Angiotensin II enhances β-adrenergic receptor-mediated vasorelaxation in aortas from young but not old rats

2000 ◽  
Vol 279 (6) ◽  
pp. H2807-H2814 ◽  
Author(s):  
William E. Schutzer ◽  
Hong Xue ◽  
John F. Reed ◽  
Jean-Baptiste Roullet ◽  
Sharon Anderson ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Adrenergic Receptor ◽  
Age Groups ◽  
Ang Ii ◽  
Camp Production ◽  
Fischer 344 ◽  
Age Related ◽  
Old Rats ◽  
Potent Vasoconstrictor ◽  
Direct Activator

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.

scholarly journals Age-related differences in the cutaneous vascular response to exogenous angiotensin II

2019 ◽  
Vol 316 (3) ◽  
pp. H516-H521
Author(s):  
James A. Lang ◽  
Alex C. Krajek
Keyword(s):  
Older Adults ◽  
Angiotensin Ii ◽  
Ringer Solution ◽  
Control Site ◽  
Laser Doppler ◽  
Type Ii ◽  
Ang Ii ◽  
Age Related ◽  
Forearm Skin ◽  
Doppler Flux

Angiotensin II (ANG II) is locally produced in human skin and contributes to the reflex vasoconstriction (VC) response in aged but not young skin. We hypothesized that the exogenous ANG II-mediated VC response would be greater in older adults and would be affected by inhibition of adrenoreceptor or ANG II type II receptor (AT2R) pathways. Three microdialysis (MD) fibers were placed in the forearm skin of 11 young (26 ± 3 yr) and 11 older (68 ± 4 yr) individuals for perfusion of 1) Ringer solution (control), 2) adrenoreceptor blockade with yohimbine + propranolol, and 3) AT2R inhibition with PD-123319. ANG II was then added to the perfusates at eight graded dose concentrations ranging from 10−10 to 10−3 M. Laser Doppler flux was measured at each MD site, and cutaneous vascular conductance (CVC) was calculated as CVC =  laser Doppler flux/mean arterial pressure and normalized to baseline CVC values collected before ANG II perfusion (%ΔCVCbaseline). At the control site, older adults (−34 ± 4%ΔCVCbaseline) exhibited a greater peak VC compared with young adults (−22 ± 2%ΔCVCbaseline, P < 0.05), which was attenuated with adrenoreceptor blockade. Young skin exhibited a vasodilation in response to lower ANG II doses that was inhibited with AT2R inhibition. AT2R inhibition also increased the VC response to higher ANG II doses such that young skin responded similarly to older skin. These results indicate that ANG II has a greater VC influence in older than young individuals. Furthermore, ANG II may be affecting multiple targets, including adrenergic and AT2R pathways. NEW & NOTEWORTHY Intradermal perfusion of successive doses of angiotensin II (ANG II) revealed a role for ANG II type II receptors and dose-dependent, ANG II-mediated vasodilation in young but not older adults. In contrast, older adults exhibited greater vasoconstriction for a given dose of ANG II. The increased vasoconstriction in older adults was subsequently blunted with adrenoreceptor blockade, which indicates an interaction between ANG II and adrenergic signaling pathways in the cutaneous microcirculation.

Age-dependent activation of PKC isoforms by angiotensin II in the proximal nephron

2001 ◽  
Vol 281 (3) ◽  
pp. R861-R867 ◽  
Author(s):  
Dianne M. Boesch ◽  
Jeffrey L. Garvin
Keyword(s):  
Specific Binding ◽  
Age Groups ◽  
Proximal Tubules ◽  
Ang Ii ◽  
Fluid Absorption ◽  
Adult Rats ◽  
Young Rats ◽  
Age Related ◽  
Pkc Isoforms ◽  
Pkc Β

ANG II increases fluid absorption in proximal tubules from young rats more than those from adult rats. ANG II increases fluid absorption in the proximal nephron, in part, via activation of protein kinase C (PKC). However, it is unclear how age-related changes in ANG II-induced stimulation of the PKC cascade differ as an animal matures. We hypothesized that the response of the proximal nephron to ANG II decreases as rats mature due to a reduction in the amount and activation of PKC rather than a decrease in the number or affinity of ANG II receptors. Because PKC translocates from the cytosol to the membrane when activated, we first measured PKC activity in the soluble and particulate fractions of proximal tubule homogenates exposed to vehicle or 10−10 M ANG II from young (26 ± 1 days old) and adult rats (54 ± 1 days old). ANG II increased PKC activity to the same extent in homogenates from young rats (from 0.119 ± 0.017 to 0.146 ± 0.015 U/mg protein) ( P < 0.01) and adult rats (from 0.123 ± 0.020 to 0.156 ± 0.023 U/mg protein) ( P < 0.01). Total PKC activity did not differ between groups (0.166 ± 0.018 vs. 0.181 ± 0.023). We next investigated whether activation of the α-, β-, and γ-PKC isoforms differed by Western blot. In homogenates from young rats, ANG II significantly increased activated PKC-α from 40.2 ± 6.5 to 60.2 ± 9.5 arbitrary units (AU) ( P < 0.01) but had no effect in adult rats (46.1 ± 5.1 vs. 48.5 ± 8.2 AU). Similarly, ANG II increased activated PKC-γ in proximal tubules from young rats from 47.9 ± 13.2 to 65.6 ± 16.7 AU ( P < 0.01) but caused no change in adult rats. Activated PKC-β, however, increased significantly in homogenates from both age groups. Specifically, activated PKC-β increased from 8.6 ± 1.4 to 12.2 ± 2.1 AU ( P < 0.01) in homogenates from nine young rats and from 19.0 ± 5.5 to 25.1 ± 7.1 AU ( P < 0.01) in homogenates from 12 adult rats. ANG II did not alter the amount of soluble PKC-α, -β, and -γ significantly. The total amount of PKC-α and -γ did not differ between homogenates from young and adult rats, whereas the total amount of PKC-β was 59.7 ± 10.7 and 144.9 ± 41.8 AU taken from young and adult rats, respectively ( P < 0.05). Maximum specific binding and affinity of ANG II receptors were not significantly different between young and adult rats. We concluded that the primary PKC isoform activated by ANG II changes during maturation.

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
Keyword(s):  
Electrical Stimulation ◽  
Age Groups ◽  
Circular Muscle ◽  
Colonic Transit ◽  
Maximum Response ◽  
Suitable Model ◽  
Fischer 344 ◽  
Age Related ◽  
Muscle Histology

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.

Longitudinal force and stress of rat's esophagus: age-related changes.

1977 ◽  
Vol 232 (6) ◽  
pp. E580
Author(s):  
M P Zabinski ◽  
P Biancani
Keyword(s):  
Age Groups ◽  
Longitudinal Direction ◽  
Longitudinal Force ◽  
Active Stress ◽  
Length Relationship ◽  
Age Related ◽  
Old Rats ◽  
The Difference

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.

Glutathione metabolism in heart and liver of the aging rat

1994 ◽  
Vol 72 (1-2) ◽  
pp. 58-61 ◽  
Author(s):  
M. Stio ◽  
T. Iantomasi ◽  
F. Favilli ◽  
P. Marraccini ◽  
B. Lunghi ◽  
...  
Keyword(s):  
Rat Heart ◽  
Reduced Glutathione ◽  
Age Groups ◽  
Glutathione Metabolism ◽  
Oxidized Glutathione ◽  
Glutathione S Transferase ◽  
Age Related ◽  
Glutamylcysteine Synthetase ◽  
Old Rats ◽  
Glucose 6 Phosphate Dehydrogenase

A comprehensive study on glutathione metabolism in rat heart and liver as a function of age was performed. In the heart, reduced glutathione, total glutathione, and the glutathione redox index showed a decrease during aging, while oxidized glutathione levels increased in 5-month-old rats with respect to the young animals and remained quite constant in 14- and 27-month-old rats. In the liver, the highest levels of reduced glutathione were found in the 2-month-old rats, while oxidized glutathione reached a peak at 5 months. Glutathione-associated enzymes showed age-related changes. Glutathione peroxidase, unaffected by aging in the heart, decreased in the liver of the 27-month-old rats. In the heart and the liver, the highest values of glutathione S-transferase were found at 5 months and 27 months, respectively. Glucose-6-phosphate dehydrogenase followed a similar trend in both heart and liver. Glutathione reductase also showed the same behaviour in heart and in liver, increasing in old rats with respect to the other age groups. A decrease in γ-glutamylcysteine synthetase was found in the heart and liver of 27-month-old rats in comparison with the 2-month-old ones. In conclusion, a decreased antioxidant capability has been demonstrated in both heart and liver of old rats.Key words: glutathione metabolism, age, rat heart, rat liver.

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.

Circulating hyaluronan levels in the rodent: effects of age and diet

1995 ◽  
Vol 268 (4) ◽  
pp. C952-C957 ◽  
Author(s):  
J. Yannariello-Brown ◽  
S. H. Chapman ◽  
W. F. Ward ◽  
T. C. Pappas ◽  
P. H. Weigel
Keyword(s):  
Fish Meal ◽  
Caloric Intake ◽  
Protein Source ◽  
Male Rats ◽  
Semisynthetic Diet ◽  
Fischer 344 ◽  
Age Related ◽  
Old Rats ◽  
Ad Libitum ◽  
Age Related Changes

Circulating hyaluronan (HA) levels were investigated as a function of age and diet in Fischer 344 male rats. A biphasic pattern of age-related changes was observed in rats fed ad libitum a diet in which the protein source was soya/fish meal. HA levels in 3- to 6- and 22- to 29-mo-old rats were not statistically different. However, HA levels in 12- to 20-mo-old rats were 10-29% of the levels in younger or aged adults. HA levels were also measured in rats fed ad libitum a semisynthetic diet in which the protein source was hydrolyzed casein. Whereas the two colonies exhibited similar biphasic age-related changes, HA levels differed 4- to 20-fold at every age examined. Caloric restriction affected HA levels in 19-mo-old casein-fed rats; HA levels were 2.3 times higher than age-matched controls and were not statistically different from young or aged animals. Serum and plasma HA levels were identical in the same individuals at all ages tested. These data suggest that HA turnover and metabolism in the rat are affected by age, dietary composition, and caloric intake.

Losartan inhibits STAT1 activation and protects human glomerular mesangial cells from angiotensin II induced premature senescence

2012 ◽  
Vol 90 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Sumin Jiao ◽  
Xiaoyu Zheng ◽  
Xue Yang ◽  
Jin Zhang ◽  
Lining Wang
Keyword(s):  
Angiotensin Ii ◽  
Mesangial Cells ◽  
Morphological Changes ◽  
Positive Staining ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Cycle Arrest ◽  
Age Related ◽  
Elevated Expression ◽  
Human Glomerular Mesangial Cells

Human glomerular mesangial cells (HMCs) have a finite lifespan, and eventually enter irreversible growth arrest known as cellular senescence, which is thought to contribute to kidney ageing and age-related kidney disorders, such as chronic kidney disease. The signal transducer and activator of transcription 1 (STAT1) is a latent transcription factor involved in a variety of signal transduction pathways, including cell proliferation, apoptosis, and differentiation, but whether it could regulate HMC senescence still remains to be explored. In our study, the induction of angiotensin II (Ang II)-accelerated HMC senescence, as judged by increased senescence-associated β-galactosidase (SA-β-gal)-positive staining cells, morphological changes, and G0/G1 cell cycle arrest. STAT1 activity and the expression of p53 and p21Cip1 were increased after Ang II treatment. STAT1 knockdown using RNA interference significantly inhibited the progression of HMC senescence and decreased the elevated expression of p53 and p21Cip1. Pretreating HMCs with Ang II receptor blocker losartan also inhibited the progression of HMC senescence and STAT1 activity. Our results indicate that STAT1 is implicated in the mediation of Ang II-induced HMC senescence through p53/ p21Cip1 pathway, and that losartan could attenuate HMC senescence by regulating STAT1. The antioxidant N-acetyl-L-cysteine reduced ROS production and STAT1 activity induced by Ang II, indicating that Ang II uses ROS as a second messenger to regulate STAT1 activity.

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