Chronic hypoxia opposes pregnancy-induced increase in uterine artery vasodilator response to flow.

We tested the hypotheses that pregnancy increases the uterine artery (UA) vasodilator response to flow and that this increase is impaired under conditions of chronic hypoxia (30 days, simulated elevation 3,960 m). UA were isolated from 24 normoxic or chronically hypoxic midpregnant guinea pigs and studied with the use of pressure myography. Normoxic pregnancy increased UA flow vasodilator response and protected against a rise in wall shear stress (WSS).

Chronic hypoxia increases MCA contractile response to U-46619 by reducing NO production and/or activity.

Chronic hypoxia alters contractile sensitivity of isolated arteries to alpha-adrenergic stimulation and other agonists. However, most studies have been performed in thoracic aortas or other large vessels making little contribution to vascular resistance in their respective circulations. To determine the effect of chronic hypoxia on the vasoconstrictor response in a small, resistance-sized vessel, we studied second and third generation middle cerebral arteries (MCA; approximately 75-microm internal diameter before mounting).

Differences in membrane ion transport between hepatocytes from the periportal and the pericentral areas of the liver lobule.

We studied the Na+/K+ pump, Na+/K+ ATPase activity, and oxygen consumption (QO2) in hepatocytes isolated from the periportal (PH) and pericentral (CH) regions of the liver lobule, to provide an insight into the functional properties of these cells. Na+/K+ pump activity was determined using 86Rb+ (a functional analog of K+) and ouabain, a specific inhibitor of this transport system. Our results indicate the the Na+/K+ pump and Na+/K+ ATPase activity are significantly lower in CH than in PH, although basal ouabain-sensitive (OS) QO2 was negligible in both of these cell preparations.

Effects of hypothermic perfusion on pulmonary circulation in isolated rabbit lung.

The effects of hypothermic perfusion have been studied by using different perfusates in 24 isolated rabbit lung preparations, divided into three groups: G1, perfused with blood (hematocrit of 10%) and G2 and G3, perfused with erythrocyte-free plasma plus 6% protein in saline. In both G1 and G2 groups left atrial pressures were kept below airway pressure (Zone II conditions), and in G3 it was higher than airway pressure (Zone III conditions). Perfusate flow, pulmonary artery pressure, pulmonary vascular resistance, left atrial pressure, fluid filtration rate, colloid osmotic pressure and temperature were not different (p > 0.

Oxidative capacity distribution in skeletal muscle fibers of the rat.

To study the distribution of oxidative capacity in muscle fibers, mitochondrial volume density and the oxidative capacity of isolated mitochondria were evaluated. Mitochondria were isolated from the subsarcolemmal and interfibrillar areas of the soleus (a muscle largely made up of slow oxidative fibers) and the gastrocnemius medial head (a muscle largely made up of fast glycolytic fibers) of the rat, and their oxidative capacities were evaluated using NADH- and FADH-generating substrates. In the soleus muscle, the subsarcolemmal mitochondria showed a lower oxidative capacity than interfibrillar mitochondria when NADH-generating substrates were used.

Effect of chronic hypoxia on acetaminophen metabolism in the rat.

The effect of chronic hypoxia (10.5% O2 for 8-9 days) on acetaminophen metabolism was studied in vivo or in isolated cell or microsomal systems. Results from in vivo studies with oral administration of acetaminophen showed that in hypoxic rats, the plasma appearance of the drug was delayed and the plasma half-life was increased.

Defining the resistance to oxygen transfer in tissue hypoxia.

Studies of O2 supply in freshly isolated adult mammalian cells provide new insight into the factors that limit mitochondrial oxygenation in vivo. Of particular importance, mitochondria are present at high densities and often in apparent clusters, both of which contribute to local O2 gradients under hypoxic conditions. Current evidence indicates that the mitochondrial distribution is a component of the differentiated phenotype of adult mammalian cells and that specific motors and anchoring mechanisms are present to allow redistribution in response to developmental, physiological and pathological challenges.

Bioavailability of dietary glutathione: effect on plasma concentration.

Plasma glutathione (GSH) concentration in rats increased from approximately 15 to 30 microM after administration of GSH either as a liquid bolus (30 mumol) or mixed (2.5-50 mg/g) in AIN-76 semisynthetic diet. GSH concentration was maximal at 90-120 min after GSH administration and remained high for over 3 h.

Oxidative capacity distribution in the cardiac myocytes of hypermetabolic rats.

To study the distribution of oxidative capacity in the cardiac myocyte in control and in hypermetabolic (hyperthyroid) rats, we evaluated mitochondrial volume density (Vv,mi) distribution by morphometry and oxidative capacity, cytochrome a + a3 concentration and protein yield of isolated subsarcolemmal and interfibrillar mitochondria by biochemical techniques. In control animals Vv,mi underneath the sarcolemma was higher than in the center of the myocytes and it decreased linearly with increasing distance from the capillaries. Interfibrillar mitochondria showed a greater oxidative capacity and a high concentration of cytochrome a + a3 than subsarcolemmal mitochondria.

Muscle capillarity in rats with increased blood oxygen affinity.

To investigate the effects of low P50Hb on muscle capillarity, rats were injected with Na-cyanate (50 mg/kg BW) every day for 2 or 4 weeks (experimental). Controls received injections of saline. After 2 weeks P50 was reduced in the experimental animals (20.

Fiber composition and capillarity in growing guinea pigs acclimated to cold and cold plus hypoxia.

The central portion of the medial head of the gastrocnemius of control (normoxic and normothermic), hypoxia-, cold-, and cold plus hypoxia-acclimated guinea pigs was analyzed for capillary supply and fiber composition to elucidate changes in capillarity induced by environmental stresses. The muscle was cut at midbelly, frozen, sectioned, and stained for myosin ATPase. Fiber cross-sectional areas; percentages of slow-twitch oxidative (SO), fast-twitch oxidative-glycolytic (FOG), and fast-twitch glycolytic (FG) fibers; and numbers of capillaries around each fiber type were measured.

Long-term isoprenaline administration produces an increase in capillarity in the soleus muscle of the rat.

The effects of isoprenaline administration (300 micrograms/kg for 5 weeks) on rat soleus muscle capillarity and glycolytic and oxidative capacities were evaluated. The treatment resulted in ventricular hypertrophy. The activities of lactic dehydrogenase, pyruvate kinase, citrate synthase, and cytochrome c oxidase in soleus muscle homogenates were not different between control and isoprenaline-injected animals.

Changes in soleus muscle capillarity, oxidative capacity and fiber composition in rats recovering from hyperthyroidism.

Soleus muscle oxidative capacity, fiber composition and capillarity were studied in rats that were injected with 300-400 micrograms/kg of triiodothyronine (T3) every other day for 28 days and then left to recover for 4, 8, 14, 21 or 28 days. The activities of cytochrome c oxidase and citrate synthase and the capacity to oxidize pyruvate plus malate of muscle homogenates were 40, 53 and 21% higher than control values at the end of T3 administration. The activity of citrate synthase and the capacity to oxidize pyruvate plus malate decreased rapidly after discontinuing T3 administration, reaching values below those of base line controls in 14 days, but were not different than controls at 21 days.

Capillarity, oxidative capacity and fibre composition of the soleus and gastrocnemius muscles of rats in hypothyroidism.

Muscle capillarity, mean and maximal diffusion distances and muscle fibre composition were evaluated in frozen sections stained for myosin ATPase of the soleus and the white area of the gastrocnemius medial head (gastrocnemius) of rats made hypothyroid by the injection of propylthiouracil (PTU) (50 mg kg-1) every day for 21 or 42 days. Oxygen consumption in the presence of excess ADP and Pi with pyruvate plus malate as substrates and the activity of cytochrome c oxidase were measured in muscle homogenates. Treatment with PTU decreased body oxygen consumption and the concentration of triiodothyronine in plasma.

Capillarity and oxygen diffusion distances of the soleus muscle of guinea pigs and rats. Effects of hyperthyroidism.

The relationship between capillarity and oxidative capacity in the soleus muscle of rats and guinea pigs injected with triiodothyronine (T3) or with saline for up to 4 weeks was studied. The rats' soleus weight and FCSA were not affected by T3, but the guinea pigs that received T3 had smaller muscle weight and FCSA than the controls. The activities of cytochrome c oxidase and citrate synthase were significantly (41 and 65%) higher in the T3 than in the control rats.

The effect of hyperthyroidism on capillarity and oxidative capacity in rat soleus and gastrocnemius muscles.

Muscle fibre composition and capillarity were evaluated in frozen sections stained for myosin ATPase of the soleus and the white area of the medial head of the gastrocnemius of rats made hyperthyroid by injections of triiodothyronine (300-400 micrograms/kg body weight, every other day) for 2, 3 and 4 weeks. O2 consumption of homogenates of these muscles in the presence of excess inorganic phosphate (Pi) and ADP with pyruvate and malate as substrates was also measured. Increased oxidative capacity was observed in the soleus homogenates of hyperthyroid animals after 2 weeks of treatment while no changes were observed in the oxidative capacity of the homogenates of the white area of the medial head of the gastrocnemius, even after 4 weeks of treatment.

Increased capillary supply in skeletal muscle of guinea pigs acclimated to cold.

The ATPase technique was used to visualize blood capillaries and to study fiber composition in 10-micrometer transverse sections of guinea pig gastrocnemius and soleus muscles. A control group of newborn, weanling, juvenile and adult male guinea pigs (GP) (BW = 89-1274 g) was studied in a 20-24 degrees C environment (22 degrees C GP) while 2-3 week old animals were exposed continuously to 5 degrees C for 2-18 weeks before sacrifice (5 degrees C GP) (BW = 239-1074 g). Body weight gain was not affected by cold exposure; however, the gastrocnemius and soleus muscles of the 5 degrees C GP grew at a slower rate than did the muscles of the 22 degrees C GP.

Pulmonary arterial hypertension in male and female chickens at 3300 m.

Two-hundred one-dayy-old male (M) and female (F) chickens were exposed to 3300 m (HA). Two-hundred control chickens were raised at sea level (SL). Chickens from both HA and SL were studied each week from the 3rd to the 7th week of age.

Chronic hypoxia does not affect guinea pig skeletal muscle capillarity.

The soleus and gastrocnemius muscles of chronically hypoxic guinea pigs were analyzed for capillary supply and myoglobin concentration. Weanling male guinea pigs were exposed to a simulated altitude of 5,100 m and an average ambient temperature of 22% C for 2, 4, 6, 10 and 14 weeks (range of BW 244--965 g). The soleus and gastrocnemius-plantaris muscles of one leg were analyzed for myoglobin concentration while the soleus and medial head of the gastrocnemius of the contralateral leg were cut at the midpoint, frozen and sectioned in a cryostat.

Changes in the capillarity of skeletal muscle in the growing rat.

Capillary density (CD), capillary to fiber ratio (C/F), fiber cross sectional area (FCSA) and fiber composition were measured in the soleus and the gastrocnemius (medial head) muscles of rats weighing between 99 and 666 g. Muscle samples obtained from the anesthetized animal were rapidly frozen (-130 degrees C) sliced transversely at 16--18 micrometers, and treated histochemically by the ATPase method after preincubation at pH's of 4.0 and 4.