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The primary purpose of this investigation was to secure select anatomical and physiological measurements from hypophysectomized rats and their sham-operated control to determine how various endocrine influences could be modified by conditions of simulated microgravity. The focal point of the study was the exercise responses after head-down suspension; however, we were also interested in obtaining insights on nonexercise-related mechanisms. Since more details and information concerning this study will be published elsewhere, we will highlight those findings which warrant further research.

Head-down suspension (HDS) of rats has evolved as a useful model for the simulation of a microgravity environment. Previous HDS experiments with rats have shown an impaired capacity to perform aerobic exercise as demonstrated by reductions in maximum oxygen consumption (VO2 max), treadmill run time (RT), and mechanical efficiency (ME) of treadmill running at submaximal conditions. To determine whether endurance training (TR) before HDS would modify exercise performance, male Sprague-Dawley rats were assigned to nontrained (NT) or TR groups for 6 wk and exposed to HDS or cage control (CC) conditions for 29 days. The rats were tested for VO2 max, RT, and ME before treatment and on days 7, 14, 21, and 28. In addition, water and electrolyte excretion was measured on days 1 and 21 of the experimental period. Before HDS, the TR rats had significantly higher measures of VO2 max (15%) and RT (22%) than the NT rats. On day 28, HDS was associated with significant reductions in absolute VO2 max (ml/min) in TR (-30%) and NT (-14%) rats. Relative VO2 max (ml.min-1.kg-1) was significantly reduced in TR (-15%) but not NT rats. Similar reductions in RT occurred in TR (-37%) and NT (-35%) rats by day 28. ME was reduced 22% in both TR and NT rats after 28 days of suspension. HDS elicited diuresis, natriuresis, and kaliuresis in TR rats after 21 days but not after 24 h. In contrast, HDS-NT rats exhibited no diuretic, natriuretic, or kaliuretic responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Results from previous studies have shown that the reduction in maximal oxygen consumption (VO2max) with simulated microgravity is attenuated in chemically sympathectomized rats. To determine the contributions of the catecholamines from the adrenal medulla in this process, investigations were conducted with 65 saline injected (SAL) and chemically sympathectomized (SX) female rats that were either surgically demedullated (DM), or intact (IN). Microgravity conditions were simulated by head-down suspension (HDS) while controls were assigned to individual cages (CC). The experimental period was 14 d. The rats were tested for VO2max, treadmill run time (RT), and submaximal mechanical efficiency (ME) prior to suspension and on days 7 and 14. Saline injected rats that had intact adrenal medullas (SAL-IN) exhibited significantly reduced measures of VO2max after 7 and 14 d by 15% and 21%, respectively. No significant reduction in VO2max was observed with HDS in the SX-IN animals. Sympathectomized rats that were demedullated (SX-DM) also exhibited a significant reduction in VO2max (12%). In addition, HDS was associated with a marked and significant reduction in RT in all groups. ME for submaximal exercise was significantly reduced after HDS in SAL-IN rats but not in the SX-IN rats. SX-DM rats experienced significant reductions in ME similar in magnitude to the SAL-IN rats. These results confirm that chemical sympathectomy attenuates the expected decrease in VO2max with HDS and suggests that circulating epinephrine contributes to this response.

To determine the time course of changes in maximal oxygen consumption (VO2max) and its relationships with body composition, a 29-d simulated microgravity study was initiated with 30 adult female rats (230-280 g) randomly assigned to one of three experimental groups; namely, head-down suspension (HDS) at 45 degrees, horizontal suspension (HS) at 0 degree, or cage control (CC). Five separate exercise performance tests with measurements related to VO2max, treadmill run time, and mechanical efficiency were conducted before suspension and on days 7, 14, 21, and 28. The animals were sacrificed and chemically analyzed for fat and fat-free free mass (FFM) between days 22 and 29. When oxygen consumption results were expressed on an absolute basis (ml.min-1), both suspension groups had significant decreases at day 7. Thereafter, the HDS rats remained significantly decreased, while the HS rats returned to values not significantly different than the presuspension values by day 28. When oxygen consumption was expressed on a relative basis (ml.kg-1.min-1), all groups exhibited significant reductions between 6-8%. Both suspended groups had significantly less fat than the CC rats but had similar values for FFM (p greater than 0.05). When VO2max was evaluated on a FFM basis, the HDS rats had a group mean that was 6% lower than the other two groups, but the difference was not statistically significant. Treadmill run time was significantly reduced in all groups after 28 d with the reduction from pre-suspension values being more pronounced with HDS animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Male rodents were studied before and after undergoing one of three treatment conditions for 9 days: 1) cage control (n = 15, CON), 2) horizontal suspension (n = 15, HOZ), and 3) head-down suspension (n = 18, HDT). Testing included measurements of maximal O2 uptake (VO2 max) and select cardiovascular responses to graded treadmill exercise. VO2 max expressed on an absolute basis (ml/min) was significantly decreased after HOZ (-14.1 +/- 2.5%) and HDT (-14.3 +/- 2.0%), while being essentially unchanged in CON (-1.0 +/- 3.3%). Significant reductions in body weight were observed after both HOZ (-10.1 +/- 4.2 g) and HDT (-22.5 +/- 3.3 g), whereas CON animals exhibited a significant increase in weight (10.4 +/- 3.8 g). As a result, when VO2 max was normalized for body weight, all groups exhibited similar significant reductions of 6-7%. Although no differences in heart rate and blood pressure response to graded exercise were observed, the HDT group exhibited greater increases in mesenteric resistance at the same absolute exercise intensity. Furthermore, both suspended groups had higher iliac resistance values during exercise at similar relative exercise conditions, suggesting that muscle blood flow during treadmill running may have been reduced after suspension. In general, the decrements associated with the HOZ and HDT conditions were similar. It was concluded that reduction in exercise capacity and altered cardiovascular responses to exercise observed after 6-9 days of suspension were attributable to a combination of hypokinesia, lack of hindlimb weight bearing, or restraint, rather than to hydrostatic influences associated with HDT.

A ten-stage treadmill test was developed and standardized to secure the VO2max of male and female rats assigned to various cross-sectional and longitudinal experimental groups. Repeated measurements indicated that the test procedure was reliable and could be used for research purposes. When the test was used with different strains, the untrained Sprague-Dawley rats had significantly higher VO2max values than animals of the Wistar-Kyoto (WKY) or the Okamoto-Aoki (SHR) strains. Exercise schedules were evaluated that were similar to those previously used by various investigators and it was found that most were exercising their rats at levels exceeding 75% VO2max. After 6--10 wk of chronic exercise, significant increases in VO2max occurred that ranged between 12 and 26%. Longitudinal studies (1 yr) with hypertensive (SHR) rats revealed that it was more desirable to logarithmically evaluate the relationship between VO2max and body mass than by the conventional method of ml . kg-1 . min-1. When this approach was used with SHR animals, the VO2max differences between the sexes were not apparent until the animals were 1 yr of age. On the other hand, training by male SHR rats caused significant increases in VO2max regardless of the method used to express the results. It is recommended that future studies designed to elucidate exercise mechanisms in rats should include a standardized VO2max test.

Traditionally, ligaments and tendons (L and T) have been regarded as metabolically inert structures. However, sufficient biochemical evidence on the metabolism of collagen has indicated that such a concept is no longer tenable. To determine whether L and T respond to increased or decreased levels of chronic exercise, studies were undertaken to measure their aerobic capacities. For comparative purposes, similar measurements were obtained from liver and skeletal muscles secured from normal and hypophysectomized male rats. Oxygen consumption and cytochrome oxidase (CO) activity was recorded from cell suspensions that had been prepared with the inclusion of collagenase and with elastase added to the medium. The O2 results showed that L and T had values that were approximately 10 times lower than liver tissue and 7.5 times less than the means from skeletal muscles. Hypophysectomy caused marked reductions in O2 uptake of liver and muscle tissues; but had no impact on L and T. When CO activity of these connective tissues were evaluated, immobilization and hypophysectomy caused significant reductions that ranged from -36% to -59% respectively. Training, on the other hand, resulted in increases of less than 10% in the activity of this enzyme within L and T while being elevated in muscle tissue by 58%. It was concluded that the metabolic activity of L and T was lowered with decreased levels of physical activity but it was unclear why chronic exercise did not produce the opposite effect.

Metabolic and cardiovascular changes resulting from acute and chronic exercise were examined in male Sprague-Dawley rats assigned to sham-control or hypophysectomized groups. Two weeks after surgery, the hypophysectomized rats had decreased their maximum oxygen consumption (VO2 max) and heart rate values by 4 ml X min-1 X kg-1 and 142 beats X min-1, respectively. Twenty weeks later, hypophysectomy was associated with a 22 ml X min-1 X kg-1 decrease in VO2 max and a 215 beat X min-1 decline in their maximal heart rates when compared with sham-control means. Endurance training was responsible for the significantly higher O2 consumption values. Additionally, trained animals exhibited longer run times, higher muscle cytochrome oxidase activity, and reduced food consumption. Measurements of right atrial choline acetyltransferase (CAT) activity and [3H]quinuclidinyl benzilate (QNB) binding revealed significantly higher CAT values and fewer muscarinic receptors. However, training had no significant effect on resting blood pressure, blood pressure changes with conditions of lower body negative pressure, muscle glycogen concentrations, CAT levels and QNB binding of the left atrium and ventricular regions, or receptor density. These results indicated that many of the adaptations that are characteristic of normal populations can occur in the absence of the hormones from the pituitary gland.

Male Sprague-Dawley rats were assigned to three groups designated as diabetic, diabetic-plus-insulin, and control and tested for maximum oxygen consumption (VO2max) and maximum heart rate on three different occasions during the 6- to 8-wk experimental period. Compared with the prediabetic values and the means of the other two groups, diabetic animals had significantly higher submaximum and lower maximum VO2 values. These relationships prevailed when the groups were evaluated in terms of ml.kg-1.min-1 or ml.(kg0.79-1).min-1. In addition, the diabetic animals had significantly lower submaximum and maximum heart rates and shorter run times. Daily injections of insulin (2 U.day-1.rat-1) restored VO2max to within the limits of the control animals but did not normalize heart rates or run-time values. The linear relationship between heart rates and VO2 was repeatedly demonstrated with normal animals. However, this relationship progressively declined with the time course of diabetes. These results indicate that, in untreated diabetes, functional capacity is markedly reduced with the progression of the disease and suggest that alterations in the autonomic nervous system, tissue metabolic capacity, and decreases in lean body mass are responsible for the changes noted.

Lars Hermansen's distinguished but prematurely ended career was associated with the measurement and interpretation of the functional capacities of a variety of populations which included elite performers. In assessing human performance, the ability to utilize oxygen has become the single most important parameter to exercise physiologist. Despite the number of experiments that have been conducted on oxygen consumption during the past decades, the responsible mechanisms continue to be debated and investigated. The increasing limitations being placed on human research encourages exercise scientists to use animals to investigate unresolved issues. Surprisingly, there is a dearth of experimental animal studies in which measurements of VO2max, cardiac output (Q) or a-vO2 differences have been made simultaneously. From the data available, it appears that the mongrel dog and the rat exhibit changes in Q, stroke volume and a-vO2 differences that are similar to those reported for humans. On the other hand, foxhounds would appear to be the animal of choice to study VO2max improvements associated with only changes in cardiac output. Because of the role of the spleen as a reservoir for erythrocytes, the horse would be the appropriate animal to investigate changes in VO2max that would be mediated by alterations in the oxygen content of the blood. Interestingly, cattle could be the animal of choice to study the relationships between cardiac contractility, Q, stroke volume and VO2max. Extensive investigations with rats have demonstrated that VO2max can be increased by endurance training in most animal models for disease or hormonal deficiencies. It is apparent from the literature that in the area of VO2max determinations and mechanisms, animal exercise physiologists have not progressed to the degree of sophistication exhibited by human exercise physiologists. However, it is predicted that by the next decade, this situation will no longer exist and human physiologists will utilize various animal models to advance their understanding of the VO2max changes with aging, training, disease or combinations thereof.