摘要:

Exercise training improves maximal oxygen uptake and endurance times in adult human beings and other animals. The mechanism of this improvement results in part from anabolic effects of exercise and may be mediated by growth hormone (GH). Little is known about the role of GH in the adaptation to exercise in younger, still-developing organisms. To examine this role, we began a 4-wk treadmill exercise training protocol in 14-d-old female rats. GH was suppressed by passive immunization with anti-GH releasing hormone antisera. There were four experimental groups:1) GH-control (normal GH secretory capacity), untrained (n= 21);2) GH-suppressed. untrained (n= 13);3) GH-control, trained (n= 14); and4) GH-suppressed; trained (n= 11). At the end of the training period, maximal oxygen uptake and treadmill endurance running time were measured. Serum GH and IGF-I were assessed using RIA, and whole hind limb musculature succinate dehydrogenase (an indicator of mitochondrial function) was measured with standard fluorometric technique. Body weight gain was markedly reduced in GH-suppressed rats (mean, 54% of GH-controls in untrained rats and 55% in trained;p< 0.05). No apparent effect of training on linear growth was observed. As expected, serum IGF-I was markedly reduced by GH suppression, but no exercise-induced increase occurred in IGF-I as a result of training in either the GH-control or GH-suppressed rats. In GH-control rats, maximal oxygen uptake and succinate dehydrogenase were 69% and 25% greater, respectively, in trained compared with untrained rats (p< 0.05). Despite GH inhibition, similar increases were found in the trained GH-suppressed rats (68% greater than controls for maximal oxygen uptake and 34% for succinate dehydrogenase,p< 0.05). Thus, marked improvement in cardiorespiratory function occurs with training in young female rats even when normal pituitary GH function is suppressed.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Using anin situisolated salt-perfused rabbit lung preparation, we investigated the functional ontogeny of pulmonary vascular dopamine receptors. In rabbits from 1 to 23 d of age, we measured pulmonary vascular vasodilator) responses to the peripheral vascular dopamine receptor (DA1) agonist, fenoldopam, and sodium nitroprusside during prostaglandin F2α-induced pulmonary vasoconstriction. In separate experiments, the lungs were pretreated with the DA1receptor blocker, SCH 23390, before prostaglandin F2α, fenoldopam, and sodium nitroprusside. Lungs from rabbits at one of 6 age groups (n= 6–8 per group) were ventilated and perfused. After a stabilization period, prostaglandin F2αwas infused into the pulmonary inflow catheter in a concentration range to yield a sustained rise in mean pulmonary artery pressure (4.9 ± 0.2 mm Hg). Fenoldopam was injected into the pulmonary artery at doses of 0.01, 0.1, 1.0, and 10 μg/g after a recovery period, sodium nitroprusside (0.2 μg/g) was injected into the pulmonary artery, and the resultant changes in vascular pressure were recorded. Across all age groups, with and without DA1receptor blockade, sodium nitroprusside–induced vasodilation was similar (–2.7 ± 0.2 mm Hg) and was considered reference vasodilation. The fenoldopam vasodilation response was considered a percentage of the sodium nitroprusside reference. Response to fenoldopam varied significantly (p< 0.05 by analysis of variance) across the six age groups, with a maximum at 3–5 d of age. Pretreatment with SCH 23390, a selective DA1-blocking agent, significantly attenuated fenoldopam vasodilation in all but the youngest animals (age 0–2 d), in which no blockade effect was noted. We conclude that there are significant age-related changes in the vascular responses to fenoldopam. We speculate that endogenous dopamine and vascular dopamine receptors may play a role in mediating changes in the transitional, pulmonary circulation.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Because fetal rat lungs have lower baseline levels of both surfactant and antioxidant enzymes than full-term newborn rats, we questioned whether prematurely delivered rats might be more susceptible to O2toxicity than those born at term. In the present studies, prematurely delivered rats (gestational d 21 of 22) and full-term rat pups were simultaneously put in > 95% O2after birth. Surprisingly, we found that the preterm rats were not more susceptible to O2-induced lung damage and lethality than full-term newborns, but, in fact, the composite percentage of survival was even greater in the preterm pups from 7 to 9 d in hyperoxia and were similar thereafter up to 14 d in high O2. In addition, the preterm rats showed significantly decreased lung wet/dry weight ratios and consistently less severe pathologic evidence of pulmonary edema compared with term rats at 6 and 8 d of O2exposure. The premature pups demonstrated the capability of inducing pulmonary antioxidant enzyme responses to hyperoxia by 3 d, and had significantly elevated copper-zinc superoxide dismutase, catalase, and glutathione peroxidase activities (and lung surfactant contents) at 6 d of O2exposure compared with the term rats in O2. The rates of lung total O2consumption and cyanide-resistant O2consumption at d 6 in hyperoxia were not different for pretermversusterm pups. Although the basis for the transiently improved survival and decreased evidence of pulmonary O2toxicity in the preterm rats is presently unknown, these findings clearly indicate that premature animals of at least one species are equally able to induce protective lung antioxidant enzymes and surfactant responses to hyperoxia as full-term newborn animals.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Increased deposition of hyaluronan (HA) is part of the early response to fibrogenic stimulus in the lung exposed to bleomycin injury and has been associated with increased lung water in adult animals. Early respiratory distress syndrome (RDS) in premature infants is characterized by increased lung water, and late sequelae include fibrosis or bronchopulmonary dysplasia. We hypothesized that increased MA in the alveolar interstitium would be associated with increasingly severe RDS in prematurely delivered monkeys and that modes of therapy that affect severity of disease such as treatment with high-frequency oscillatory ventilation or exogenous surfactant would decrease this response. Thirty-fourMacaca nemestrinamonkeys were delivered at 134 ± 1 d (term = 168 d) and randomized to high-frequency oscillatory ventilation or conventional mechanical ventilation from birth. Sixteen of these animals received surfactant. At 6 h of age, the right lower lung was frozenin situduring inflation to 30 cm H2O (approximately 2940 Pa) and then dehydrated and processed for microscopy. The presence and severity of RDS were evaluated by clinical and morphologic criteria. HA concentrations in lung extracts increased with progressively severe RDS (p= 0.0003). Treatment with high-frequency oscillatory ventilation decreased the lung injury score (1.69 ± 0.7 compared with 2.5 ± 0.9,p= 0.05), but changes in lung HA concentration did not reach significance (37.9 ± 22.7 compared with 44.8 ± 22.6). Surfactant treatment decreased lung HA concentration (29.6 ± 19.0 μg/wet lung) compared with non-surfactant-treated animals (54.7 ± 20.2 μg/g wet lung,p= 0.0009). Two fetal animals (144 and 163 d gestation) and seven additional premature animals ventilated for up to 96 h were compared with the animals killed at 6 h. HA concentrations increased with length of mechanical ventilation and severity of illness in these animals. HA was localized in freeze-dried lung sections using a biotinylated probe. Lung sections were blindly scored for the distribution of HA staining, and these scores were positively correlated with HA concentration measurements (r= 0.75,p< 0.0001). The quantity of HA in alveolar microvasculature correlated with severity of RDS (r= 0.68,p= 0.0004). We conclude that1) HA concentration in RDS lungs of prematurely delivered infant monkeys is increased relative to normal lungs at 6 h,2) increased HA is localized predominantly to the perivascular space of lung vasculature, and3) this response is decreased by surfactant treatment.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

We performed intracardiac electrophysiologic studies of the effects of vasoactive intestinal peptide (VIP, 0.125 μg/kg/min) on sinus and atrioventricular (AV) nodal function, intracardiac conduction, and myocardial refractoriness in two groups of neonatal dogs (aged 6–16 d). Group I consisted of eight neonates in whom VIP was administered after bilateral vagotomy and β-blockade with propranolol. Group II consisted of five neonates studied after vagotomy and propranolol, plus total chemical sympathectomy (6-hydroxydopamine). In both groups, VIP resulted in a significant shortening of sinus cycle length. AV nodal conduction time, measured as the AH interval (the time from the onset of the atrial electogram to the onset of the His bundle electrogram in the His electrode catheter) during atrial pacing, also shortened after VIP. His-Purkinje conduction time and atrial effective refractory periods were unchanged by VIP. In other experiments, the direct chronotropic effect of VIP was evaluated in five isolated neonatal canine hearts using a modified Langendorff technique. In these hearts, the spontaneous cycle length decreased from 403 ± 88 to 293 ± 69 ms, or −28 ± 4% (mean ± SD), after exposure to 0.1–0.5 nmol of VIP (p< 0.001). In nine other newborns (aged 4–16 days), the effect of selective α1- and α2-adrenergic receptor blockade on the positive chronotropic effect of VIP was evaluated. The effect of VIP on sinus cycle length was not altered by the α2-adrenergic receptor blocker prazosin or by the α2-adrenergic receptor blocker yohimbine. These data indicate that, in the neonatal dog, VIP shortens sinus cycle length and AV nodal conduction time but has no effect on infranodal conduction or myocardial refractoriness. We find no evidence that VIP's chronotropic effect is modified by α-adrenergic receptor blockade. VIP may play a role in the neural modulation of heart rate and AV nodal conduction in the neonate.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Significant fluctuations in heart rate (HR) and arterial pressure occur during fetal life. However, the mechanisms regulating this normal variability are not completely understood. To test the hypothesis that the normal variability in fetal HR and blood pressure are produced by intrinsic fluctuations in sympathetic outflow, we recorded HR, mean arterial blood pressure (MABP), and renal sympathetic nerve activity (RSNA) in conscious, chronically instrumented, near-term fetal sheep (n= 5; 132–137 d of gestation, term being 145 d) and correlated the relationships between RSNA and MABP, and RSNA and HR. RSNA, HR, and MABP were sampled at a frequency of 4 Hz and the values averaged by 5-min blocks over a 4-h period. Linear regression analysis demonstrated a positive correlation between RSNA and both HR and MABP in all five fetuses (p< 0.02). In a second group of fetuses (n= 5), ganglionic blockade with trimethaphan (150–250 mg/kg/min) significantly attenuated (p< 0.05) the coefficients of variation of HR (12.3 ± 1.9%versus1.7 ± 0.6%) and MABP (5.8 ± 0.6%versus3.6 ± 0.5%). These results demonstrate that, in the fetus, fluctuations in HR and MABP are mediated by changes in sympathetic outflow and suggest an important role for the autonomic nervous system in fetal cardiovascular regulation. (Pediatr Res35: 250–254, 1994)

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

We hypothesized that during a critical neonatal period hyperoxia may produce alterations of sex-specific cytochrome P450 isozymes in adulthood (enzyme imprinting). To test this, newborn rats were exposed to 24 or 72 h of hyperoxia (O2> 95%) within 24 h after birth and killed at 120 d. In males, significant negative imprinting (decrease) was found in total cytochrome P450 content and male-specific CYP2C11 in the hyperoxia groups. Positive imprinting (increase) was noted in CYP1A2 and male-specific CYP3A2 in the 72-h hyperoxia group. These alterations were essentially similar when expressed on a per microsomal protein or per liver basis. In addition, the level of hepatic glucocorticoid receptor in adult male rats was elevated after neonatal hyperoxia. In females, there was a significant body and liver weight loss after hyperoxic exposure, which resulted in a negative imprinting of CYP1A2 and female-specific 2C12 in the 72-h hyperoxia group on a per liver basis, whereas the measured parameters were unaltered when expressed per microsome. In general, the changes were more marked with longer hyperoxic exposure, suggesting that more pronounced alterations may be induced with prolonged neonatal hyperoxia. Because hyperoxic exposure in premature neonates is a common clinical practice and decreased CYP2C11 in adult males is expected to result in feminization, we believe that the scope of this work should be expanded and eventually tested for its relevance in human subjects. (Pediatr Res35: 255–258, 1994)

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID