Effects of age on muscarinic cholinergic receptors in rat myocardium

1983 ◽  
Vol 61 (8) ◽  
pp. 822-829 ◽  
Author(s):  
Njanoor Narayanan ◽  
Jo-Anne Derby
Keyword(s):  
Young Adult ◽  
Muscarinic Receptor ◽  
Muscarinic Receptors ◽  
Specific Binding ◽  
Ventricular Myocardium ◽  
Aged Rats ◽  
Adult Rats ◽  
Related Difference ◽  
Age Related ◽  
Receptor Sites

Atrial and ventricular myocardium from young (3–4 months old), young adult (7–8 months old), and aged (24–25 months old) rats were used to study the influence of age on cardiac cholinergic muscarinic receptors. The density of muscarinic receptors (expressed as fmol/mg protein or pmol/g tissue), determined by the specific binding of [3Hjquinuclidinyl benzyl ate ([3H]QNB), was significantly greater (24–29%) in atria of aged rats compared with that in atria of young or young adult rats. The muscarinic receptor density in ventricles was found to be essentially similar in all age groups studied. Antagonist as well as agonist binding characteristics of muscarinic receptor sites were examined in atria and ventricles from young and aged rats. No significant age-related difference was observed in the dissociation constant (KD) of atrial or ventricular receptors for the antagonist ligand [3H]QNB (KD apparent (nM): 1.04 ± 0.16 and 0.91 ± 0.12, respectively, for young and aged atria; 0.75 ± 0.08 and 0.76 ± 0.10, respectively, for young and aged ventricles). Similarly, the concentrations of muscarinic antagonist atropine and agonist carbachol causing 50% inhibition of [3H]QNB binding to the receptor sites (IC50) in atria and ventricles were not altered by age. Age-related difference was also not evident in the Hill coefficients for [3H]QNB, atropine, and carbachol. These results indicate that diminished responsiveness of the aged heart to vagal stimulation and exogenously administered cholinergic agents reported in the literature cannot be attributed to an age-related reduction in the number of cardiac muscarinic receptors or their affinities toward agonist or antagonist ligands.

Enhanced chronotropic and inotropic responses of rat myocardium to cholinergic stimulus with aging

1992 ◽  
Vol 70 (12) ◽  
pp. 1618-1624 ◽  
Author(s):  
Na Su ◽  
Njanoor Narayanan
Keyword(s):  
Muscarinic Receptor ◽  
Heart Function ◽  
Specific Binding ◽  
Adrenergic Stimulation ◽  
Chronotropic Response ◽  
Related Difference ◽  
Age Related ◽  
Rat Hearts ◽  
Inotropic Responses ◽  
The Impact

The ability of the heart to respond to adrenergic stimulation diminishes with aging, and this may be one of the factors contributing to the age-associated decline in cardiac stress responsiveness. On the other hand, little is known about the impact of aging on the responsiveness of the heart to cholinergic stimulation. In this study, we determined the chronotropic and inotropic responses of the isolated, Langendorff-perfused hearts from adult (6–8 months) and aged (28–30 months) rats to cholinergic agonists so as to assess age-related alterations in postsynaptic cholinergic control of heart function. The results showed the following. (i) In isolated perfused spontaneously beating rat hearts, the negative chronotropic response to acetylcholine (10−9–10−5 M) was up to 4-fold greater in the aged compared with adult hearts; this age-related difference was less marked (2-fold) but not abolished in the presence of a maximally effective concentration (5 μM) of the cholinesterase inhibitor eserine. (ii) The cholinesterase-resistant agonist carbachol (10−9–2.5 × 10−6 M) elicited a 2- to 3-fold greater negative chronotropic response in the aged compared with adult hearts. (iii) In isolated perfused, electrically paced (4 Hz) rat hearts, carbachol (10−9–10−3 M) elicited a concentration-dependent negative inotropic response, which was 2-fold greater in the aged compared with adult heart at all carbachol concentrations, (iv) Acetylcholinesterase activities (micromoles per gram per hour) were 50–60% lower in the aged atria (83 ± 21) and ventricles (24 ± 6) than in adult atria (210 ± 20) and ventricles (47 ± 7). (v) No significant age-related difference was observed in the specific binding of (–)-[3H]quinuclidinyl benzilate to muscarinic receptor sites in atria or ventricles. These findings demonstrate a striking enhancement in the responses of the heart to cholinergic stimulus with aging, which can be attributed in part, but not solely to age-associated decline in cholinesterase activity. Age-associated alterations in muscarinic receptor linked events may also underlie the cholinergic hypersensitivity of the aging heart.Key words: aging, muscarinic receptor, cardiac performance in vitro, cholineresterase activity.

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.

M2 muscarinic ([3H]N-methyl scopolamine) binding in micropunches of rat ventricular myocardium: characterization and modification by progesterone

1992 ◽  
Vol 70 (7) ◽  
pp. 943-948 ◽  
Author(s):  
M. Wilkinson ◽  
Alice Giles ◽  
Diane A. Wilkinson
Keyword(s):  
Muscarinic Receptor ◽  
Cardiac Tissue ◽  
Specific Binding ◽  
Ventricular Myocardium ◽  
Water Soluble ◽  
Intact Cells ◽  
Muscarinic Binding Sites ◽  
Methyl Scopolamine

A new technique is outlined for the characterization and quantification of M2 muscarinic binding sites (receptors) in micro-punches (1 mm diam.), cut from slices (350 μm), of fresh cardiac tissue using the hydrophilic antagonist [3H]N-methyl scopolamine. The use of this water-soluble ligand allows us to label, and quantify, M2 receptors on the cell surface of intact cells contained within the micropunch. We believe that cardiac micropunches offer a simple but powerful approach to the investigation of membrane receptor regulation in tissue that largely retains the in vivo cytoarchitecture. Specific binding is reversible, stereospecific, saturable, of high affinity, and has the drug specificity typical of an M2 muscarinic receptor. In rat left ventricle, Bmax was 151.2 ± 10.3 fmol/mg protein while KD was 1.0 ± 0.1 nM. Nonspecific binding of the ligand was very low, varying from 2.8% (at 0.27 nM) to 7.7% (at 3.58 nM). This micropunch assay was used to determine that progesterone can compete with the muscarinic ligand for the M2 receptor in vitro (IC50 = 50 × 10−6 M). The steroids estradiol and testosterone, as well as ouabain, were without effect. Progesterone inhibited [3H]N-methyl scopolamine binding competitively (KD reduced from 1.9 to 4.3 nM) without affecting the rate of association of the ligand. However, progesterone induced a rapid dissociation of the ligand from its receptor. We conclude that the micropunch assay described here is suitable for the continued study of sex hormone effects on cardiac function.Key words: cardiac micropunches, muscarinic receptor, progesterone, [3H]N-methyl scopolamine.

Chronic β-agonist administration affects cardiac function of adult but not old rats, independent of β-adrenoceptor density

2005 ◽  
Vol 289 (1) ◽  
pp. H344-H349 ◽  
Author(s):  
Paul Gregorevic ◽  
James G. Ryall ◽  
David R. Plant ◽  
Martin N. Sillence ◽  
Gordon S. Lynch
Keyword(s):  
Cardiac Function ◽  
Contractile Function ◽  
Heart Function ◽  
Relative Increase ◽  
Left Ventricular ◽  
Aged Rats ◽  
Adult Rats ◽  
Age Related ◽  
Heart Mass

Although β-adrenoceptor agonists have clinical merit for attenuating the age-related loss of skeletal muscle mass and strength (sarcopenia), potential cardiac-related side effects may limit their clinical application. The aim of this study was to determine whether chronic β-agonist administration impairs cardiac function in adult or aged rats. Adult (16 mo) and aged (28 mo) Fischer 344 rats were treated with fenoterol (1.4 mg·kg−1·day−1 ip) or vehicle for 4 wk. Heart function was assessed in vitro before analyses of cardiac structure and β-adrenoceptor density. Heart mass increased 17% and 25% in fenoterol-treated adult and aged rats, respectively. The increased heart mass in aged, but not adult, rats was associated with a relative increase in collagen content. Cardiac hypertrophy in adult rats was associated with an increase in left ventricular developed pressure, a marked reduction in cardiac output, and a reduction in coronary flow per unit heart mass. In contrast, negligible differences in ventricular function were observed in fenoterol-treated aged rats. The differential effect on contractile function was not associated with age-related differences in β-adrenoceptor density but, rather, an age-related increase in downregulation after treatment. Our results show that chronic β-agonist treatment impairs cardiac function to a greater extent in adult than in aged rats. These results provide important information regarding the potential effects of chronic β-agonist use on cardiac function and the future development of safe and effective treatments for sarcopenia.

scholarly journals Para-chloroamphetamine (PCA)-induced ejaculation in aged rats, semen analysis and artificial insemination

1996 ◽  
Vol 30 (4) ◽  
pp. 332-336 ◽  
Author(s):  
Toru R. Saito ◽  
Ryoji Hokao ◽  
Yasumasa Wakafuji ◽  
Noriyuki Igarashi ◽  
Yoshio Agematsu ◽  
...  
Keyword(s):  
Young Adult ◽  
Sperm Motility ◽  
Artificial Insemination ◽  
Semen Analysis ◽  
Active Movement ◽  
Aged Rats ◽  
Adult Rats ◽  
Reproductive Ability ◽  
Sperm Counts ◽  
Old Rats

The present study was undertaken to determine sperm motility and counts in semen yielded by para-chloroamphetamine (PCA)-induced ejaculation of aged rats which had lost their reproductive ability, and to attempt artificial insemination with suspensions of spermatozoa obtained in this way. The semen yielded by PCA-induced ejaculation from aged (75-week-old) rats had average sperm counts of 0.82±0.69 × 107, which were much lower than the average counts (9.42±1.65 × 107) for semen spontaneously ejaculated by young adult rats (14 weeks old). However, 77.5% of the spermatozoa contained in the PCA-induced semen were rated as showing the most active movement. Spermatozoa collected in this way were injected into the upper parts of both uterine horns or into both ovarian bursae. Both methods made the females pregnant, but the results were better after injection into the ovarian bursae. The offspring born to these females showed no abnormalities.

scholarly journals Grape Powder Improves Age-Related Decline in Mitochondrial and Kidney Functions in Fischer 344 Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Indira Pokkunuri ◽  
Quaisar Ali ◽  
Mohammad Asghar
Keyword(s):  
Kidney Function ◽  
Kidney Injury ◽  
Protein Carbonyls ◽  
Aged Rats ◽  
Fischer 344 Rats ◽  
Adult Rats ◽  
Fischer 344 ◽  
Age Related ◽  
Kidney Injury Molecule 1 ◽  
Kidney Functions

We examined the effects and mechanism of grape powder- (GP-) mediated improvement, if any, on aging kidney function. Adult (3-month) and aged (21-month) Fischer 344 rats were treated without (controls) and with GP (1.5% in drinking water) and kidney parameters were measured. Control aged rats showed higher levels of proteinuria and urinary kidney injury molecule-1 (KIM-1), which decreased with GP treatment in these rats. Renal protein carbonyls (protein oxidation) and gp91phox-NADPH oxidase levels were high in control aged rats, suggesting oxidative stress burden in these rats. GP treatment in aged rats restored these parameters to the levels of adult rats. Moreover, glomerular filtration rate and sodium excretion were low in control aged rats suggesting compromised kidney function, which improved with GP treatment in aged rats. Interestingly, low renal mitochondrial respiration and ATP levels in control aged rats were associated with reduced levels of mitochondrial biogenesis marker MtTFA. Also, Nrf2 proteins levels were reduced in control aged rats. GP treatment increased levels of MtTFA and Nrf2 in aged rats. These results suggest that GP by potentially regulating Nrf2 improves aging mitochondrial and kidney functions.

Mechanical and histochemical characterization of skeletal muscles from senescent rats

1986 ◽  
Vol 251 (3) ◽  
pp. C421-C430 ◽  
Author(s):  
T. J. Eddinger ◽  
R. G. Cassens ◽  
R. L. Moss
Keyword(s):  
Young Adult ◽  
Fiber Type ◽  
Sodium Dodecyl ◽  
Age Groups ◽  
Isometric Tension ◽  
Test Method ◽  
Skinned Fibers ◽  
Shortening Velocity ◽  
Adult Rats ◽  
Age Related

Maximal shortening velocity (Vmax) and isometric tension (Po) were measured in living fiber bundles and skinned fibers from extensor digitorum longus (EDL) and soleus (SOL) muscles of young adult (9 mo) and senescent (30 mo) Fisher 344 rats. The fiber type composition of each muscle preparation was determined using myosin (M)-ATPase histochemistry. Vmax, determined by the slack test method, was unchanged in the EDL but was increased in the SOL muscles of young adult vs. senescent rats. Velocities determined at intermediate loads using the load-stepping technique were slower for EDL bundles but were nearly identical for SOL bundles from senescent vs. young adult rats. Po was greater in SOL and was unchanged in EDL bundles and skinned fibers from senescent vs. young adult rats. M-ATPase histochemistry and Vmax were in agreement for fast and slow muscle bundles and fibers. The relationship between tension and pCa (i.e.,--log[Ca2+]) in skinned fibers from each muscle was similar in both age groups. Sodium dodecyl sulfate-polyacrylamide gels of the skinned fibers consistently showed fast light chains (LCs) in the EDL fibers and slow LCs in the SOL fibers, with no apparent age-related differences.

scholarly journals Increased myogenic repressor Id mRNA and protein levels in hindlimb muscles of aged rats

2002 ◽  
Vol 282 (2) ◽  
pp. R411-R422 ◽  
Author(s):  
Stephen E. Alway ◽  
Hans Degens ◽  
Dawn A. Lowe ◽  
Gururaj Krishnamurthy
Keyword(s):  
Young Adult ◽  
Mrna Level ◽  
Brown Norway ◽  
Mrna Levels ◽  
Aged Rats ◽  
Adult Rats ◽  
Protein Levels ◽  
Fast And Slow Muscles ◽  
Hindlimb Muscles ◽  
Gastrocnemius Muscles

The objective of this study was to determine if levels of repressors to myogenic regulatory factors (MRFs) differ between muscles from young adult and aged animals. Total RNA from plantaris, gastrocnemius, and soleus muscles of Fischer 344 × Brown Norway rats aged 9 mo (young adult, n = 10) and 37 mo (aged, n = 10) was reverse transcribed and then amplified by PCR. To obtain a semiquantitative measure of the mRNA levels, PCR signals were normalized to cyclophilin or 18S signals from the corresponding reverse transcription product. Normalization to cyclophilin and 18S gave similar results. The mRNA levels of MyoD and myogenin were ∼275–650% ( P < 0.001) and ∼500–1,100% ( P < 0.001) greater, respectively, in muscles from aged compared with young adults. In contrast, the protein levels were lower in plantaris and gastrocnemius muscles and similar in the soleus muscle of aged vs. young adult rats. Id repressor mRNA levels were ∼300–900% greater in fast and slow muscles of aged animals ( P ≤ 0.02), and Mist 1 mRNA was ∼50% greater in the plantaris and gastrocnemius muscles ( P< 0.01). The mRNA level of Twist mRNA was not significantly affected by aging. Id-1, Id-2, and Id-3 protein levels were ∼17–740% greater ( P < 0.05) in hindlimb muscles of aged rats compared with young adult rats. The elevated levels of Id mRNA and protein suggest that MRF repressors may play a role in gene regulation of fast and slow muscles in aged rats.

Differential response of cardiac fibroblasts from young adult and senescent rats to ANG II

2003 ◽  
Vol 284 (4) ◽  
pp. H1454-H1459 ◽  
Author(s):  
K. Shivakumar ◽  
David E. Dostal ◽  
Kenneth Boheler ◽  
Kenneth M. Baker ◽  
Edward G. Lakatta
Keyword(s):  
Young Adult ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Receptor Subtype ◽  
Mrna Levels ◽  
Ang Ii ◽  
Adult Rats ◽  
Collagen Production ◽  
Age Related

The intracardiac ANG II-forming pathway is activated in the senescent myocardium, raising the possibility of enhanced ANG II effects on cardiac fibroblasts. This study established an in vitro model of cultured cardiac fibroblasts from aged rats to examine if the response of these cells to ANG II is modified in the aged heart. Levels of mRNA encoding renin, angiotensinogen, and the AT1 receptor subtype in cardiac fibroblasts from young adult and senescent rats were quantified by RT-PCR, net collagen production by a hydroxyproline-based assay, and transforming growth factor (TGF)-β levels using a commercial kit. In cardiac fibroblasts from young adult rats, ANG II significantly enhanced AT1mRNA levels, net collagen production, and TGF-β production. In fibroblasts from the aged myocardium, ANG II downregulated AT1 mRNA expression, had a less pronounced effect on net collagen production, and had no effect on TGF-β production. Such age-related modification of the response of cardiac fibroblasts to ANG II may counteract the effects of augmented intracardiac ANG II production in the senescent heart, limiting fibrogenesis.

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