)における動脈硬化性病変に及ぼす高酸素ならびに低酸素吸入の影響

The present study was carried out to investigate the effects of systemic hyperoxia and hypoxia on plasma lipids and atherogenesis in WHHL-rabbits which showed marked hypercholesterolemia and hypertriglyceridemia from birth.Of 15 male WHHL-rabbits (2-3 months old), six rabbits were exposed to 40% oxygen (hyperoxic) and five were exposed to 10% oxygen (hypoxic) for five hours daily on five days of each week for eight weeks. Four rabbits without such exposure were used as controls. The results were as follows:1) The levels of plasma cholesterol were not affected significantly by the hyperoxic and hypoxic exposure throughout the experimental period. Therefore, the average plasma cholesterol levels in the three groups indicated almost the same values.2) The levels of plasma triglycerides increased significantly by systemic hypoxia but were not affected by hyperoxia, and the average plasma triglyceride values were higher in the hypoxic rabbits than in the hyperoxic or control rabbits.3) The ratio of the area of sudanophilic lesions to the total intimal area of the aorta were lower in the hyperoxic rabbits, and higher in the hypoxic rabbits than in the controls. The differences between the hyperoxic and hypoxic groups were significant.4) There were no significant correlations between the extent of the aortic lesions and the levels of plasma cholesterol or triglycerides.From these results, it is suggested that the progress of atherosclerotic changes of the aorta is suppressed or promoted by systemic hyperoxia or hypoxia, respectively, not through the changes in the plasma lipid levels, but through the direct effects on the aortic wall.