scholarly journals Aging and arteriosclerosis. I. Development of myointimal hyperplasia after endothelial injury.

1986 ◽  
Vol 164 (4) ◽  
pp. 1171-1178 ◽  
Author(s):  
R J Hariri ◽  
D R Alonso ◽  
D P Hajjar ◽  
D Coletti ◽  
M E Weksler
Keyword(s):  
Vascular Injury ◽  
Experimental Models ◽  
Endothelial Injury ◽  
Vascular Lesions ◽  
Fischer 344 Rats ◽  
Cell Nuclei ◽  
Fischer 344 ◽  
Endothelial Denudation ◽  
Old Rats ◽  
Intimal Thickness

Old Fischer 344 rats are more susceptible to vascular lesions after arterial endothelial injury than are young animals. Thus, 20-26-mo-old Fischer 344 rats developed greater and more persistent intimal proliferative lesions than did 2-5-mo-old rats after aortic endothelial denudation. 3 d after deendothelialization, intimal thickness was increased two-fold in both old and young animals. However, 14 d after endothelial injury, intimal thickness had increased nearly five times in old animals, but had regressed to normal in young animals. Intimal thickness of young aortic grafts transplanted into young recipients did not differ significantly from adjacent host aorta or autotransplanted aortic segments 6 wk after surgery. In contrast, intimal thickness of old grafts transplanted into young recipients was eight times greater than adjacent young host aorta 6 wk after surgery. The density of cell nuclei in the intima of old grafts was also much greater than that in young grafts. Thus, in two experimental models of vascular injury, old rats have consistently had greater myointimal hyperplasia than young rats. The increased proliferative response of aortic smooth muscle cells after vascular injury of old animals may contribute to the increased prevalence of vascular disease with age.

Overexpression of PKC-βI and -δ contributes to higher PKC activity in the proximal tubules of old Fischer 344 rats

2003 ◽  
Vol 285 (6) ◽  
pp. F1100-F1107 ◽  
Author(s):  
Mohammad Asghar ◽  
Tahir Hussain ◽  
Mustafa F. Lokhandwala
Keyword(s):  
Skf 38393 ◽  
Proximal Tubules ◽  
Fischer 344 Rats ◽  
Adult Rats ◽  
Altered Expression ◽  
Fischer 344 ◽  
Pkc Isoforms ◽  
Diuretic Response ◽  
Old Rats ◽  
Pkc Ζ

Previously, we reported that natriuretic and diuretic response to dopamine is diminished in old Fischer 344 rats, which is due to higher basal protein kinase C (PKC) activity and hyperphosphorylation of Na-K-ATPase in the proximal tubules (PTs) of old rats. The present study was conducted to determine whether higher PKC activity could be due to altered expression of some of the PKC isoforms in the superficial cortex (rich in PTs) of old rats. Fluorimetric measurement showed almost twofold increase in the PKC activities in homogenates and membranes of old (24 mo) compared with adult (6 mo) rats. Interestingly, in the basal state PKC-βI was overexpressed in the membranes, whereas PKC-δ expression was increased in the cytosol of old compared with adult rats. Treatment of the cortical slices with either SKF-38393, a D1-like agonist, or PDBu, a direct activator of PKC, caused translocation of PKC-βI from cytosol to membranes in adult but not in old rats. Both of these drugs caused translocation of PKC-δ from membranes to cytosol in adult but not in old rats. These drugs had no effect on translocation of PKC-ζ in both adult and old rats. Both PKC-βI and -δ coimmunoprecipiated with α1-subunit of Na-K-ATPase in adult and old rats. These observations suggest that both SKF-38393 and PDBu differentially regulate PKC-βI and -δ in adult but not in old rats. Also, PKC-βI and -δ seem to interact with Na-K-ATPase in these animals. The overexpression of both PKC-βI and -δ in old rats could be responsible for a higher basal PKC activity, which causes the hyperphosphorylation of Na-K-ATPase and contributes to the diminished inhibition of Na-K-ATPase activity by dopamine in old rats.

NAD(P)H oxidase-generated superoxide anion accounts for reduced control of myocardial O2 consumption by NO in old Fischer 344 rats

2003 ◽  
Vol 285 (3) ◽  
pp. H1015-H1022 ◽  
Author(s):  
Alexandra Adler ◽  
Eric Messina ◽  
Ben Sherman ◽  
Zipping Wang ◽  
Harer Huang ◽  
...  
Keyword(s):  
Oxidant Stress ◽  
Heart Weight ◽  
Fischer 344 Rats ◽  
No Donor ◽  
Fischer 344 ◽  
Old Rats ◽  
Fischer Rats ◽  
Enos Protein

We investigated the role of nitric oxide (NO) in the control of myocardial O2 consumption in Fischer 344 rats. In Fischer rats at 4, 14, and 23 mo of age, we examined cardiac function using echocardiography, the regulation of cardiac O2 consumption in vitro, endothelial NO synthase (eNOS) protein levels, and potential mechanisms that regulate superoxide. Aging was associated with a reduced ejection fraction [from 75 ± 2%at4moto66 ± 3% ( P < 0.05) at 23 mo] and an increased cardiac diastolic volume [from 0.60 ± 0.04 to 1.00 ± 0.10 ml ( P < 0.01)] and heart weight (from 0.70 ± 0.02 to 0.90 ± 0.02 g). The NO-mediated control of cardiac O2 consumption by bradykinin or enalaprilat was not different between 4 mo (36 ± 2 or 34 ± 3%) and 14 mo (29 ± 1 or 25 ± 3%) but markedly ( P < 0.05) reduced in 23-mo-old Fischer rats (15 ± 3 or 7 ± 2%). The response to the NO donor S-nitroso- N-acetyl penicillamine was not different across groups (35%, 35%, and 44%). Interestingly, the eNOS protein level was not different at 4, 14, and 23 mo. The addition of tempol (1 mmol/l) to the tissue bath eliminated the depression in the control of cardiac O2 consumption by bradykinin (25 ± 3%) or enalaprilat (28 ± 3%) in 23-mo-old Fischer rats. We next examined the levels of enzymes involved in the production and breakdown of superoxide. The expression of Mn SOD, Cu/Zn SOD, extracellular SOD, and p67phox, however, did not differ between 4- and 23-mo-old rats. Importantly, there was a marked increase in gp91phox, and apocynin restored the defect in NO-dependent control of cardiac O2 consumption at 23 mo to that seen in 4-mo-old rats, identifying the role of NADPH oxidase. Thus increased biological activity of superoxide and not decreases in the enzyme that produces NO are responsible for the altered control of cardiac O2 consumption by NO in 23-mo-old Fischer rats. Increased oxidant stress in aging, by decreasing NO bioavailability, may contribute not only to changes in myocardial function but also to altered regulation of vascular tone and the progression of cardiac or vascular disease.

Age-related immunosenescence in Fischer 344 rats: influence of exercise training

1992 ◽  
Vol 73 (5) ◽  
pp. 1932-1938 ◽  
Author(s):  
I. Nasrullah ◽  
R. S. Mazzeo
Keyword(s):  
Endurance Training ◽  
Interleukin 2 ◽  
Cytolytic Activity ◽  
Treadmill Running ◽  
Target Cells ◽  
Fischer 344 Rats ◽  
Middle Aged ◽  
Fischer 344 ◽  
Age Related ◽  
Old Rats

The present investigation examined the extent to which 15 wk of endurance training could influence immune function in young, middle-aged, and older animals. Forty-eight male Fischer 344 rats were divided into trained and untrained groups. Training consisted of treadmill running at 75% maximal running capacity for 1 h/day, 5 days/wk, for 15 wk. Animals were killed at 8, 17, and 27 mo, at which time splenocytes were isolated. The capacity for lymphocyte proliferation in response to mitogen (concanavalin A, ConA), interleukin-2 (IL-2) production, and cytolytic activity against YAC-1 target cells was determined. ConA-induced proliferation declined significantly with age. Training suppressed the proliferative response in the young (-41%) and middle-aged animals (-27%) compared with the age-matched controls; however, training improved this response (+58%) in the older group. IL-2 production followed a pattern similar to that for mitogen-induced proliferation, such that production declined with age and was reduced with training in young and middle-aged animals but was significantly more improved in the older animals than in age-matched controls. The ability to lyse target cells, measured as percent cytotoxicity, declined steadily with advancing age at all effector-to-target cell ratios tested: 52, 14, and -16% for 8-, 17-, and 27-mo-old rats, respectively. It was concluded that the capacity for ConA-induced splenocyte proliferation, IL-2 production, and cytolytic activity declines significantly with advancing age. Furthermore, 15 wk of endurance training suppressed proliferation and IL-2 production in young animals but improved these responses in older animals. Training had no effect on cytolytic activity.

Effect of age on induction of hepatic phosphoenolpyruvate carboxykinase by fasting

1994 ◽  
Vol 267 (2) ◽  
pp. G195-G200 ◽  
Author(s):  
H. Van Remmen ◽  
W. F. Ward
Keyword(s):  
G Protein ◽  
Time Course ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Age Groups ◽  
Fischer 344 Rats ◽  
Fischer 344 ◽  
Fasting And Refeeding ◽  
Old Rats ◽  
Rate Limiting ◽  
Effect Of Age

This study examines the effect of age on the induction of the rate-limiting enzyme in gluconeogenesis, phosphoenolpyruvate carboxykinase (PEPCK), in response to fasting and refeeding in male Fischer 344 rats aged 3-18 mo. The rats were fasted for 30 h to increase the activity of PEPCK and subsequently were refed for 24 h to lower activity toward basal levels. PEPCK activity increased 2.2-fold in the 3-mo-old rats and 2.3-fold in the 18-mo-old rats during the 30-h fast. Therefore PEPCK induction during the 30-h fast was not altered with age. Similarly, refeeding resulted in a significant decrease in PEPCK activity at all ages. After the 24-h refeeding period, the rats were fasted a second time, and the time course of induction from the basal refed level was measured. In the young rats (6 mo), the activity of PEPCK increased rapidly from 18.12 +/- 1.61 to 42.66 +/- 5.94 U/g protein (P < 0.01) within 8 h of fasting. However, in the 18-mo-old rats, the initiation of the induction of PEPCK activity was delayed, and, after 12 h, PEPCK activity had increased from 17.34 +/- 1.34 to only 32.50 +/- 3.21 U/g protein (P < 0.01). Furthermore, the rate of induction appears to be decreased in the older animals. The activity after 24 h of fasting was equivalent in all four age groups (ranging from 44.72 +/- 5.38 at 3 mo to 40.18 +/- 5.42 U/g protein at 18 mo).(ABSTRACT TRUNCATED AT 250 WORDS)

An age-related difference in hyperoxia lethality: role of lung antioxidant defense mechanisms

1995 ◽  
Vol 268 (4) ◽  
pp. L539-L545 ◽  
Author(s):  
A. T. Canada ◽  
L. A. Herman ◽  
S. L. Young
Keyword(s):  
Defense Mechanisms ◽  
Antioxidant Defense ◽  
Fischer 344 Rats ◽  
Fischer 344 ◽  
Related Difference ◽  
Age Related ◽  
65 H ◽  
Old Rats ◽  
Gpx Activity

The role of animal age in the lethal response to > 98% oxygen has been extensively studied, with the observation that neonatal rats were resistant while mature animals were sensitive. Antioxidant enzymes increased during the oxygen exposure in neonatal but not in mature rats, suggesting they were important in the age-related toxicity difference. Because no studies had compared the response of mature and old rats to hyperoxia, we exposed Fischer 344 rats, aged 2 and 27 mo, to > 98% oxygen. Unexpectedly, the old rats lived significantly longer than young, 114 and 65 h, respectively. No histopathological differences were found to explain the results. Of the antioxidants, only glutathione peroxidase (GPx) activity was higher in the lungs of nonexposed old rats. Superoxide dismutase (SOD) was higher in the young, results opposite those expected if SOD was important in the lethality difference. No antioxidant induction occurred in the old oxygen-exposed rats. These results suggest that although there may be a role for GPx, mechanisms in addition to antioxidant protection and inflammation are likely responsible for the age-related difference in hyperoxia lethality.

scholarly journals Muscle adaptations to hindlimb suspension in mature and old Fischer 344 rats

1997 ◽  
Vol 82 (6) ◽  
pp. 1875-1881 ◽  
Author(s):  
Craig S. Stump ◽  
Charles M. Tipton ◽  
Erik J. Henriksen
Keyword(s):  
Cardiac Muscle ◽  
Old Age ◽  
Glucose Transporter ◽  
Citrate Synthase ◽  
Hindlimb Suspension ◽  
Fischer 344 Rats ◽  
Fischer 344 ◽  
Glut 4 ◽  
Hindlimb Muscles ◽  
Old Rats

Stump, Craig S., Charles M. Tipton, and Erik J. Henriksen.Muscle adaptations to hindlimb suspension in mature and old Fischer 344 rats. J. Appl. Physiol.82(6): 1875–1881, 1997.—We examined skeletal and cardiac muscle responses of mature (8 mo) and old (23 mo) male Fischer 344 rats to 14 days of hindlimb suspension. Hexokinase (HK) and citrate synthase (CS) activities and GLUT-4 glucose transporter protein level, which are coregulated in many instances of altered neuromuscular activity, were analyzed in soleus (Sol), plantaris (Pl), tibialis anterior (TA), extensor digitorum longus (EDL), and left ventricle. Protein content was significantly ( P < 0.05) lower in all four hindlimb muscles after suspension compared with controls in both mature (21–44%) and old (17–43%) rats. Old rats exhibited significantly lower CS activities than mature rats for the Sol, Pl, and TA. HK activities were significantly lower in the old rats for the Pl (19%) and TA (33%), and GLUT-4 levels were lower in the old rats for the TA (38%) and EDL (24%) compared with the mature rats. Old age was also associated with a decrease in CS activity (12%) and an increase in HK activity (14%) in cardiac muscle. CS activities were lower in the Sol (20%) and EDL (18%) muscles from mature suspended rats and in the Sol (25%), Pl (27%), and EDL (25%) muscles from old suspended rats compared with corresponding controls. However, suspension was associated with significantly higher HK activities for all four hindlimb muscles examined, in both old (16–57%) and mature (10–43%) rats, and higher GLUT-4 concentrations in the TA muscles of the old rats (68%) but not the mature rats. These results indicate that old age is associated with decreased CS and HK activities and GLUT-4 protein concentration for several rat hindlimb muscles, and these variables are not coregulated during suspension. Finally, old rat skeletal muscle appears to respond to suspension to a similar or greater degree than mature rat muscle responds.

Sensitivity of lungs of aging Fischer 344 rats to ozone: assessment by bronchoalveolar lavage

1996 ◽  
Vol 271 (4) ◽  
pp. L555-L565 ◽  
Author(s):  
R. Vincent ◽  
D. Vu ◽  
G. Hatch ◽  
R. Poon ◽  
K. Dreher ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Biological Effects ◽  
Age Groups ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Ozone Exposure ◽  
Fischer 344 Rats ◽  
Adult Rats ◽  
Fischer 344 ◽  
Old Rats

Biological effects indicators in bronchoalveolar lavage fluid were studied in Fischer 344 rats of different ages after exposure to 0.4-0.8 ppm ozone for periods of 2-6 h on a single day or on 4 consecutive days. The magnitude of alveolar protein transudation induced by ozone was not different between age groups, but the interindividual variability of protein changes was higher in senescent (24-mo-old) rats. By comparison to juvenile (2-mo-old) and adult (9-mo-old) rats, senescent animals had higher increases of interleukin-6 (up to 10-fold higher) and N-acetyl-beta-D-glucosaminidase (NAGA; 2-fold higher) in lung lavage after ozone. Ascorbic acid was lower in lungs of senescent rats (one-half of juvenile values), and acute ozone exposure brought a further decrease in lung ascorbate. Whereas alveolar protein transudation was attenuated after ozone exposure on 4 days, persistent elevation of NAGA in senescent rats suggested only partial adaptation. Injection of endotoxin did not modify the patterns of effects. Incorporation of 18O-ozone into macrophages and surfactant was not different between age groups, indicating that the magnified biological responses in senescent rats were not dominated by differences in internal dose of ozone. The results indicate that senescent rats respond differently than juvenile and adult rats to lung injury.

Reduced feeding response to neuropeptide Y in senescent Fischer 344 rats

2001 ◽  
Vol 280 (4) ◽  
pp. R1052-R1060 ◽  
Author(s):  
Cynthia A. Blanton ◽  
Barbara A. Horwitz ◽  
James E. Blevins ◽  
Jock S. Hamilton ◽  
Eduardo J. Hernandez ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Neuropeptide Y ◽  
Body Weight Loss ◽  
Fischer 344 Rats ◽  
Feeding Response ◽  
Fischer 344 ◽  
Progressive Weight Loss ◽  
Old Rats

The anorexia of aging syndrome in humans is characterized by spontaneous body weight loss reflecting diminished food intake. We reported previously that old rats undergoing a similar phenomenon of progressive weight loss (i.e., senescent rats) also display altered feeding behavior, including reduced meal size and duration. Here, we tested the hypothesis that blunted responsiveness to neuropeptide Y (NPY), a feeding stimulant, occurs concurrently with senescence-associated anorexia/hypophagia. Young (8 mo old, n = 9) and old (24–30 mo old, n = 11) male Fischer 344 rats received intracerebroventricular NPY or artificial cerbrospinal fluid injections. In response to a maximum effective NPY dose (10 μg), the net increase in size of the first meal after injection was similar in old weight-stable (presenescent) and young rats (10.85 ± 1.73 and 12.63 ± 2.52 g/kg body wt0.67, respectively). In contrast, senescent rats that had spontaneously lost ∼10% of body weight had significantly lower net increases at their first post-NPY meal (1.33 ± 0.33 g/kg body wt0.67) than before they began losing weight. Thus altered feeding responses to NPY occur in aging rats concomitantly with spontaneous decrements in food intake and body weight near the end of life.

Effect of aging on urinary concentrating mechanism and vasopressin-dependent cAMP in rats

1982 ◽  
Vol 243 (2) ◽  
pp. F121-F125 ◽  
Author(s):  
N. Beck ◽  
B. P. Yu
Keyword(s):  
Free Access ◽  
Fischer 344 Rats ◽  
Renal Papilla ◽  
Camp Concentration ◽  
Fischer 344 ◽  
Camp Generation ◽  
Low Concentrations ◽  
Old Rats ◽  
Urinary Concentrating Ability ◽  
The Right

The effect of aging on urinary concentrating ability and the pathogenic mechanism involved were investigated in Fischer 344 rats. While the rats had free access to drinking water, 24-mo-old rats were polydipsic and polyuric compared with 6- and 12-mo-old rats. The maximum urinary concentrating ability after 40-58 h of water deprivation was not different between 6- and 12-mo-old rats (Uosmol 2,941 +/- 173 vs. 2,706 +/- 96 (SE) mosmol/kg), but it was significantly decreased in 24-mo-old rats (1,885 +/- 172 mosmol/kg, P less than 0.01). Similarly, although 5 mU/ml vasopressin increased the concentration of cAMP and papillary slices in 12-mo-old rats (delta +2.81 +/- 0.62 pmol/mg tissue, P less than 0.01), the same concentration of vasopressin failed to increase the cAMP concentration in 24-mo-old rats (delta +0.25 +/- 0.21 pmol/mg tissue, P greater than 0.05). In the adenylate cyclase preparation of renal papilla, the response to low concentrations of vasopressin was diminished in 24-mo-old rats. The dose-response curve was shifted to the right and the ED50 concentration of vasopressin was increased in 24-mo-old rats compared with 12-mo-old rats: 1.40 +/- 0.12 mU/ml vasopressin vs. 3.04 +/- 0.22. These results suggest that the decrease in vasopressin-dependent cAMP generation may in part be responsible for the impairment of urinary concentrating ability in 24-mo-old rats.

Effect of age and dietary calcium on renal 25(OH)D metabolism, serum 1,25(OH)2D, and PTH

1984 ◽  
Vol 246 (3) ◽  
pp. E266-E270 ◽  
Author(s):  
H. J. Armbrecht ◽  
L. R. Forte ◽  
B. P. Halloran
Keyword(s):  
Vitamin D ◽  
Fischer 344 Rats ◽  
Serum Ipth ◽  
Fischer 344 ◽  
Age Related ◽  
Old Rats ◽  
Intestinal Ca Absorption ◽  
Effect Of Age ◽  
Cortical Slices

The purpose of this study was to determine how serum 1,25(OH)2D, renal production of [3H]1,25(OH)2D and [3H]24,25(OH)2D from [3H]25(OH)D, and serum IPTH change with age and dietary Ca restriction. Male Fischer 344 rats aged 3, 13, and 25 mo were placed on either a high-Ca (1.2%) or low-Ca (0.02%) vitamin D-replete diet. After 4 wk, serum was collected, and renal conversion of [3H]25(OH)D3 to [3H]1,25(OH)2D3 and [3H]24,25(OH)2D3 was measured in vitro using isolated renal cortical slices. Serum 1,25(OH)2D and renal [3H]1,25(OH)2D3 production were markedly reduced in 13- and 25-mo-old rats compared with 3-mo-old rats fed the low-Ca diet. In 3-mo-old rats, feeding the low-Ca diet increased serum 1,25(OH)2D by 18-fold and renal [3H]1,25(OH)2D3 production by threefold compared with feeding the high-Ca diet. In 25-mo-old rats, dietary Ca had no effect on these parameters. Renal [3H]24,25(OH)2D3 production was increased in the 13- and 25-mo-old rats compared with the 3-mo-old rats. Serum IPTH increased with age regardless of diet and was significantly increased by the low-Ca diet in 3-mo but not in 13- or 25-mo-old rats. The changes in serum 1,25(OH)2D and renal [3H]1,25(OH)2D3 production observed in this study may account for the previously observed age-related decline in intestinal Ca absorption in this animal model.

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