Old Guinea Pigs Research Articles

Heme oxygenase-1 regulates oxidant and antioxidant imbalance in guinea pigs with asthma

Objective To explor the antioxidant effects of heme oxygenase-1 （ HO-1 ） for asthma and its mechanism. Methods Thirty two months old healthy male guinea pigs were randomly assigned to 3 groups, all of them were feed under the same management condition. Asthmatic group, refering to Huston＇s research results, were sensitized by exposure to aerosolized ovalbumin（OVA） in order to build the guinea pig motile of asthma. Dexamethasone group （ DG）, were also sensitized by exposur to aerosolized ovalbumin as well as the asthraatic group had done and then treated with dexamethasone. Normal control group （NCG） ： were treated with 0. 9% sterile sodium chloride. All the tested animals were measured the activity of lung HO-1 ,levels of malondialdehyde （MDA） in the lung tissue or serum and bilirubin in the serum by spectro photometry. And the pathology and expression of HO-lprotein in the lung tissue were observed. Results In the OVA induced asthmatic group ,the HO-1 activity and level of MDA in lung tissue or serum were markedly increased compared with the groups of NCG and DG （ P 〈0. 01 ） and the expression of lung HO-1 protein was as 3-4 grade. While level of b＇llirubin was markedly reduced compared with NCG and DG. For example,in asthmatic group,the activity of lung HO-1 was,the level of bilirubin formed,（901.12 ＋321.53） pmol/（mg protein.h）. The level of MDA in senma was（ 12. 25 ＋2. 49） mmoL/ml. The level of lung MDA was（69. 38 ＋ 7. 49） nmol/mg protein,and the level of bilimbin in serum was （0. 54 ＋_0.23 ） pmol/L. In DG,the data of HO-1 and MDA as described above were markedly reduced compared with the OVA induced asthmatic group（P 〈0. 01 ） ,and lung pro- tein expression was 1-2 grade,while the level of bilirubin in the serum was increased（P 〈 0. 01 ）. But,all datas of DG had no significant difference compared with NCG （ P 〉 0. 05 ）. Conclusion The guinea pigs＇ in vivo lipid peroxide level increases and the level of bilirubin, an antioxidant, markedly decrease during asthma attacks, which induce the imbalance of oxidant and antioxidant. Content level and activity of HO-1 protein can in crease in asthma body in order to compensate the reduce of bilirubin level, regulate the imbalance of oxidant and antioxidant, protect lung tissues from oxidizing reaction damage and relieve allergy or asthma symptoms. Key words: Heme oxygenase-I ; Bilirubin; Asthma; Oxidation; Malondialdehyde; Guinea pigs

Myocardial Ca2+handling and cell-to-cell coupling, key factors in prevention of sudden cardiac deathThis article is one of a selection of papers published in a special issue on Advances in Cardiovascular Research.

Using whole-heart preparations, we tested our hypothesis that Ca(2+) handling is closely related to cell-to-cell coupling at the gap junctions and that both are critical for the development and particularly the termination of ventricular fibrillation (VF) and hence the prevention of sudden arrhythmic death. Intracellular free calcium concentration ([Ca(2+)](i)), ECG, and left ventricular pressure were continuously monitored in isolated guinea pig hearts before and during development of low K(+)-induced sustained VF and during its conversion into sinus rhythm facilitated by stobadine. We also examined myocardial ultrastructure to detect cell-to-cell coupling alterations. We demonstrated that VF occurrence was preceded by a 55.9% +/- 6.2% increase in diastolic [Ca(2+)](i), which was associated with subcellular alterations indicating Ca(2+) overload of the cardiomyocytes and disorders in coupling among the cells. Moreover, VF itself further increased [Ca(2+)](i) by 58.2% +/- 3.4% and deteriorated subcellular and cell-to-cell coupling abnormalities that were heterogeneously distributed throughout the myocardium. In contrast, termination of VF and its conversion into sinus rhythm was marked by restoration of basal [Ca(2+)](i), resulting in recovery of intercellular coupling linked with synchronous contraction. Furthermore, we have shown that hearts exhibiting lower SERCA2a (sarcoplasmic reticulum Ca(2+)-ATPase) activity and abnormal intercellular coupling (as in older guinea pigs) are more prone to develop Ca(2+) overload associated with cell-to-cell uncoupling than hearts with higher SERCA2a activity (as in young guinea pigs). Consequently, young animals are better able to terminate VF spontaneously. These findings indicate the crucial role of Ca(2+) handling in relation to cell-to-cell coupling in both the occurrence and termination of malignant arrhythmia.

Aminophylline alters the core temperature response to acute hypoxemia in newborn and older guinea pigs.

In newborns and adults of a number of species, exposure to acute hypoxemia produces a "regulated" decrease in core temperature, the mechanism of which is unknown. The present experiments were carried out on chronically instrumented newborn (5-10 days of age; n = 27) and older (25-30 days of age; n = 23) guinea pigs to test the hypothesis that adenosine mediates this regulated decrease in core temperature. During an experiment, core temperature was measured by biotelemetry from animals studied in a thermocline during a control period of normoxemia, an experimental period of normoxemia or acute hypoxemia (fraction of inspired oxygen 0.10), and during a recovery period of normoxemia after an intraperitoneal injection of 10 mg/kg aminophylline (i.e., a nonspecific adenosine antagonist) or vehicle. Core temperature decreased significantly during hypoxemia after vehicle in both newborn and older guinea pigs. After aminophylline, however, newborn guinea pigs failed to significantly decrease their core temperature, whereas older guinea pigs exhibited an attenuated yet significant core temperature decrease during hypoxemia. Our data support the hypothesis that adenosine plays an age-dependent role in mediating the regulated decrease in core temperature that occurs in newborn and older guinea pigs during acute hypoxemia.

Naloxone does not alter the "regulated" decrease in core temperature during hypoxemia in guinea pigs.

In newborns and adults of a number of species, exposure to acute hypoxemia produces a "regulated" decrease in core temperature, the mechanism of which is unknown. The present experiments were carried out in chronically instrumented newborn (5-10 days of age; n = 59) and older (25-30 days of age; n = 61) guinea pigs to test the hypothesis that the endogenous opioids mediate this regulated decrease in core temperature. During an experiment, core temperature, oxygen consumption, and selected ambient temperature were measured in a thermocline (linear temperature gradient of 10-40 degreesC) during a control period of normoxemia, an experimental period of normoxemia or hypoxemia (inspired oxygen fraction 0.10), and during a recovery period of normoxemia following an intraperitoneal injection of naloxone hydrochloride (a nonspecific opioid antagonist; 1, 2, or 4 mg/kg) or vehicle. Naloxone did not significantly alter basal core temperature or the core temperature response to acute hypoxemia in newborn or older guinea pigs. Naloxone did, however, decrease basal oxygen consumption in newborn and older guinea pigs and altered the thermoregulatory effector mechanism used to decrease core temperature during hypoxemia in the newborn guinea pigs. Our data do not support the hypothesis that the endogenous opioids mediate the regulated decrease in core temperature that occurs in newborn and older guinea pigs during exposure to acute hypoxemia.

Developmental differences in renal sulfate reabsorption: transport kinetics in brush border membrane vesicles.

Renal tubular reabsorption of inorganic sulfate is greater in younger than older guinea pigs. To determine the mechanism of this difference, we studied the transport of inorganic sulfate in renal brush border membrane vesicles (BBMV) obtained from young (< 25 days) and adult guinea pigs (> 60 days). BBMV were obtained by mechanical and osmotic disruption of dissected renal cortices followed by magnesium precipitation and differential centrifugation. After the membranes were incubated for 10 s in solutions containing inorganic sulfate at several concentrations (0.1-10 mM) and trace amounts of 35sulfate, intravesicular uptake was measured. Based on 35sulfur uptake, reabsorption transport kinetics (Vmax and Km) were estimated. BBMV obtained from young guinea pigs demonstrated higher sodium-sulfate cotransport, Vmax (51.79 +/- 4.34 pmol/mg protein per s) than those obtained from adult animals (Vmax = 34.28 +/- 9.17 pmol/mg per s), P < 0.05. Vmax values are represented as means plus or minus standard deviation. No differences in Km were observed. Our results indicate that age-related differences in renal inorganic sulfate reabsorption are due to a higher Vmax for sodium-sulfate cotransport in the younger animals, suggesting a higher density of sodium-sulfate cotransporters or an increased cotransport turnover rate in this age group.

Effects of aging on α 2-adrenoceptor mechanisms in isolated guinea-pig tracheal preparations

The effects of aging on α 2-adrenoceptor mechanisms in tracheal preparations isolated from 3-, 6-, 10-, 40- and 100-week-old guinea-pigs were studied. The potency of noradrenaline decreased with age. The specific binding of [ 3H]p-aminoclonidine to microsomal fractions prepared from tracheal smooth muscles from 6- and 40-week-old guinea-pigs was analysed by Scatchard analysis. The capacity of maximum binding sites of [ 3H]p-aminoclonidine was greater in the preparations from 40-week-old guinea-pigs than in 6-week-old animals, whereas the dissociation constant did not change with age. The amount of prostaglandin F 2α released by noradrenaline and the contractile response to prostaglandin F 2α decreased with age. These results suggest that an age-related decrease in the potency of noradrenaline is due to the decrease in the amount of excitable prostaglandin F 2α released by noradrenaline and in the contractile response to prostaglandin F 2α, but not to a change in the total number of α 2-adrenoceptors or in the dissociation constant of a drug from α 2-adrenoceptors. Extraneuronal uptake also plays a role in the response to noradrenaline in the tracheal preparations from older guinea-pigs.

Age-related changes in gallbladder contractility and gallbladder cholecystokinin receptor population in the guinea pig

We have examined the effects of aging on guinea pig biliary motility both in vitro and in vivo. The first experiment compared contractile tension of gallbladder strips from young adult (6–12 months old) and 3-year-old guinea pigs in vitro. Contraction of gallbladder strips from the young guinea pigs was twice as forceful and was more sensitive to octapeptide of cholecystokinin (CCK-8) stimulation than the gallbladder strips from the older guinea pigs. The two groups were also studied in vivo by measuring changes in the intraluminal pressure of the gallbladder in response to exogenously administered doses of CCK-8. Young adult guinea pigs were more sensitive to CCK-8 at the lower doses tested and demonstrated gallbladder constractions that were more forceful than that of the old guinea pigs. CCK receptors were measured on gallbladder muscularis membranes from young adult and old guinea pigs. The number of receptors on gallbladder membranes decreased with age: 65.0±17.7 fmoles/mg protein on membranes from 1 year old; 7.9±2.0 fmoles/mg protein on membranes from 3 years old. The binding affinity of CCK receptors on gallbladder muscularis membranes for binding to CCK-8 was not significantly different in the two age groups studied. We conclude that age-related decreases in gallbladder responses to CCK-8 may be due to decreased concentrations of CCK receptors on gallbladder muscle cells.

Effect of host age on the expression of acquired resistance to ticks.

Young guinea-pigs (350 g) expressed significantly greater levels of acquired resistance to challenge by larval Amblyomma americanum ticks than older guinea-pigs (520-800 g). This finding suggests that younger guinea-pigs are immunologically more responsive to tick infestation than older mature individuals. Therefore, host age is an important variable in evaluating acquired resistance to ticks.

The influence of sex and age on the deposition of L-xyloascorbic acid in tissues of guinea-pigs.

1. Young male and female guinea-pigs of similar age and male guinea-pigs of various ages were given daily oral supplements of vitamin C (L-xyloascorbic acid) (AA) on a body-weight basis for periods of 10–15 d and the resulting concentration of AA in several organs was determined.2. There was no difference between the sexes in the concentrations of AA in the adrenal glands and spleen. The concentration of AA in the spleen, adrenal glands and eye lens was significantly lower in older animals, and in brain it was significantly higher than the corresponding values for the young guinea-pigs.3. The tissue deposition after oral administration of AA for 10 d was compared with that resulting from intramuscular injection of the same quantity of AA over 10 d in males aged 60 d, males aged 500 d and females aged 500 d. In the 60-d-old guinea-pigs intramuscular injection raised the concentration of AA in the spleen and adrenal glands 35% and 50% respectively above that resulting from oral dosing. In the older guinea-pigs (500 d) the corresponding values were 108% and 127% respectively. It is concluded that reduced gastrointestinal absorption is, at least in part, responsible for the low AA concentrations in certain organs from older guinea-pigs. In the 500-d-old guinea-pigs there was no significant difference between the AA levels in the spleen, adrenals and brain of the two sexes, but AA level in the lens of females was significantly lower than that in males, irrespective of the mode of administration of the AA.

THE MEDIAN LETHAL DOSE (LD50) OF PENTOTHAL SODIUM FOR BOTH YOUNG AND OLD GUINEA PIGS AND RATS

THE MEDIAN LETHAL DOSE (LD50) OF PENTOTHAL SODIUM FOR BOTH YOUNG AND OLD GUINEA PIGS AND RATS