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S L Britton

Publications and source records attributed to S L Britton.

At least 19 recordsLinked to original sources
PubMed2006

Enhanced mitochondrial sensitivity to creatine in rats bred for high aerobic capacity.

Qualitative and quantitative measures of mitochondrial function were performed in rats selectively bred 15 generations for intrinsic aerobic high running capacity (HCR; n = 8) or low running capacity (LCR; n=8). As estimated from a speed-ramped treadmill exercise test to exhaustion (15 degrees slope; initial velocity of 10 m/min, increased 1 m/min every 2 min), HCR rats ran 10 times further (2,375+/-80 m) compared with LCR rats (238+/-12 m). Fiber bundles were obtained from the soleus and chemically permeabilized. Respiration was measured 1) in the absence of ADP, 2) in the presence of a submaximally stimulating concentration of ADP (0.1 mM ADP, with and without 20 mM creatine), and 3) in the presence of a maximally stimulating concentration of ADP (2 mM). Although non-ADP-stimulated and maximally ADP-stimulated rates of respiration were 13% higher in HCR compared with LCR, the difference was not statistically significant (P>0.05). Despite a similar rate of respiration in the presence of 0.1 mM ADP, HCR rats demonstrated a higher rate of respiration in the presence of 0.1 mM ADP+20 mM creatine (HCR 33% higher vs. LCR, P<0.05). Thus mitochondria from HCR rats exhibit enhanced mitochondrial sensitivity to creatine (i.e., the ability of creatine to decrease the Km for ADP). We propose that increased respiratory sensitivity to ADP in the presence of creatine can effectively increase muscle sensitivity to ADP during exercise (when creatine is increased) and may be, in part, a contributing factor for the increased running capacity in HCR rats.

Adenosine Diphosphate↗
PubMed2001

Cardiac performance in inbred rat genetic models of low and high running capacity.

1. Previous work demonstrating that DA inbred rats are superior to COP inbred rats in aerobic treadmill running capacity has indicated their utility as genetic models to explore this trait. We tested the general hypothesis that intermediate phenotypes of cardiac function and calcium metabolism are responsible for the difference in capacity between these strains. 2. Logical cardiac trait differences were estimated at a tissue (isolated papillary muscle), cellular (isolated left ventricular cells), and biochemical level of organization. 3. DA hearts were found to give significantly higher values than COP hearts for: (1) maximal developed tension (38.3 % greater), and rates of tension change in contraction (61 %) or relaxation (59 %) of isolated papillary muscle, (2) fractional shortening (50 %), amplitude of the Ca(2+) transient (78.6 %), and caffeine-induced release of Ca(2+) from the sarcoplasmic reticulum (SR; 260 %) in isolated ventricular myocytes, and (3) Na(+),K(+)-ATPase activity of isolated myocytes (17.3 %). 4. Our results suggest that these trait differences may prove useful for further studies into the genes responsible for natural variations in both ventricular function and aerobic endurance capacity. Understanding the genetic basis of aerobic capacity will help define the continuum between health and disease.

Animals↗
PubMed2001

Artificial selection for intrinsic aerobic endurance running capacity in rats.

Artificial selection for intrinsic aerobic endurance running capacity was started using genetically heterogeneous N:NIH stock of rats as a founder population (n = 168). Selection for low and high capacity was based upon distance run to exhaustion on a motorized treadmill using a velocity-ramped running protocol. The starting velocity was 10 m/min and was increased by 1 m/min every 2 min (slope was constant at 15 degrees ). At each generation, within-family selection was practiced using 13 families for both the low and high lines. A rotational breeding paradigm maintained the coefficient of inbreeding at less than 1% per generation. On average the founder population ran to exhaustion in 355 +/- 11 m. Six generations of selection produced lines that differed in running capacity by 171%, with most of the change occurring in the high line. At generation 6 the low line ran 310 +/- 8 m and the high line 839 +/- 21 m at exhaustion. Selection for running capacity produced changes in body weight as a correlated trait. By generation 6, the low-line females were 20% heavier than the high-line females, and the low-line males were 16% heavier than the high-line males.

Animals↗
PubMed2001

Animal genetic models for complex traits of physical capacity.

Animal genetic models for complex traits of physical capacity. Exerc. Sport Sci. Rev., Vol. 29, No. 1, pp 7-14, 2001. Understanding the genetic basis for variance in complex physical traits such as aerobic capacity has become an attainable goal. A starting point is the development or identification of animal genetic models that contrast the low and high values for the trait of interest. Genes that cause natural trait variation can ultimately be determined from animal models via genetic linkage.

Animals↗
PubMed2001

Cardiac function in rats selectively bred for low- and high-capacity running.

Rat genetic models of intrinsic (i.e., untrained) low-capacity runners (LCR) and high-capacity runners (HCR) are being developed by artificial selective breeding for treadmill running. At generation 3, these lines differed in running capacity by 114%. We used generation 3 rats to test the hypotheses that HCR, relative to LCR, have 1) greater isolated cardiac performance and 2) more resistance to myocardial ischemic insult. The LCR ran for 227 +/- 7 m, and the HCR ran 994 +/- 11 m at exhaustion (337% difference, P < 0.001). Isolated heart performance was assessed from cardiac output (CO) generated at constant preload (15 mmHg) and afterload (70 mmHg) using a Langendorff-Neely working heart preparation. CO averaged 33.5 +/- 2.0 ml. min(-1). g(-1) in LCR hearts and 49.9 +/- 1.4 ml. min(-1). g(-1) in HCR hearts (49% difference, P < 0.001). Recovery of CO after 25 min of global ischemia was not different between the lines. These results suggest that 1) increased cardiac performance accounts for part of the difference in running capacity between the lines; and 2) unlike exercise training, genetically determined intrinsic capacity for exercise does not influence the recovery from 25 min of global low-flow cardiac ischemia.

Animals↗
PubMed2000

A self-powered constant infusion device for use in unrestrained rats.

We developed a device that delivers fluid through a catheter at a constant rate and can be used in conscious animals to solve a variety of problems. For example, this device can be used for delivering drugs and maintaining intravascular catheter patency. The device provides infusions at low flows (1.0-1.5 ml/day), so that experimental agents may be administered with minimal volume loading of the rat. Arterial and venous catheter patency is maintained by infusion of heparinized saline through indwelling catheters attached to the device. The catheters exit from the rat in the intrascapular area and are routed through a protective spring to the device, which is suspended above the cage. The catheters may be attached to pressure transducers, blood may be sampled, and injections or infusions may be made without disturbing the rat. Because the device is self-contained, it can be suspended by a fluid-free swivel that rotates through 360 degrees, providing minimal restraint. The device has been used successfully to measure arterial and central venous blood pressures in two studies using rats.

Animals↗
PubMed1999

Phenotypic differences in cardiovascular regulation in inbred rat models of aerobic capacity.

The Dark Aouti (DA) inbred strain of rats has superior aerobic treadmill running capacity compared with the Copenhagen (COP) strain of inbred rats. This difference in aerobic capacity provides a model to explore the genetic basis of variation in this trait. The present study evaluated intermediate phenotypic differences between 10 male COP inbred rats and 10 male DA inbred rats that might contribute to the difference in aerobic capacity between the strains. Five autonomically regulated cardiovascular variables were evaluated during rest or exercise by measuring the response to autonomic antagonists. The DA rat had enhanced autonomic function for the regulation of peripheral blood flow and cardiac output. Specifically, at rest the DA rats had significantly more sympathetic (123 +/- 8 vs. 99 +/- 7 beats/min) and parasympathetic (35 +/- 5 vs. 12 +/- 3 beats/min) tonus for heart rate control and more sympathetic support of blood pressure (70 +/- 7 vs. 38 +/- 6 mmHg) compared with the COP rats. During three graded levels of treadmill exercise the DA rats had higher blood pressures (16% on average) and higher heart rates (4% on average) relative to the COP rats. In addition, the DA rats had a 27% greater heart weight-to-body weight ratio compared with the COP strain of rats (3.63 +/- 0.08 vs. 2.85 +/- 0.07 g/kg). All five of these intermediate phenotypes could participate as variables causative of the difference in treadmill running capacity between the DA and COP strains of rats.

Animals↗
PubMed1999

A gravimetric method for the measurement of total spontaneous activity in rats.

Currently available methods for the measurement of spontaneous activity of laboratory animals require expensive, specialized equipment and may not be suitable for use in low light conditions with nocturnal species. We developed a gravimetric method that uses common laboratory equipment to quantify the total spontaneous activity of rats and is suitable for use in the dark. The rat in its home cage is placed on a top-loading electronic balance interfaced to a computer. Movements are recorded by the balance as changes in weight and transmitted to the computer at 10 Hz. Data are analyzed on-line to derive the absolute value of the difference in weight between consecutive samples, and the one-second average of the absolute values is calculated. The averages are written to file for off-line analysis and summed over the desired observation period to provide a measure of total spontaneous activity. The results of in vitro experiments demonstrated that: 1) recorded weight changes were not influenced by position of the weight on the bottom of the cage, 2) values recorded from a series of weight changes were not significantly different from the calculated values, 3) the constantly decreasing force exerted by a swinging pendulum placed on the balance was accurately recorded, 4) the measurement of activity was not influenced by the evaporation of a fluid such as urine, and 5) the method can detect differences in the activity of sleeping and waking rats over a 10-min period, as well as during 4-hr intervals recorded during active (night-time) and inactive (daytime) periods. These results demonstrate that this method provides an inexpensive, accurate, and noninvasive method to quantitate the spontaneous activity of small animals.

Animals↗
PubMed1999

Phenotypic variation in sensorimotor performance among eleven inbred rat strains.

As a first step toward identifying the genes that determine sensorimotor ability (motor coordination) we subjected 11 inbred strains of rats to three different tests for this trait. Rats were tested at 13 wk of age to determine how long they could remain on 1) a rotating cylinder as the velocity of rotation increased every 5 s (1-direction rotation test), 2) a rotating cylinder that reversed direction every 5 s and increased velocity every 10 s (2-direction rotation test), and 3) a platform that was tilted 2 degrees every 5 s from 22 to 47 degrees (tilt test). On all three tests, rats of the PVG strain demonstrated the greatest sensorimotor ability. In contrast, rats of the MNS strain were most often represented among the group of strains that demonstrated the lowest performance on all tests. Considering all three tests, there was a 3- to 13-fold range in sensorimotor performance between the highest and lowest strains. This large divergence between the highest and lowest strains provides a genetic model that can be used to identify intermediate phenotypes and quantitative trait loci that contribute to sensorimotor ability.

Animals↗
PubMed1999

Body fluid expansion is not essential for salt-induced hypertension in SS/Jr rats.

To evaluate the importance of volume in the development of hypertension in inbred Dahl salt-sensitive rats (SS/Jr), we measured the changes in blood pressure (BP) that occurred with oral intake of food (salt) and water in rats whose body weight was permitted to increase versus those in which body weight was maintained constant with a servo-control system. We hypothesized that if volume expansion is essential in the development of hypertension, then BP would not increase if body weight was held constant. We found that oral presentation of chow containing 4% salt to SS/Jr rats caused BP to increase 32.2 +/- 2.9 mmHg over 4 days when body weight was controlled at its initial value. Plasma sodium increased from 142.0 to 145.2 meq/l during 4 days of high salt. Neither plasma volume, hematocrit, nor central venous pressure changed significantly on the high-salt diet. In contrast, the inbred Dahl salt-resistant rats (SR/Jr) did not increase their BP during body weight control when given 4% salt. This demonstrates that volume expansion is not an obligatory step in the pressure response to increased salt in SS/Jr rats. Our results obtained with oral presentation of salt, in contrast to intravenous, represent a physiological evaluation of the significance of volume changes in response to dietary salt because no potential regulatory reflexes have been bypassed.

Animals↗
PubMed1998

Heritability of treadmill running endurance in rats.

Treadmill running was evaluated as a phenotype for selective breeding for high- and low-endurance performance from a starting population of 18 male and 24 female outbred Sprague-Dawley rats. Each rat was exercised to exhaustion once per day for 5 consecutive days. The treadmill was set at a constant 15 degrees slope, and the initial velocity of 10 m/min was increased by 1 m/min every 2 min. The total distance run on the single best day out of the five trials was taken as the measure of endurance performance. The original population (males and females combined, n = 42) ran on average for 396 m. The two lowest-performing pairs and two highest-performing pairs were selectively bred through three successive generations. After three generations of selection, performance of the offspring from the high selected line averaged 659 +/- 36 m (n = 20), whereas low-performance offspring (n = 13) averaged 388 +/- 28 m. The narrow-sense heritability, calculated as the regression of individual offspring performance on midparental value for each family, was 0.39 across the three generations. This implies that 39% of the variation in running endurance performance between the low and high selected lines was determined by heritable factors.

Animals↗
PubMed1998

Spectrum of aerobic endurance running performance in eleven inbred strains of rats.

The goal of this study was to identify inbred rat strains that could serve as useful models for exploration of the genetic basis of aerobic endurance performance. Six rats of each gender from 11 different inbred strains were tested for 1) maximal running capacity on a treadmill and 2) isolated cardiac performance. Running performance was estimated from 1) duration of the run, 2) distance run, and 3) vertical work performed. Cardiac output, during constant preload and afterload, was taken as a measure of cardiac performance from an isolated working heart preparation. The COP rats were the lowest performers and the DA rats were the best performers by all estimates of running performance. Across the 11 strains, the distance run correlated positively with isolated cardiac performance (r = 0.87). Estimates of performance were as follows (COP vs. DA strain, respectively): duration of run, 19.9 +/- 1.8 vs. 41.5 +/- 2. 2 min; distance run, 298 +/- 30 vs. 840 +/- 64 m; vertical work, 15 +/- 1.7 vs. 40 +/- 4.4 kg/m. These approximately 2.5-fold differences in running performance between the COP and DA suggest that these strains could serve as models for evaluation of the genetic basis of variance in aerobic performance.

Aerobiosis↗
PubMed1998

Phenotypic variation in strength among eleven inbred strains of rats.

As a first step toward the long-range goal of identifying the genes that determine strength, we subjected 11 inbred strains of rats to three tests of muscular strength. The tests consisted of measuring (1) the force exerted by the rat as it was pulled by the base of the tail off a grid on the pan of a top-loading electronic balance (scale test); (2) the length of time the rat hung from a 2.5-mm-diameter U-shaped wire (wire-hanging test); and (3) the length of time the rat hung from a vertically oriented grid consisting of 4-mm-diameter rods (grid-hanging test). Six rats of each gender from each strain were tested at 12 weeks of age, once/day for 5 consecutive days. For the two tests that required use of all four limbs (the scale and grid-hanging tests), one strain performed best (DA). In contrast, on the test that required primarily the use of the front limbs (wire-hanging test), the DA was the lowest performing strain and the F344 rats the best. This differential ranking suggests that the tests selected for variance in the morphological distribution of strength among the strains. There was a 1.5- to 5.2-fold divergence observed between the males of the highest and lowest strains on the scale test and grid hanging tests. This large divergence provides the opportunity to search for intermediate phenotypes and quantitative trait loci that contribute to the different performances of the strains on these strength tests.

Animals↗
PubMed1997

Evaluation of the renin-angiotensin system in a congenic renin Dahl salt-sensitive rat.

When an approximately 30 centiMorgan (cM) region of chromosome 13 containing the renin gene from the Dahl salt-resistant rat (R) was introgressed into the Dahl salt-sensitive rat (S), the resulting congenic rat (designated S.R-Ren) had a systolic blood pressure on a 2% (w/w) salt diet that was 24 mmHg lower than that of its S counterpart. Due to the large size of the transferred segment (over 30 million bp), the question remained as to whether or not the renin gene was the cause of the blood-pressure difference between the strains. We evaluated the role of the renin-angiotensin system in S.R-Ren and S rats fed a 0.05% salt diet by examining differences between strains in (1) expression of renin in three tissue types, (2) the blood-pressure response to blockade of both angiotensin-converting enzyme and angiotensin II receptors, and (3) pressure natriuresis. No differences were found in renin levels in plasma, kidney or adrenal gland between strains. The blood-pressure responses to the angiotensin-converting-enzyme inhibitor captopril and to the angiotensin II-receptor blocker saralasin in conscious S and S.R-Ren rats were similar. Furthermore, renal function, evaluated by a pressure-natriuresis index that took into account both the time and the arterial pressure needed to excrete an acute salt load, did not differ between strains. Our findings therefore fail to demonstrate a role for the renin gene in conferring lower blood pressure in the congenic rat and suggest that there is an unknown arterial-pressure-regulating locus in this 30 cM region of chromosome 13.

Adrenal Glands↗
PubMed1997

Hepatorenal reflex in the rat.

The possible existence of a hepatorenal reflex was evaluated in male Sprague-Dawley rats. Sodium excretion was measured in two groups of six rats each, during the first 4 h following acute ingestion of a known amount of high salt chow (2.0-2.5 mequiv. NaCl). Hourly excretion rates for sodium before surgery were compared with results following 7 days of recovery from either hepatic denervation (n = 6) or sham denervation (n = 6). Before denervation, hourly sodium excretion between the groups was not different. Following surgery for hepatic denervation, sodium excretion was 91% lower than presurgery values for the 1st h (p < 0.02) and 44% lower in the 2nd h (p < 0.04). Sham denervation caused no significant change in sodium excretion when compared with presurgery results. A test for completeness of denervation showed that norepinephrine concentration in liver tissue taken from denervated rats was 5.1 +/- 8 ng/g and that taken from sham rats was 22.8 +/- 1 ng/g (p < 0.001). These data demonstrate that the liver is essential for the normal postprandial excretion of sodium following ingestion of a high salt meal in rats.

Animals↗
PubMed1994

Spontaneous changes in arterial blood pressure and renal interstitial hydrostatic pressure in conscious rats.

1. Previous work has demonstrated a positive relationship between experimentally induced changes in arterial pressure (AP) and renal interstitial hydrostatic pressure (RIHP). The purpose of the present study was to test the hypothesis that RIHP is positively correlated with the normal changes in AP that occur spontaneously in conscious rats. 2. Rats were chronically instrumented for the recording of AP (via an aortic catheter) and RIHP. RIHP was measured by implanting a Millar microtransducer, whose tip had been encapsulated in a 35 microns pore polyethylene matrix (5 mm long, 2 mm o.d.), approximately 5 mm below the renal cortical surface. 3. A total of 56 h of simultaneous analog recording of AP and RIHP was obtained from ten rats. Each 1 h segment was digitized and evaluated at frequencies of 1, 0.1, 0.02 and 0.01 Hz. 4. In forty-nine out of fifty-six of these 1 h recordings taken at 1 Hz, there were significant positive linear correlations between AP and RIHP (mean r = 0.32) with a mean slope of 0.11 mmHg RIHP/1 mmHg AP. Low-pass filtering to 0.01 Hz significantly increased the r value to 0.48. 5. These results demonstrate that spontaneous changes in AP and RIHP are positively correlated. The spontaneous coupling of AP and RIHP may be of importance in the regulation of salt and water excretion by the pressure diuresis mechanism.

Anesthesia↗
PubMed1993

Evaluation of spontaneous baroreflex sensitivity in conscious dogs.

1. We evaluated a method of measuring cardiac baroreflex sensitivity (BRS) derived from spontaneous changes in systolic pressure (SP). SP was measured from the ECG signal in seven conscious, resting dogs. 2. Beat-to-beat changes in PI (dPI) were positively correlated with beat-to-beat changes in SP (dSP) in all dogs tested, suggesting spontaneous baroreflex function. The slope of the regression of dPI on dSP was used as an index of spontaneous BRS. 3. The spontaneous BRS was abolished by hexamethonium, atropine and bilateral carotid sinus denervation. Low dose atropine sulphate produced a paradoxical increase in spontaneous BRS, which has been observed in other studies. The spontaneous BRS was positively correlated with the average pulse interval in resting dogs. 4. Random modulation of heart rate after vagotomy failed to reproduce the strong positive correlation between dSP and dPI; this demonstrated that the correlation was not the result of mechanical coupling between heart rate and arterial blood pressure. 5. The BRS was measured pharmacologically in six dogs using a bolus injection of a vasoconstrictor. The pharmacological BRS was positively correlated with the spontaneous BRS measured after the bolus injection. 6. Finally, the spontaneous BRS was negatively correlated with the average arterial pressure in resting dogs. We conclude that the spontaneous BRS is a useful quantitative indicator of baroreflex function in conscious resting dogs.

Animals↗