No abstract

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 4.4 to visualize capillaries and typify fibers. In both muscles the FCSA was positively related to body weight (BW) and muscle weight. At a given BW, the FCSA of the soleus was greater than that of the gastrocnemius. In both muscles CD decreased hyperbolically with FCSA (soleus: CD = 1.0613 X 10(6)/FCSA + 298.71; gastrocnemium: CD = 1.0349 X 10(6)/FCSA + 240.74). At the same time a positive linear correlation between C/F and FCSA was found (soleus: C/F = 3.92 X 10(-4) FCSA + 0.82; gastrocnemius: C/F = 2.90 X 10(-4) FCSA + 0.93). At a given FCSA, CD and C/F were greater in the soleus than in the gastrocnemius because of differences in fiber composition between the two muscles. The soleus had only oxidative fibers (STO and FTOG) whereas the gastrocnemius had 54% glycolytic fibers (FTG). The very large variability in CD and C/F values reported in the literature could, in part, be due to the differences in capillarity observed with maturation. A change in fiber composition with BW was observed in the soleus, but no systematic change occurred in the gastrocnemius.

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. Administration of the amino acid precursors of GSH had little or no effect on plasma GSH values, indicating that GSH catabolism and resynthesis do not account for the increased GSH concentration seen. Inhibition of GSH synthesis and degradation by L-buthionine-[S,R]-sulfoximine and acivicin showed that the increased plasma GSH came mostly from absorption of intact GSH instead of from its metabolism. Plasma protein-bound GSH also increased after GSH administration, with a time course similar to that observed for free plasma GSH. Thus dietary GSH can be absorbed intact and results in a substantial increase in blood plasma GSH. This indicates that oral supplementation may be useful to enhance tissue availability of GSH.

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 opposed these effects, prompting vasoconstriction at high flow and increasing WSS above levels seen in normoxic pregnant UA. The nitric oxide synthase inhibitor N(G)-nitro-l-arginine (l-NNA) eliminated the pregnancy-associated increase in flow vasodilation in normoxic UA, suggesting that increased nitric oxide production was responsible. The considerable residual vasodilation after nitric oxide synthase and cyclooxygenase inhibition implicated endothelial-derived hyperpolarizing factor (EDHF) as an additional contributor to flow vasodilation. l-NNA increased flow vasodilation in UA from chronically hypoxic animals, suggesting that chronic hypoxia may have lowered EDHF or elevated peroxynitrite production. In conclusion, flow is an important physiological vasodilator for the acute and more chronic UA dimensional changes required to increase uteroplacental blood flow during normal pregnancy. Chronic hypoxia may be a mechanism that opposes the pregnancy-associated rise in UA flow vasodilation, thereby increasing the incidence of preeclampsia and intrauterine growth restriction at a high altitude.

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. Pulmonary arterial pressure (Ppa) was measured under local anesthesia in conscious animals. Hb, Hct and red blood cell counts (E) and the weights of the right ventricle (RV), left ventricle (LV) and septum (S) were obtained. HA chickens, both males and females, reached lower body weights than SL chickens. Ppa were 16 and 43 mm Hg (2.13 and 5.73 kPa) while RV/(RV + LV + S) values were 0.195 and 0.347 in SL and HA chickens, respectively. RV was 90% greater and LV 20% smaller in the HA chickens. S was not affected by altitude. Hb, Hct and E were higher in the HA birds. Sixteen HA M and 1 HA F died with signs of right heart insufficiency (RHI), however, M did not show greater values of Ppa or RV/(RV + LV + S) than F at SL or at HA. This indicates that the higher incidence of RHI in the M cannot be attributed to a higher responsiveness of their pulmonary vasculature to hypoxia.