Ventilatory Responses of Aged Male and Female Rats to Hypercapnia and to Hypoxia

Schlenker, Evelyn H.; Goldman, Max

doi:10.1159/000212713

Cited by 22 publications

(15 citation statements)

References 15 publications

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“…In this respect, it should be recognized that the Dia m is not a load-bearing muscle, and it is further distinguished by a unique activation history compared with limb muscles. The duty cycle (proportion of time active vs. inactive) of the Dia m is very high compared with that of limb muscles (ϳ40% compared with ϳ2% for the extensor digitorum longus muscle and ϳ14% for the soleus muscle) (25,42). Therefore, the effects of Hyp in limb muscles cannot be directly extrapolated to the Dia m .…”

Section: Discussionmentioning

confidence: 99%

Effects of hypothyroidism on maximum specific force in rat diaphragm muscle fibers

Geiger

Cody²,

Han³

et al. 2002

Journal of Applied Physiology

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Effects of hypothyroidism on maximum specific force in rat diaphragm muscle fibers. J Appl Physiol 92: 1506-1514, 2002.. First published January 7, 2002 10.1152/japplphysiol.00095.2001.-We hypothesized that 1) hypothyroidism (Hyp) decreases myosin heavy chain (MHC) content per half-sarcomere in diaphragm muscle (Diam) fibers, 2) Hyp decreases the maximum specific force (Fmax) of Diam fibers because of the reduction in MHC content per half-sarcomere, and 3) Hyp affects MHC content per half-sarcomere and Fmax to a greater extent in fibers expressing MHC type 2X (MHC2X) and/or MHC type 2B (MHC2B). Studies were performed on single Triton X-permeabilized fibers activated at pCa 4.0. MHC content per half-sarcomere was determined by densitometric analysis of SDS-polyacrylamide gels and comparison with a standard curve of known MHC concentrations. After 3 wk of Hyp, MHC content per half-sarcomere was reduced in fibers expressing MHC2X and/or MHC2B. On the basis of electron-microscopic analysis, this reduction in MHC content was also reflected by a decrease in myofibrillar volume density and thick filament density. Hyp decreased Fmax across all MHC isoforms; however, the greatest decrease occurred in fibers expressing fast MHC isoforms (ϳ40 vs. ϳ20% for fibers expressing slow MHC isoforms). When normalized for MHC content per half-sarcomere, force generated by Hyp fibers expressing MHC2A was reduced compared with control fibers, whereas force per half-sarcomere MHC content was higher for fibers expressing MHC2X and/or MHC2B in the Hyp Diam than for controls. These results indicate that the effect of Hyp is more pronounced on fibers expressing MHC 2X and/or MHC2B and that the reduction of Fmax with Hyp may be at least partially attributed to a decrease in MHC content per half-sarcomere but not to changes in force per cross bridge. thyroid hormone levels; skinned fibers; myosin heavy chain content; force per cross bridge MYOSIN HEAVY CHAIN (MHC) isoform expression forms the basis of fiber type classification in skeletal muscle, and contractile characteristics of skeletal muscle are correlated with MHC isoform expression (3,37,40,43,44). Thyroid hormone has been shown to modulate MHC gene expression and isoform composition in adult skeletal muscle fibers (10,13,22,29,30,32,34,51). However, the effects of thyroid hormone in the rat diaphragm muscle (Dia m ) are controversial. For example, previous studies have shown that hypothyroidism (Hyp) has no effect on the rat Dia m (29), whereas others have shown an increase in the relative number of type I Dia m fibers and a decrease in Dia m oxidative enzyme capacity (28). Previous results from our laboratory demonstrated changes in relative MHC isoform composition, a decrease in maximum specific force (F max ), and a slowing of maximum shortening velocity in adult Dia m bundles after 3 wk of Hyp (22).Studies from our laboratory and others indicate that the F max of single fibers differs with MHC isoform expression (3,18,19,43,44). Dia m fibers expressing MHC type 2X (MHC 2X ) alone...

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Section: Discussionmentioning

confidence: 99%

Effects of hypothyroidism on maximum specific force in rat diaphragm muscle fibers

Geiger

Cody²,

Han³

et al. 2002

Journal of Applied Physiology

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“…respiratory control; plasticity; age; sex hormones AGE AFFECTS THE CONTROL OF breathing in humans and other mammals (6,12,61,63), and there are striking differences between males and females with advancing age. For example, responses to hypoxia are decreased in middle-aged male rats but increased in middle-aged female rats (19,62,71,72). A form of serotonin (5-HT)-dependent respiratory plasticity, long-term facilitation (LTF), increases in middleaged female rats but decreases dramatically in middle-aged male rats (71, 72).…”

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confidence: 99%

Selected Contribution: Chronic intermittent hypoxia enhances respiratory long-term facilitation in geriatric female rats

Zabka¹,

Mitchell²,

Olson³

et al. 2003

Journal of Applied Physiology

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Zabka, A. G., G. S. Mitchell, E. B. Olson, Jr., and M. Behan. Selected Contribution: Chronic intermittent hypoxia enhances respiratory long-term facilitation in geriatric female rats. J Appl Physiol 95: 2614-2623. First published August 22, 2003 10.1152/japplphysiol.00476.2003.-Age and the estrus cycle affect time-dependent respiratory responses to episodic hypoxia in female rats. Respiratory long-term facilitation (LTF) is enhanced in middle-aged vs. young female rats (72). We tested the hypothesis that phrenic and hypoglossal (XII) LTF are diminished in acyclic geriatric rats when fluctuating sex hormone levels no longer establish conditions that enhance LTF. Chronic intermittent hypoxia (CIH) enhances LTF (41); thus we further predicted that CIH would restore LTF in geriatric female rats. LTF was measured in young (3-4 mo) and geriatric (20-22 mo) female Sasco Sprague-Dawley rats and in a group of geriatric rats exposed to 1 wk of nocturnal CIH (11 vs. 21% O 2 at 5-min intervals, 12 h/night). In anesthetized, paralyzed, vagotomized, and ventilated rats, time-dependent hypoxic phrenic and XII responses were assessed. The short-term hypoxic response was measured during the first of three 5-min episodes of isocapnic hypoxia (arterial PO 2 35-45 Torr). LTF was assessed 15, 30, and 60 min postepisodic hypoxia. Phrenic and XII short-term hypoxic response was not different among groups, regardless of CIH treatment (P Ͼ 0.05). LTF in geriatric female rats was smaller than previously reported for middle-aged rats but comparable to that in young female rats. CIH augmented phrenic and XII LTF to levels similar to those of middle-aged female rats without CIH (P Ͻ 0.05). The magnitude of phrenic and XII LTF in all groups was inversely related to the ratio of progesterone to estradiol serum levels (P Ͻ 0.05). Thus CIH and sex hormones influence the magnitude of LTF in geriatric female rats. respiratory control; plasticity; age; sex hormones AGE AFFECTS THE CONTROL OF breathing in humans and other mammals (6,12,61,63), and there are striking differences between males and females with advancing age. For example, responses to hypoxia are decreased in middle-aged male rats but increased in middle-aged female rats (19,62,71,72). A form of serotonin (5-HT)-dependent respiratory plasticity, long-term facilitation (LTF), increases in middleaged female rats but decreases dramatically in middle-aged male rats (71, 72). The control of breathing is also influenced by sex hormones (7, 60, 66). However, relatively little is known concerning specific mechanisms of respiratory control affected by age and/or sex hormones.In the present study, we investigated the effects of old age on selected time-dependent respiratory responses during and after episodic hypoxia in female rats, with a focus on the short-term hypoxic response (STHR) and LTF. STHR and LTF have been studied extensively in young and middle-aged, but not in geriatric, male and female rats (20,50,58,71,72).Respiratory LTF is a form of plasticity elicited by episodic hypoxia or e...

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“…To evaluate ventilation, the barometric technique routinely employed in our laboratory [2]was used. During ventilatory measurements, the chamber was sealed except for a fixed small leak that stabilized recordings.…”

Section: Methodsmentioning

confidence: 99%

“…Frequency of breathing and V T were measured from an average of 10 breaths per condition (air, hypoxia or hypercapnia). Oxygen consumption was determined using the flow-through method that consists of measuring the difference between the fractional contents of oxygen entering and exiting the chamber multiplied by the flow rate through the chamber and corrected for the respiratory quotient and STPD conditions [2]. …”

Section: Methodsmentioning

confidence: 99%

“…Gender differences in control of breathing have been reported in rats and human beings, especially in response to gas challenges such as hypoxia and hypercapnia [1, 2, 3]. These challenges are used experimentally to ascertain the capability of central and peripheral chemosensors to sense and of individuals to respond to alterations in oxygen and carbon dioxide levels in the blood and to determine if animals can maintain homeostasis [4].…”

Section: Introductionmentioning

confidence: 99%

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Gender Comparisons of Control of Breathing and Metabolism in Conscious Mice Exposed to Cold

Schlenker

Hansen²,

Pfaff³

2002

Neuroendocrinology

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We evaluated the effects of 2 h of warm (24°C) and cold (6°C) exposure on metabolism and ventilation (v̇_E) in conscious male and female Harlan ICR Swiss Webster mice exposed to air, and 8% O₂ in N₂ (hypoxia) and to 5% CO₂ in O₂ (hypercapnia) for 2 min each at both temperatures. All cold-exposed mice increased O₂ consumption (v̇_O2), and maintained body temperature. Cold-exposed females doubled their tidal volume, increased their v̇_E fivefold, and doubled their ventilatory equivalent to v̇_O2 (v̇_E/v̇_O2). In contrast, cold-exposed males decreased tidal volume and doubled v̇_E relative to warm exposure. The ventilatory equivalent of males was similar during warm and cold exposure. During warm exposure, mice of both genders increased their ventilatory responses to both hypoxia and to hypercapnia by different mechanisms. In contrast, during cold exposure, these responses were blunted relative to air measurements in females and decreased below air values in males. Thus, cold exposure was able to elicit gender-specific ventilatory and metabolic responses.

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Ventilatory Responses of Aged Male and Female Rats to Hypercapnia and to Hypoxia

Cited by 22 publications

References 15 publications

Effects of hypothyroidism on maximum specific force in rat diaphragm muscle fibers

Effects of hypothyroidism on maximum specific force in rat diaphragm muscle fibers

Selected Contribution: Chronic intermittent hypoxia enhances respiratory long-term facilitation in geriatric female rats

Gender Comparisons of Control of Breathing and Metabolism in Conscious Mice Exposed to Cold

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