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Biomedical subjects

C M Tipton

Publications and source records attributed to C M Tipton.

At least 73 records · Page 4Linked to original sources

Voluntary exercise and its effects on young SHR and stroke-prone hypertensive rats.

To determine whether voluntary exercise would lower resting blood pressure in spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SP-SHR), two separate but interrelated investigations were undertaken. The studies were initiated when the animals were 28-35 days of age and after they were assigned to either activity or sedentary cages. The activity cages were connected to transducers and recorders that allowed the monitoring and calculation of frequency, duration, and running speed. The SHR group ran 3-7 km/day intermittently for 12 wk at high speeds (48-68 m/min), which resulted in heart rates in excess of 500 beats/min. When the SHR exercised, they seldom exceeded 33 revolutions/bout (37 m) with the majority being less than 22 revolutions/bout. This type of exercise training significantly lowered, but did not normalize, resting blood pressure by approximately 20 mmHg [nontrained (NT) = 185 +/- 5; trained (T) = 163 +/- 5 mmHg] while increasing maximum O2 consumption (VO2max) (NT = 78 +/- 2.6; T = 95 +/- 2.2 ml X min-1 X kg-1) and endurance run time (NT = 62 +/- 9.0; T = 286 +/- 15.0 min), respectively. Although SP-SHR exhibited comparable patterns of voluntary activity, the effects were not similar. First, after approximately 5 wk of consuming a special Japanese rat chow and a 1% NaCl drinking solution, cerebrovascular lesions occurred and deaths ultimately resulted in both exercising and sedentary groups. Second, although there was statistical evidence for a training effect (higher VO2max, longer VO2 test run times), voluntary exercise had no advantage in either male or female runners in lowering resting blood pressures or in improving their life-spans. Whereas voluntary activity wheel exercise or moderate forced treadmill exercise will lower resting blood pressures in young SHR populations, similar generalizations cannot be made with young SP-SHR rats.

Animals↗

Determinants of VO2 max: insights gained from non-human species.

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.

Animals↗

Influence of exercise training on reactivity and contractility of arterial strips from hypertensive rats.

To determine whether the lowered resting blood pressure values in hypertensive rats were associated with changes in vascular reactivity and/or contractility, helical strips were obtained from different arteries from exercise-trained (running and swimming) hypertensive rats and from running normotensive rats. Each subgroup contained nontrained controls for comparison. Changes in muscle aerobic enzymes, maximum O2 consumption, and body weight indicated that a training effect had occurred. When norepinephrine was added in a dose-response manner to the testing chamber containing helical strips from either the descending aorta, femoral artery, or renal artery, there were no significant differences in reactivity (the negative log dose-response curve) attributable to the training of hypertensive or normotensive groups. However, the trained hypertensive rats exhibited a trend for lower contractility values (dyn/mm2) in some but not all of the strips tested. From these results, we concluded that the lowered resting blood pressures associated with exercise training of hypertensive rats could not be explained by changes in vascular reactivity of their arterial strips.

Animals↗

Exercise training and its effects with renal hypertensive rats.

The influence of endurance training on functional capacity [maximal O2 consumption (VO2 max)], caudal arterial blood pressure, and myocardial capillary density were investigated in normotensive rats and rats made hypertensive using the two-kidney one-clip approach (Goldblatt's hypertension). Male Sprague-Dawley rats were assigned to sham (N: 120-140 mmHg), moderately hypertensive (MH = 0.30-mm clips, 150-170 mmHg), or severely hypertensive (SH = 0.25-mm clips, 190-230 mmHg) groups. Rats designated to be runners (T) were exercised on a motor-driven treadmill equal to 50-70% of their VO2 max values for 8-12 wk. Compared with their nontrained (NT) controls, training was associated with significantly higher VO2 max values (12-15%) and muscle cytochrome-c oxidase activities (33-78%). Resting systolic blood pressure was not significantly changed in the N-and MH-T subgroups; however, it was 20-30 mmHg higher in the SH-T subgroup. Mean absolute heart weight for only the N-T group was significantly heavier than their NT controls. However, the mean predicted heart weights (heart wt = 0.639 X body wt of N-NT + 0.001 g) of the two SH groups were significantly higher than expected. The SH-T group had a lower (11%) subepicardial capillary density mean than its NT control and significantly fewer capillaries in the subendocardial region than the other five subgroups. It was concluded that moderate exercise training appeared to be detrimental to rats with severe hypertension because it increased resting blood pressure and decreased myocardial capillary density, even though it improved their functioning capacity.

Animals↗

Lower body negative pressure in the tranquilized rat.

The application of lower body negative pressure (LBNP) to tranquilized rats was assessed as an experimental technique to evaluate the response of the cardiovascular system to hypotension. After pilot studies had demonstrated that diazepam (600 micrograms X kg-1, i.v.) had no significant influence on the pressor response to unilateral carotid occlusion in unanesthetized and unrestrained rats, subsequent rats were tranquilized. When LBNP was applied, the decline in central venous pressure was linearly related to the level of negative pressure as was the initial fall in mean arterial pressure (MAP). Pulse-interval was highly correlated with the initial fall of MAP. The results indicate that the application of LBNP in the tranquilized rat can effectively produce systemic hypotension and elicit cardiovascular reflexes similar to those reported for other animals in response to LBNP, including humans.

Animals↗

Responses of SHR to combinations of chemical sympathectomy, adrenal demedullation, and training.

The single and combined influences of exercise training, chemical sympathectomy (SYMX), and surgical adrenal demedullation (D) were examined in four separate spontaneously hypertensive rat (SHR) groups. SYMX was accomplished by subcutaneous injections of antinerve growth factor (ANGF) over a 5-day period after birth followed by 20 separate injections of guanethidine sulfate during a 27-day period. Measurements of urine, plasma, or tissue levels of catecholamines indicated that these experimental procedures were effective. The animals were exercise trained (T) for 10 wk or longer at 40-60% of their VO2max capacity, and all T groups exhibited longer run times or higher muscle cytochrome oxidase activity; however, only the SHR + T subgroup had a significantly higher VO2max value than its control (NT). Training lowered resting systolic blood pressure (SBP) in the SHR subgroup but normalization of SBP occurred only with SYMX. Interestingly, only the SYMX + T subgroup with intact adrenal glands also had lower SBP values than the NT. The SHR + T and SYMX + T subgroups but not the SYMX + D + T had less cardiac acceleration after ip injections of atropine than their controls. Heavier heart weights were observed only in the SHR + T subgroup; SYMX was associated with lighter heart weights regardless of whether the rats had been T or D. These collective findings demonstrated again the importance of the sympathetic nervous system to an exercise response, suggesting that an intact adrenal medulla was essential for SHR groups to achieve many of the adaptations associated with training.

Adrenal Medulla↗

Acute cardiorespiratory responses of hypertensive rats to swimming and treadmill exercise.

The acute cardiorespiratory responses of spontaneously hypertensive rats (SHR) to swimming and running exercise was investigated because SHR populations are hyperresponsive to external stimuli, of the paucity of existing data, and of the uncertainty on the role of exercise stimuli for training adaptations to occur. Male rats were assigned to one of five groups (n = 5-6/group) and designated as controls (C), inexperienced or naive free swimmers (NFS), experienced free swimmers (FS), experienced weighted swimmers (WS) (attached weights equal to 2% of their body weight) or experienced runners (R) who ran at an intensity of 75% of their VO2max. After 75 min in the water, all groups were acidotic and hypercapnic with the WS experiencing the greatest changes. Heart rate (HR) was increased in all swimmers during the initial 10 min, but declined thereafter, and after 75 min, the HR of WS (348 +/- 1 beats/min) was significantly lower than the C group (416 +/- 22 beats/min). At the same time interval, mean arterial blood pressure (MAP) was decreased in all swimming groups to values lower than the C animals. In addition, an exaggerated diving reflex was frequently noted when the rats were submerged. When the magnitudes of the changes were evaluated in the swimming animals they were directly associated with their submergence times, i.e., during 65-75 min of the swim, NFS, FS, and WS were submerged for 43, 46, and 66% of their total swim time, respectively. In sharp contrast to the swimmers, the runners exhibited increases in HR and MAP with their blood gas measurements being indicative of hyperventilation. We concluded that swimming as an exercise mode for hypertensive rats is best served to study the combined effects of excitement, prolonged submergence, and the consequences of the diving reflex.

Animals↗

Fluid shifts and muscle function in humans during acute simulated weightlessness.

Head-down tilt is considered an effective experimental model to simulate weightlessness. To determine the acute effects of simulated weightlessness on transcapillary fluid balance, tissue fluid shifts, muscle function, and triceps surae reflex time, eight supine subjects were tilted 5 degrees head down for 8 h. A cephalic fluid shift from the legs was indicated by facial edema, nasal congestion, increased urine flow, decreased creatinine excretion, reduced calf girth, and decreased lower leg volume. As measured by wick catheters inserted under local anesthesia, interstitial fluid pressure in the tibialis anterior muscle (4.6 +/- 0.6 mmHg) and subcutaneous tissue (0.6 +/- 0.5 mmHg) of the lower leg fell significantly to -2.8 +/- 0.5 and -3.8 +/- 0.4 mmHg, respectively. Other transcapillary pressures (capillary and interstitial fluid colloid osmotic pressures) were relatively unchanged. Needle-biopsy specimens, obtained just before and after tilt, indicated that total water content of soleus muscle was unchanged during 8 h of head-down tilt. After head-down tilt, isometric strength and isokinetic strength of the plantar flexors were unchanged. Triceps surae reflex time associated with plantar flexion movement slowed slightly after the tilt maneuver. Collectively these results demonstrated a dehydration effect of head-down tilt on muscle and subcutaneous tissues of the lower leg that may affect muscle function.

Adult↗

Influences of exercise intensity, age, and medication on resting systolic blood pressure of SHR populations.

The influence of exercise training on the resting caudal arterial blood pressures (RBP) of hypertensive rats is unclear despite numerous investigations by different investigators. To determine whether RBP values were influenced by the intensity and the initial age of the animal at the time of training, several studies were undertaken that involved more than 100 rats. When male and female rats were endurance trained for 24 wk at an O2 consumption in excess of 75% of their maximum (Vo2 max), RBP results from nontrained (NT) or trained (T) animals were not significantly different even though at several time periods the T animals had higher resting pressures. However, when exercising rats at an intensity level representing 40-60% of their Vo2 max, the T groups had consistently lower RBP than their NT controls during the majority of the experimental time periods. In addition exercising young (2-3 wk old) hypertensive-prone rats at a moderate intensity was associated with lower RBP within 4-6 wk after the initiation of training; however, exercise training could not normalize RBP. Reduced dosages (85% of normal) of antihypertensive medication, when combined with moderate training, was also associated with lower and "normal" RBP in male but not female rats. We conclude that moderate exercise at an early age when combined with subnormal dosages of antihypertensive medication holds promise for the normalization of RBP in male hypertensive rats of a genetic origin.

Aging↗

Considerations for exercise prescriptions in future space flights.

The launching of the shuttle in 1981 initiated a new era in the space age. In spite of the more than 20 yr of experience and research on the anatomical and physiological effects of weightlessness, problems remain. The resolution of these problems requires countermeasures, of which exercise deserves to be considered. The uncertainty concerning the importance of exercise has evolved, in part, because of the limited number of subjects studied, the paucity of controlled experimental designs, the inability to follow standardized routines in a space environment, and the lack of specificity in the exercises prescribed. Exercise has the potential to be an effective countermeasure for the decreases in bone density, fluid volumes, muscle mass, muscular strength, orthostatic tolerance, cardiovascular deconditioning, and submaximal exercise performances that occur in a O-gravity environment if aerobic training is minimized, maximum isometric and power-type exercises are emphasized, and circuit-training principles utilized. Because the majority of future space flights will last 21 d or less, the majority of future studies on the role of exercise should concentrate on that time period.

Blood Volume↗

An in situ study of the influence of a sclerosing solution in rabbit medial collateral ligaments and its junction strength.

A double-blind study was conducted to assess the influence of a sclerosing solution on rabbit medial collateral ligaments (MCL) in situ. It was shown that repeated injections of 5% sodium morrhuate into the MCL and its bony attachments significantly increased its bone-ligament-bone junction strength, ligament mass and thickness when compared to saline-injected controls. Morphometric analysis of electron micrographs showed a highly significant corresponding increase of the collagen fibril diameters in the experimental ligament compared against the control MCL. These composite findings suggested that the sclerosing solution had a significant influence on dense connective tissue at the insertion sites. The mechanisms for these changes are uncertain and are the basis for future investigations.

Animals↗

Metabolic and cardiovascular adaptations in trained hypophysectomized rats.

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.

Adaptation, Physiological↗

Influence of training on the blood pressure changes during lower body negative pressure in rats.

The responses of non-trained and endurance-trained rats to conditions of lower body negative pressure (LBNP) was evaluated in normotensive, borderline hypertensive, and genetic hypertensive groups, as well as in sub-groups subjected to conditions of ventilation with 100% oxygen, systematic hemorrhaging, or sino-aortic denervations. Compared to their non-trained controls, normotensive trained rats exhibited significantly greater and faster falls in arterial blood pressure. This finding suggested a change in baroreceptor sensitivity. Related, but not statistically significant trends were observed with the hypertensive groups. Borderline hypertensive rats (DOCA injections) did not demonstrate any of these differences. Measurements of blood changes during the LBNP procedure and the effects of inspiring 100% oxygen indicated that the aortic and carotid chemoreceptors were not responsible for this training effect. After baroreceptor denervation, the group differences were abolished. In addition, the training effects were generally absent when hemorrhaging was performed, a result suggesting a difference in compliance. We have concluded from these results that endurance training will be associated with greater decreases in arterial blood pressure during LBNP than will be experienced by non-trained populations. However, the responsible mechanisms are unclear and will require further investigation.

Animals↗

Knee-ligament loading properties as influenced by gravity: I. Junction with bone of 3-G rodents.

After chronic 3-G centrifugation of rats, their bone-to-ligament junctions exhibited 95 +/- 12% of the control junctions' force-sustaining capacity (F). F was actually 29 +/- 5% greater for centrifuged rats than for control rats of comparable size, as experimental animals grew to smaller body mass. This suggests that gravity determines part of F's magnitude. These junctions are, therefore, hypothesized to be weaker after development in a weightless environment. The effect was less measurable for mice. F was measured in situ as load needed to separate the knee's medial collateral ligament from the tibia of 34 male rats (Sprague-Dawley, 27-320 d of age, exposed 4-65 d), 30 control rats, 22 male mice (Swiss Webster, 35-166 d, exposed 9-56 d), and 15 control mice.

Age Factors↗