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.

scholarly journals Electromyographic activation patterns during swallowing in older adults

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jin Young Ko ◽  
Hayoung Kim ◽  
Joonyoung Jang ◽  
Jun Chang Lee ◽  
Ju Seok Ryu
Keyword(s):  
Older Adults ◽  
Viscous Fluid ◽  
Muscle Activation ◽  
Fatty Infiltration ◽  
Liquid Volume ◽  
Type I ◽  
Type Ii ◽  
Activation Patterns ◽  
Muscle Activation Patterns ◽  
Age Related

AbstractAge-related weakness due to atrophy and fatty infiltration in oropharyngeal muscles may be related to dysphagia in older adults. However, little is known about changes in the oropharyngeal muscle activation pattern in older adults. This was a prospective and experimental study. Forty healthy participants (20 older [> 60 years] and 20 young [< 60 years] adults) were enrolled. Six channel surface electrodes were placed over the bilateral suprahyoid (SH), bilateral retrohyoid (RH), thyrohyoid (TH), and sternothyroid (StH) muscles. Electromyography signals were then recorded twice for each patient during swallowing of 2 cc of water, 5 cc of water, and 5 cc of a highly viscous fluid. Latency, duration, and peak amplitude were measured. The activation patterns were the same, in the order of SH, TH, and StH, in both groups. The muscle activation patterns were classified as type I and II; the type I pattern was characterized by a monophasic shape, and the type II comprised a pre-reflex phase and a main phase. The oropharyngeal muscles and SH muscles were found to develop a pre-reflex phase specifically with increasing volume and viscosity of the swallowed fluid. Type I showed a different response to the highly viscous fluid in the older group compared to that in the younger group. However, type II showed concordant changes in the groups. Therefore, healthy older people were found to compensate for swallowing with a pre-reflex phase of muscle activation in response to increased liquid volume and viscosity, to adjust for age-related muscle weakness.

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.

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.

scholarly journals Intradermal angiotensin II administration attenuates the local cutaneous vasodilator heating response

2008 ◽  
Vol 295 (1) ◽  
pp. H327-H334 ◽  
Author(s):  
Julian M. Stewart ◽  
Indu Taneja ◽  
Neeraj Raghunath ◽  
Debbie Clarke ◽  
Marvin S. Medow
Keyword(s):  
Angiotensin Ii ◽  
Healthy Volunteers ◽  
Local Heating ◽  
Ringer Solution ◽  
Sodium Ascorbate ◽  
Ang Ii ◽  
Postural Tachycardia ◽  
Graded Responses ◽  
Heat Response ◽  
Dose Responses

The vasodilation response to local cutaneous heating is nitric oxide (NO) dependent and blunted in postural tachycardia but reversed by angiotensin II (ANG II) type 1 receptor (AT1R) blockade. We tested the hypothesis that a localized infusion of ANG II attenuates vasodilation to local heating in healthy volunteers. We heated the skin of a calf to 42°C and measured local blood flow to assess the percentage of maximum cutaneous vascular conductance (%CVCmax) in eight healthy volunteers aged 19.5–25.5 years. Initially, two experiments were performed; in one, Ringer solution was perfused in three catheters, the response to heating was measured, 2 μg/l losartan, 10 mM nitro-l-arginine (NLA), or NLA + losartan was added to perfusate, and the heat response was remeasured; in another, 10 μM ANG II was given, the heat response was measured, losartan, NLA, or NLA + losartan was added to ANG II, and the heat response was reassessed. The heat response decreased with ANG II, particularly the plateau phase (47 ± 5 vs. 84 ± 3 %CVCmax). Losartan increased baseline conductance in both experiments (from 8 ± 1 to 20 ± 2 and 12 ± 1 to 24 ± 3). Losartan increased the ANG II response (83 ± 4 vs. 91 ± 6 in Ringer). NLA decreased both angiotensin and Ringer responses (31 ± 4 vs. 43 ± 3). NLA + losartan blunted the Ringer response (48 ± 2), but the ANG II response (74 ± 5) increased. In a second set of experiments, we used dose responses to ANG II (0.1 nM to 10 μM) with and without NLA + losartan to confirm graded responses. Sodium ascorbate (10 mM) restored the ANG II-blunted heating plateau. NO synthase and AT1R inhibition cause an NO-independent angiotensin-mediated vasodilation with local heating. ANG II mediates the AT1R blunting of local heating, which is not exclusively NO dependent, and is improved by antioxidant supplementation.

Angiotensin II type I receptor blockade attenuates reflex cutaneous vasoconstriction in aged but not young skin

2015 ◽  
Vol 308 (10) ◽  
pp. H1215-H1220 ◽  
Author(s):  
James A. Lang ◽  
Kelsey E. Kolb
Keyword(s):  
Angiotensin Ii ◽  
Rho Kinase ◽  
Whole Body ◽  
Type I ◽  
Older Individuals ◽  
Forearm Skin ◽  
Lactated Ringer's Solution ◽  
Body Cooling ◽  
Whole Body Cooling ◽  
Doppler Flux

Stimulation of angiotensin II type I receptors (AT1R) elicits vasoconstriction (VC) that may be occurring through the activation of a pathogenic vascular pathway such as Rho kinase (ROCK). We hypothesize that reflex cutaneous VC to whole body cooling (mean skin temperature = 30.5°C) in older humans relies in part on AT1R activation, which may explain greater ROCK activity attendant with aging. Two microdialysis (MD) fibers were placed in the forearm skin of 10 young (Y; 24 ± 1 yr) and 10 older (O; 70 ± 2 yr) individuals for infusion of 1) lactated Ringer's solution (switched to fasudil, a ROCK antagonist, after cooling); and 2) AT1R blockade with losartan. Laser Doppler flux (LDF) was measured over each MD site and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/mean arterial pressure) and expressed as percent change from baseline (%ΔCVCBASELINE). In older individuals the VC response to whole body cooling was blunted (Y = −34 ± 2, O = −17 ± 3%ΔCVC) and was further attenuated at the losartan site (Y = −34 ± 3, O = −9 ± 3%ΔCVC; P < 0.05). The VC response to an exogenous 10-μM dose of angiotensin II (Y = −27 ± 3, O = −42 ± 5%ΔCVC) was completely blocked in sites pretreated with losartan or with fasudil. These data suggest that AT1R activation contributes to the reflex VC response in aged but not young skin. Furthermore, the angiotensin II component of the VC response appears to occur primarily through a ROCK-mediated mechanism.

scholarly journals Selected Contribution: Gender differences in the endothelin-B receptor contribution to basal cutaneous vascular tone in humans

2001 ◽  
Vol 91 (5) ◽  
pp. 2407-2411 ◽  
Author(s):  
D. L. Kellogg ◽  
Y. Liu ◽  
P. E. Pérgola
Keyword(s):  
Laser Doppler Flowmetry ◽  
Vascular Tone ◽  
Ringer Solution ◽  
Laser Doppler ◽  
Doppler Flowmetry ◽  
Forearm Skin ◽  
Endothelin B ◽  
Cutaneous Vascular Conductance ◽  
Male Subjects ◽  
Female Subjects

To test whether the contribution of endothelin-B (ET-B) receptors to resting vascular tone differs between genders, we administered the ET-B receptor antagonist BQ-788 into the forearm skin of 11 male and 11 female subjects by intradermal microdialysis. Skin blood flow was measured using laser-Doppler flowmetry at the microdialysis site. The probe was perfused with Ringer solution alone, followed by BQ-788 (150 nM) and finally sodium nitroprusside (28 mM) to effect maximal cutaneous vasodilation. Cutaneous vascular conductance (CVC) was calculated (laser-Doppler flowmetry/mean arterial pressure) and normalized to maximal levels (%max). In male subjects, baseline CVC was (mean ± SE) 19 ± 3%max and increased to 26 ± 5%max with BQ-788 ( P < 0.05 vs. baseline). In female subjects, baseline CVC was 13 ± 1%max and decreased to 10 ± 1%max in response to BQ-788. CVC responses to BQ-788 differed with gender ( P < 0.05); thus the contribution of ET-B receptors to resting cutaneous vascular tone differs between men and women. In men, ET-B receptors mediate tonic vasoconstriction, whereas, in women, ET-B receptors mediate tonic vasodilation.

Prostanoids contribute to cutaneous active vasodilation in humans

2006 ◽  
Vol 291 (3) ◽  
pp. R596-R602 ◽  
Author(s):  
Gregg R. McCord ◽  
Jean-Luc Cracowski ◽  
Christopher T. Minson
Keyword(s):  
Core Body Temperature ◽  
Local Heating ◽  
Ringer Solution ◽  
Control Site ◽  
Whole Body ◽  
Nitric Oxide Synthase Inhibitor ◽  
Doppler Flowmetry ◽  
Forearm Skin ◽  
Synthase Inhibitor ◽  
Hyperemic Response

The specific mechanisms by which skin blood flow increases in response to a rise in core body temperature via cutaneous active vasodilation are poorly understood. The primary purpose of this study was to determine whether the cyclooxygenase (COX) pathway contributes to active vasodilation during whole body heat stress ( protocol 1; n = 9). A secondary goal was to verify that the COX pathway does not contribute to the cutaneous hyperemic response during local heating ( protocol 2; n = 4). For both protocols, four microdialysis fibers were placed in forearm skin. Sites were randomly assigned and perfused with 1) Ringer solution (control site); 2) ketorolac (KETO), a COX-1/COX-2 pathway inhibitor; 3) NG-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor; and 4) a combination of KETO and l-NAME. During the first protocol, active vasodilation was induced using whole body heating with water-perfused suits. The second protocol used local heaters to induce a local hyperemic response. Red blood cell flux (RBC flux) was indexed at all sites using laser-Doppler flowmetry, and cutaneous vascular conductance (CVC; RBC flux/mean arterial pressure) was normalized to maximal vasodilation at each site. During whole body heating, CVC values at sites perfused with KETO (43 ± 9% CVCmax), l-NAME (35 ± 9% CVCmax), and combined KETO/l-NAME (22 ± 8% CVCmax) were significantly decreased with respect to the control site (59 ± 7% CVCmax) ( P < 0.05). Additionally, CVC at the combined KETO/l-NAME site was significantly decreased compared with sites infused with KETO or l-NAME alone ( P < 0.05). In the second protocol, the hyperemic response to local heating did not differ between the control site and KETO site or between the l-NAME and KETO/l-NAME site. These data suggest that prostanoids contribute to active vasodilation, but do not play a role during local thermal hyperemia.

scholarly journals MFAP4 Deficiency Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm Formation Through Regulation of Macrophage Infiltration and Activity

2021 ◽  
Vol 8 ◽  
Author(s):  
Bartosz Pilecki ◽  
Paulo V. S. D. de Carvalho ◽  
Katrine L. Kirketerp-Møller ◽  
Anders Schlosser ◽  
Karin Kejling ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Apolipoprotein E ◽  
Macrophage Infiltration ◽  
Elastic Membrane ◽  
Ang Ii ◽  
Monocyte Migration ◽  
Age Related ◽  
Abdominal Aortic

Objective: Abdominal aortic aneurysm (AAA) is a common age-related vascular disease characterized by progressive weakening and dilatation of the aortic wall. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix (ECM) protein involved in the induction of vascular remodeling. This study aimed to investigate if MFAP4 facilitates the development of AAA and characterize the underlying MFAP4-mediated mechanisms.Approach and Results: Double apolipoprotein E- and Mfap4-deficient (ApoE−/−Mfap4−/−) and control apolipoprotein E-deficient (ApoE−/−) mice were infused subcutaneously with angiotensin II (Ang II) for 28 days. Mfap4 expression was localized within the adventitial and medial layers and was upregulated after Ang II treatment. While Ang II-induced blood pressure increase was independent of Mfap4 genotype, ApoE−/−Mfap4−/− mice exhibited significantly lower AAA incidence and reduced maximal aortic diameter compared to ApoE−/− littermates. The ApoE−/−Mfap4−/− AAAs were further characterized by reduced macrophage infiltration, matrix metalloproteinase (MMP)-2 and MMP-9 activity, proliferative activity, collagen content, and elastic membrane disruption. MFAP4 deficiency also attenuated activation of integrin- and TGF-β-related signaling within the adventitial layer of AAA tissues. Finally, MFAP4 stimulation promoted human monocyte migration and significantly upregulated MMP-9 activity in macrophage-like THP-1 cells.Conclusion: This study demonstrates that MFAP4 induces macrophage-rich inflammation, MMP activity, and maladaptive remodeling of the ECM within the vessel wall, leading to an acceleration of AAA development and progression. Collectively, our findings suggest that MFAP4 is an essential aggravator of AAA pathology that acts through regulation of monocyte influx and MMP production.

scholarly journals Effect of Angiotensin II on Chondrocyte Degeneration and Protection via Differential Usage of Angiotensin II Receptors

2021 ◽  
Vol 22 (17) ◽  
pp. 9204
Author(s):  
Takashi Nishida ◽  
Sho Akashi ◽  
Masaharu Takigawa ◽  
Satoshi Kubota
Keyword(s):  
Articular Cartilage ◽  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Cartilage Degeneration ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Age Related ◽  
Proliferation And Differentiation

The renin–angiotensin system (RAS) controls not only systemic functions, such as blood pressure, but also local tissue-specific events. Previous studies have shown that angiotensin II receptor type 1 (AT1R) and type 2 (AT2R), two RAS components, are expressed in chondrocytes. However, the angiotensin II (ANG II) effects exerted through these receptors on chondrocyte metabolism are not fully understood. In this study, we investigated the effects of ANG II and AT1R blockade on chondrocyte proliferation and differentiation. Firstly, we observed that ANG II significantly suppressed cell proliferation and glycosaminoglycan content in rat chondrocytic RCS cells. Additionally, ANG II decreased CCN2, which is an anabolic factor for chondrocytes, via increased MMP9. In Agtr1a-deficient RCS cells generated by the CRISPR-Cas9 system, Ccn2 and Aggrecan (Acan) expression increased. Losartan, an AT1R antagonist, blocked the ANG II-induced decrease in CCN2 production and Acan expression in RCS cells. These findings suggest that AT1R blockade reduces ANG II-induced chondrocyte degeneration. Interestingly, AT1R-positive cells, which were localized on the surface of the articular cartilage of 7-month-old mice expanded throughout the articular cartilage with aging. These findings suggest that ANG II regulates age-related cartilage degeneration through the ANG II–AT1R axis.

Influence of age on glomerular binding of angiotensin II in normotensive and spontaneously hypertensive rats

1989 ◽  
Vol 76 (6) ◽  
pp. 619-623 ◽  
Author(s):  
E. A. Messenger ◽  
C. Stonier ◽  
G. M. Aber
Keyword(s):  
Angiotensin Ii ◽  
Spontaneously Hypertensive Rats ◽  
Plasma Renin ◽  
Affinity Constant ◽  
Ang Ii ◽  
Shr Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Age Related ◽  
Age Related Changes

1. Glomerular angiotensin II (ANG II) binding has been studied in normotensive (NTR) and spontaneously hypertensive (SHR) rats at 5, 10, 15 and 20 weeks of age. 2. Binding of 125I-labelled ANG II by glomeruli from NTR and SHR was similar at 5 and 10 weeks of age, with 5 week values of 426.4 (range 384-469) and 400.2 ± 245 fmol/mg of protein; however, at 15 and 20 weeks ANG II binding by SHR glomeruli was significantly greater than by NTR, with 20 week values of 614.7 ± 245 and 308.3 ± 31.8 fmol/mg of protein, respectively (P < 0.01). 3. The ANG II binding affinity constant (Ka) of glomeruli from NTR and SHR was comparable at 5, 10 and 15 weeks of age, with values of 1.5 (range 1.1-1.9) and 1.08 ± 0.35 nmol/l, respectively, at 5 weeks; whereas at 20 weeks the Ka for SHR glomeruli was significantly greater than for NTR, with values of 1.85 ± 0.45 and 0.66 ± 0.22 nmol/l, respectively (P < 0.001). 4. Age-related changes in glomerular binding of ANG II in SHR were not found to be related to changes in either plasma renin activity or systolic blood pressure.

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