Age-related changes in colonic function in rats

1984 ◽  
Vol 247 (5) ◽  
pp. G542-G546 ◽  
Author(s):  
J. N. McDougal ◽  
M. S. Miller ◽  
T. F. Burks ◽  
D. L. Kreulen

Aging in humans is associated with changes in gastrointestinal function. We wanted to determine whether a similar phenomenon occurs in rats and whether rats would be a suitable model to study changes in the gastrointestinal tract with age. Intestinal transit, response in vitro of circular colon strips to bethanechol and electrical stimulation, and colonic smooth muscle histology were compared for post-pubertal (5-12 mo) and senescent (25-28 mo) male Fischer 344 rats. Colonic transit of 51Cr was decreased 45% in senescent rats in comparison with younger rats. The maximum response of circularly oriented muscle strips from senescent rats to electrical stimulation of nerves was 32% less than the maximum response of strips from postpubertal rats. Likewise, the maximum response of the muscle strips to bethanechol was 16% less in the senescent group compared with the postpubertal group. There was no difference between the two groups in the EC50 of bethanechol. The thickness of the muscle layers and the percent circular muscle of strips fixed at optimum length were the same in both age groups. The senescent rat appears to be a useful model for the study of gastrointestinal changes with aging.

1990 ◽  
Vol 258 (3) ◽  
pp. G447-G453 ◽  
Author(s):  
E. V. O'Loughlin ◽  
D. M. Hunt ◽  
D. Kreutzmann

Postnatal changes in adrenal gluco- and mineralocorticoid secretion and colonic sodium and chloride transport were examined. New Zealand White rabbits, age 10-14, 18-22, and 25-30 days, and adult animals (6-10 wk) were studied. Serum cortisol, corticosterone, aldosterone, and mucosal Na(+)-K(+)-ATPase activities were measured in each age group. Transport studies were performed in vitro under short-circuited conditions in distal colon at all age groups and in proximal colon in days 10-14 and 18-22 and in adult animals. Serum glucocorticoids varied little until after day 30 when they rose to adult levels. On the other hand, serum aldosterone levels were two- to threefold higher in days 10-14 and 18-22 animals but fell to adult levels by day 25. In distal colon, amiloride-inhibitable electrogenic Na+ absorption was present at all ages but was significantly greater (P less than 0.01) in days 10-14 (3.8 +/- 0.5 mu eq.cm-2.h-1) and 18-22 (4.2 +/- 0.4) rabbits compared with adults (1.9 +/- 0.4) but not day 25-30 (2.8 +/- 0.5). In proximal colon, Na+ absorption was significantly higher (P less than 0.05) in day 10-14 (1.6 +/- 0.5 mu eq.cm-2.h-1) compared with day 18-22 (-0.2 +/- 0.5) and adults (0.06 +/- 0.5) and was amiloride insensitive. Neither chloride transport nor mucosal Na(+)-K(+)-ATPase demonstrated significant age-related changes in either region of colon. These results indicate that both proximal and distal colonic Na+ transport undergoes postnatal changes. In distal but not proximal colon these changes appear to be regulated by circulating aldosterone probably by increasing apical membrane permeability to Na+.


1977 ◽  
Vol 232 (6) ◽  
pp. E580
Author(s):  
M P Zabinski ◽  
P Biancani

Longitudinal force-length relationship of the rat esophagus was studied in vitro in three age groups: 1 mo, 3 mo, and 12 mo. The length of maximum force development (MFD) occurs at 1.4-1.5 times the in vivo length for all age groups. The active force developed at MFD increases markedly with age. The difference in the active forces in the 3-mo and 12-mo age groups is due to differences in cross section because the active stress of the esophagus in the longitudinal direction is approximately equal for the two age groups. The active stress in the 1-mo-old rats is lower than in the 3-mo-old rats, suggesting an increased contractility of the esophagus with age in this period of development.


1996 ◽  
Vol 80 (2) ◽  
pp. 445-451 ◽  
Author(s):  
S. K. Powers ◽  
D. Criswell ◽  
R. A. Herb ◽  
H. Demirel ◽  
S. Dodd

Recent evidence demonstrates that aging results in an increase in fast (type IIB) myosin heavy chain (MHC) in the rat diaphragm. It is unknown whether this age-related change in fast MHC influences the diaphragmatic maximal shortening velocity (Vmax). Therefore, we tested the hypothesis that aging is associated with an increase in the diaphragmatic Vmax and that the increase in the Vmax is highly correlated with the percentage of type IIb MHC. In vitro contractile properties were measured with costal diaphragm strips obtained from young (4 mo old; n = 8) and (old 24 mo old; n = 8) male Fischer-344 rats. Diaphragmatic maximal tetanic specific force production was 14.5% lower in the old compared with the young animals (23.0 +/- 0.4 vs. 19.7 +/- 0.8 N/cm2; P < 0.05). In contrast, the diaphragmatic Vmax was significantly higher in the old compared with the young animals (5.5 +/- 0.1 vs. 4.4 +/- 0.3 lengths/s; P < 0.05). Although the percent type IIb MHC was significantly higher (approximately +14%; P < 0.05) in the old compared with the young animals, the correlation between Vmax and percent type IIb MHC was relatively low (r = 0.50; P = 0.05). These data support the hypothesis that an age-related increase in diaphragmatic Vmax occurs; however, factors in addition to type IIb MHC are involved in regulating diaphragmatic Vmax. Interestingly, although aging resulted in a decrease in diaphragmatic maximal specific force production, power output at all muscle loads was maintained in the old animals due to the increase in diaphragmatic shortening velocity.


2000 ◽  
Vol 279 (6) ◽  
pp. H2807-H2814 ◽  
Author(s):  
William E. Schutzer ◽  
Hong Xue ◽  
John F. Reed ◽  
Jean-Baptiste Roullet ◽  
Sharon Anderson ◽  
...  

β-Adrenergic receptor (β-AR)-mediated (cAMP-dependent) vasorelaxation declines with advancing age. It has been shown that angiotensin II (ANG II), a potent vasoconstrictor, enhances cAMP-mediated vasorelaxation. Therefore, we questioned whether ANG II could reverse age-related, impaired β-AR-mediated vasorelaxation and cAMP production. Pretreatment of aortic rings from 6-wk-old or 6-mo-old male Fischer 344 rats with ANG II significantly enhanced vasorelaxation induced by isoproterenol (Iso), a β-AR agonist, and forskolin, a direct activator of adenylyl cyclase, but not dibutyryl-cAMP or isobutylmethylxanthine. The ANG II effect was blocked by losartan but not PD-123319 and was not observed in the aortas from 12- and 24-mo-old animals. Iso-stimulated cAMP production in the aorta was enhanced in the presence of ANG II in the 6-wk-old and 6-mo-old age groups only. Results suggest ANG II cannot reverse the age-related impairment in β-AR-dependent vasorelaxation. We conclude aging may affect a factor common to both ANG II-receptors and β-AR signaling pathways or aging may impair cross-talk between these two receptor pathways.


1995 ◽  
Vol 74 (2) ◽  
pp. 876-887 ◽  
Author(s):  
D. Murchison ◽  
W. H. Griffith

1. Whole cell patch-clamp recordings were made of low-voltage-activated (LVA) calcium (Ca2+) currents using 2 mM barium (Ba2+) as charge carrier. Acutely dissociated neurons from medial septum (MS) and the nucleus of the diagonal band (nDB) were examined in young adult (1–3 mo) and aged (24–26 mo) Fischer 344 rats. 2. Most neurons in both age groups displayed LVA currents: 84% of young cells (110/131) and 87% in aged cells (62/71). Using cell capacitance as an indication of cell size, aged cells were significantly smaller (P < 0.05; 15.4 +/- 0.6 pF; mean +/- SE) than young cells (18.0 +/- 0.5 pF), although a single distribution of cell sizes was present in both populations. 3. The LVA currents were enhanced in cells from aged animals. When LVA currents were studied without activation of high voltage activated currents, the current density (pA/pF) was significantly (P < 0.05) increased at negative potentials in aged neurons (young: 4.92 +/- 0.35 pA/pF; Aged: 5.92 +/- 0.45 pA/pF, at a prepulse potential of -110 mV). No change in voltage-dependent activation or inactivation was seen. The time course of recovery from inactivation also was unchanged. 4. Kinetic parameters of LVA currents were compared in both age groups. No age-related difference in time-dependent activation or inactivation was observed. A single distribution of decay time constants of LVA currents was present in both age groups. 5. These results show that MS/nDB cells maintain robust LVA currents and have increased current densities in very old rats. An increased LVA current in the aged neurons suggests that their ability to fire rhythmically or in bursts is retained or enhanced and that the resulting increase in intracellular Ca2+ may contribute to an altered Ca2+ homeostasis.


1987 ◽  
Vol 65 (5) ◽  
pp. 773-777 ◽  
Author(s):  
D. J. Crankshaw

To test the hypothesis that binding site regulation is the primary process controlling the responsiveness of the rat's myometrium to oxytocin during pregnancy, I have studied the effects of oxytocin on longitudinal and circular strips of myometrium in vitro throughout pregnancy. Longitudinal muscle was as sensitive on day 10 of pregnancy (EC50 = 1.6 nM) as it was at term (EC50 = 1.3 nM) and there was no significant change in the mean maximal force developed in response to the hormone (2.1 ± 0.9 vs. 1.5 ± 0.3 N cm−2). Circular muscle on the other hand was essentially refractory to the hormone until day 21 of pregnancy at which time its sensitivity and the maximum response were similar to those of longitudinal muscle. These results indicated that regulation of oxytocin sensitivity in the two muscle layers was temporally different, and they suggested different mechanisms. The effect of oxytocin on longitudinal muscle was not compatible with the hypothesis that changes in binding site number regulate the responsiveness of the tissue, whereas the effect on circular muscle was.


1982 ◽  
Vol 93 (2) ◽  
pp. 177-181 ◽  
Author(s):  
Joseph Segal ◽  
B. R. Troen ◽  
S. H. Ingbar

Studies of the influence of age and sex on the concentrations of total thyroxine (T4) and 3,5,3′-tri-iodothyronine (T3) in serum and on the free T4 and free T3 indices, were conducted in Sprague–Dawley rats of the CD strain varying in age between 10 days and 12 months. Both sex- and age-related differences were found. In all age-groups studied, serum T4 concentrations were higher in the male than in the female, whereas serum T3 concentrations were higher in the female. In both sexes, concentrations of T4 and T3 in serum reached a peak early in life, between the first and second month of age, and declined thereafter. In addition, in both sexes the intensity of thyroid hormone binding, as judged from values of the in-vitro uptake of T3, did not change with age, suggesting that free T4 and T3 concentrations in the serum display the same sex differences and age-related changes as do the concentrations of total T4 and T3. It remains to be determined whether these sex-and age-related alterations in serum thyroid hormone concentration are expressed in differences in the activity of various thyroid hormone-dependent processes.


1990 ◽  
Vol 258 (1) ◽  
pp. R263-R268 ◽  
Author(s):  
L. K. Kullama ◽  
V. Balaraman ◽  
J. R. Claybaugh ◽  
W. M. Ichimura ◽  
K. T. Nakamura

This in vitro study examined the ontogeny of arginine vasopressin (AVP) and arginine vasotocin (AVT) compared with norepinephrine (NE)-mediated contraction in rat thoracic aortas. Aortas from three age groups (2-3 days, 6-7 days, and 12 wk) of Sprague-Dawley rats were used. Ring segment resting length was adjusted to optimize tension developed to a dose that produces half-maximal tension of NE in Krebs solution (pH 7.4, 37 degrees C) and gassed with 95% O2-5% CO2. Cumulative dose-response curves were generated for KCl (5-100 mM), NE (10(-10)-10(-5) M), AVP, and AVT (both 10(-10)-10(-6) M) in the presence and absence of a selective V1 vasopressinergic inhibitor, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine]arginine vasopressin ([d(CH2)5Tyr(Me)]AVP). A progressive increase in sensitivity among all age groups was found for KCl and NE. There was a slight decrease in sensitivity to both AVP and AVT in the 1st wk. Maximum contractile response to NE increased between 2-3 and 6-7 days, whereas no change was observed for KCl, AVP, or AVT. AVP- and AVT-mediated contractions were selectively inhibited by [d(CH2)5Tyr(Me)]-AVP. These results suggest 1) receptor-mediated contractility is present from 2 days of age for NE, AVP, and AVT; 2) sensitivity to KCl and NE increases progressively during postnatal development, whereas sensitivity to AVP and AVT slightly decreases in the 1st wk with no progressive age-related increase by 12 wk; 3) AVP and AVT mediate contraction via a similar V1-like receptor.


Endocrinology ◽  
2005 ◽  
Vol 146 (7) ◽  
pp. 3105-3112 ◽  
Author(s):  
John W. Kasckow ◽  
Tracy M. Segar ◽  
Chun Xiao ◽  
Amy R. Furay ◽  
Nathan K. Evanson ◽  
...  

Abstract Aging in rodents and primates is accompanied by changes in hypothalamic-pituitary-adrenal (HPA) activity. We examined behavioral and neuroendocrine responses in 3, 15-, and 30-month-old F344/Brown-Norway rats. Basal corticosterone and ACTH levels did not differ with age, although ACTH responses, but not corticosterone responses to restraint stress, were significantly lower in the 30-month-old group relative to 3- and 15-month-old rats. Induction of c-fos mRNA in the paraventricular nucleus from restraint was not affected by age. Furthermore, there was an enhanced sensitivity to dexamethasone suppression in aged animals as evidenced by lesser ACTH and corticosterone release after dexamethasone administration. Evaluation of emotional behaviors in the forced swim test revealed no differences between the age groups. With fear conditioning, aged rats had decreased freeze times relative to middle-aged or young rats. Regression analysis revealed no significant correlations between the behavioral and HPA axis data in any group. Overall, the data suggest that an apparent decrease in pituitary drive is compensated for at the level of the adrenal, resulting in stable patterns of glucocorticoid secretion. The lack of a correlation between HPA axis measures and emotional as well as fear conditioning-related behaviors indicates that corticosteroid dysfunction may not predict age-related behavioral deficits in this aging model.


Author(s):  
Nataļja Kurjāne ◽  
Rūta Brūvere ◽  
Natālija Gabruševa ◽  
Elvīra Hagina ◽  
Tija Zvagule ◽  
...  

Ageing and production of the cytokines in Chernobyl clean-up workers from Latvia Chronic low-grade inflammation with subsequent impairment of immune system function promotes the development of age-related diseases, such as cancers, degenerative and infection diseases. It is not yet clear, if exposure to ionising radiation accelerates the aging process. The aim of the present work was to estimate the production of several cytokines by peripheral blood cells of Latvia's Chernobyl clean-up workers depending on age. ELISA was employed to determine the plasma level of sIL-1β and sIL-6 as well as level of IL-4 and TNF-α spontaneous and 24h and 96h after in vitro stimulation of peripheral blood mononuclear cell cultures by lipopolysaccharide (LPS) and phytohemagglutinin (PHA) mitogens were determined in 40 Chernobyl clean-up workers 17 years after their work in Chernobyl and in 42 blood-donors without a history of occupational radiation exposure. The ability of peripheral blood leukocytes (PBL) to produce interferons (IFNs) was determined in 73 Chernobyl clean-up workers 15 years after the work in Chernobyl and in age-matched 63 blood-donors. IFNs were tested in whole blood cultures by standard virus cytopathic inhibition micromethod after their in vitro induction by Newcastle disease virus, phytohemagglutinin or double-stranded RNA. Individuals were divided into three age groups: age < 40, age 40-49 and age > 50. The ability of PBL to produce IFN was significantly decreased in all Chernobyl clean-up worker age groups in comparison with blood-donors (control groups). The incidence of good ability to produce IFN gradually decreased with age in the control group, but increased with age in aged-matched Chernobyl clean-up workers groups. The production TNF-α and IL-4 by peripheral blood mononuclear cells as well as sIL-1β level in plasma showed no significant differences between all the examined age groups. The sIL-6 level was gradually increased with age in Chernobyl clean-up workers. Our results showed that the concentration of pro-inflammation cytokine sIL-6 in peripheral blood plasma, as well as the ability of PBL to produce IFNs, in Chernobyl clean-up workers from Latvia is age dependent.


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