scholarly journals Intermittent PTH 1–34 administration improves the marrow microenvironment and endothelium-dependent vasodilation in bone arteries of aged rats

2018 ◽  
Vol 124 (6) ◽  
pp. 1426-1437 ◽  
Author(s):  
Seungyong Lee ◽  
Ashley Bice ◽  
Brianna Hood ◽  
Juan Ruiz ◽  
Jahyun Kim ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Blood Vessels ◽  
Vascular Function ◽  
Dynamic Properties ◽  
Bone Microarchitecture ◽  
Fischer 344 ◽  
Young Rats ◽  
Nutrient Artery ◽  
Old Rats ◽  
Intermittent Pth

Inflammation coincides with diminished marrow function, vasodilation of blood vessels, and bone mass. Intermittent parathyroid hormone (PTH) administration independently improves marrow and vascular function, potentially impacting bone accrual. Currently, the influence of marrow and intermittent PTH administration on aged bone blood vessels has not been examined. Vasodilation of the femoral principal nutrient artery (PNA) was assessed in the presence and absence of marrow. Furthermore, we determined the influence of PTH 1–34 on 1) endothelium-dependent vasodilation and signaling pathways [i.e., nitric oxide (NO) and prostacyclin (PGI2)], 2) endothelium-independent vasodilation, 3) cytokine production by marrow cells, and 4) bone microarchitecture and bone static and dynamic properties. Young (4–6 mo) and old (22–24 mo) male Fischer-344 rats were treated with PTH 1–34 or a vehicle for 2 wk. In the absence and presence of marrow, femoral PNAs were given cumulative doses of acetylcholine, with and without the NO and PGI2blockers, and diethylamine NONOate. Marrow-derived cytokines and bone parameters in the distal femur were assessed. Exposure to marrow diminished endothelium-dependent vasodilation in young rats. Reduced bone volume and NO-mediated vasodilation occurred with old age and were partially reversed with PTH. Additionally, PTH treatment in old rats restored endothelium-dependent vasodilation in the presence of marrow and augmented IL-10, an anti-inflammatory cytokine. Endothelium-independent vasodilation was unaltered, and PTH treatment reduced osteoid surfaces in old rats. In conclusion, the marrow microenvironment reduced vascular function in young rats, and PTH treatment improved the marrow microenvironment and vasodilation with age.NEW & NOTEWORTHY This study investigated the influence of the marrow microenvironment on bone vascular function in young and old rats. An inflamed marrow microenvironment may reduce vasodilator capacity of bone blood vessels, diminishing delivery of blood flow to the skeleton. In young rats, the presence of the marrow reduced vasodilation in the femoral principal nutrient artery (PNA). However, intermittent parathyroid hormone administration (i.e., a treatment for osteoporosis) improved the marrow microenvironment and vasodilator capacity in old PNAs.

Aging induces muscle-specific impairment of endothelium-dependent dilation in skeletal muscle feed arteries

2002 ◽  
Vol 93 (5) ◽  
pp. 1685-1690 ◽  
Author(s):  
Christopher R. Woodman ◽  
Elmer M. Price ◽  
M. Harold Laughlin
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Vascular Function ◽  
Fischer 344 ◽  
Old Rats ◽  
The Right ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Feed Arteries ◽  
Skeletal Muscle Feed Arteries

We tested the hypothesis that aging decreases endothelium-dependent vasodilation in feed arteries perfusing rat skeletal muscle. In addition, we tested the hypothesis that attenuated vasodilator responses are associated with decreased endothelial nitric oxide synthase (eNOS) and superoxide dismutase-1 (SOD-1) expression. Soleus feed arteries (SFA) and gastrocnemius feed arteries (GFA) were isolated from young (4 mo) and old (24 mo) male Fischer 344 rats. Feed arteries from the right hindlimb were cannulated with two glass micropipettes for examination of endothelium-dependent [acetylcholine (ACh)] and endothelium-independent [adenosine (Ado) or sodium nitroprusside (SNP)] vasodilator function. Feed arteries from the left hindlimb were frozen and used to assess eNOS and SOD-1 protein and mRNA expression. In SFA, endothelium-dependent dilation to ACh was reduced in old rats (0.9 ± 0.04 vs. 0.8 ± 0.03), whereas dilator responses to Ado and SNP were similar in SFA of young and old rats. In GFA, vasodilator responses to ACh, Ado, and SNP were not altered by age. eNOS and SOD-1 protein expression declined with age in SFA (−71 and −54%, respectively) but not in GFA. eNOS and SOD-1 mRNA expression were not altered by age in SFA or GFA. Collectively, these data indicate aging induces muscle-specific impairment of endothelium-dependent vascular function in SFA.

scholarly journals Intermittent parathyroid hormone administration attenuates endothelial dysfunction in old rats

2017 ◽  
Vol 122 (1) ◽  
pp. 76-81 ◽  
Author(s):  
John J. Guers ◽  
Rhonda D. Prisby ◽  
David G. Edwards ◽  
Shannon Lennon-Edwards
Keyword(s):  
Parathyroid Hormone ◽  
Endothelial Function ◽  
Vascular Dysfunction ◽  
Area Under The Curve ◽  
Enos Expression ◽  
Fischer 344 ◽  
Hormone Administration ◽  
Age Related ◽  
Intermittent Pth ◽  
Aortic Endothelial

Aging is an independent risk factor for cardiovascular disease and is characterized by a decline in endothelial function. Parathyroid hormone (PTH) administration has been shown to increase endothelial nitric oxide synthase (eNOS) expression. The purpose of this investigation was to determine the effect of intermittent PTH administration on aortic endothelial function in old rodents. We hypothesized that intermittent PTH administration would improve endothelial function in older rodents. Old (24-mo-old) and young (4-mo-old) Fischer-344 rats were given 10 injections of PTH 1–34 (43 μg·kg−1·day−1) or phosphate-buffered saline (100 μl/day) over 15 days. Endothelium-dependent relaxation of aortic rings in response to acetylcholine (10−9 to 10−5 M) was significantly impaired in old control (OC) compared with young control (YC) as indicated by a reduced area under the curve (AUC, 100 ± 6.28 vs. 54.08 ± 8.3%; P < 0.05) and impaired maximal relaxation (Emax, 70.1 ± 4.48 vs. 92.9 ± 4.38%; P < 0.05). Emax was improved in old animals treated with PTH (OPTH) (OC, 70.1 ± 4.48 vs. OPTH, 85 ± 7.48%; P < 0.05) as well as AUC (OC, 54.08 ± 8.3 vs. OPTH, 82.5 ± 5.7%; P < 0.05) while logEC50 was not different. Endothelial-independent relaxation in response to sodium nitroprusside was not different among groups. Aortic eNOS protein expression was significantly decreased in OC compared with YC ( P < 0.05). PTH treatment restored eNOS expression in OPTH animals ( P < 0.05). These data suggest that PTH may play a role in attenuating age-related impairments in aortic endothelial function. NEW & NOTEWORTHY We have demonstrated that intermittent parathyroid hormone administration can rescue age-related vascular dysfunction by improving endothelial-dependent dilation in the aorta of older rodents. This demonstrates a novel potential benefit of parathyroid hormone administration in aging.

Exercise training enhances flow-induced vasodilation in skeletal muscle resistance arteries of aged rats: role of PGI2 and nitric oxide

2007 ◽  
Vol 292 (6) ◽  
pp. H3119-H3127 ◽  
Author(s):  
Scott A. Spier ◽  
Michael D. Delp ◽  
John N. Stallone ◽  
James M. Dominguez ◽  
Judy M. Muller-Delp
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Gastrocnemius Muscle ◽  
Aged Rats ◽  
Resistance Arteries ◽  
Fischer 344 ◽  
Young Rats ◽  
Old Rats ◽  
Gastrocnemius Muscles

Flow-induced vasodilation is attenuated with old age in rat skeletal muscle arterioles. The purpose of this study was to determine whether diminished cyclooxygenase (COX) signaling contributes to the age-induced attenuation of flow-induced vasodilation in gastrocnemius muscle arterioles and to determine whether, and through which mechanism(s), exercise training restores this deficit in old rats. Fischer 344 rats (3 and 22 mo old) were assigned to a sedentary or exercise-trained group. First-order arterioles were isolated from the gastrocnemius muscles, cannulated, and pressurized to 70 cmH2O. Diameter changes were determined in response to graded increases in intraluminal flow in the presence and absence of nitric oxide synthase (NOS) inhibition [10−5 M NG-nitro-l-arginine methyl ester (l-NAME)], COX inhibition (10−5 M indomethacin), or combination NOS (10−5 Ml-NAME) plus COX (10−5 M indomethacin) inhibition. Aging reduced flow-induced vasodilation in gastrocnemius muscle arterioles. Exercise training restored responsiveness to flow in arterioles of aged rats and enhanced flow-induced vasodilation in arterioles from young rats. l-NAME inhibition of flow-induced vasodilation was greater in arterioles from old rats compared with those from young rats and was increased after exercise training in arterioles from both young and old rats. Although the indomethacin-sensitive portion of flow-induced dilation was not altered by age or training, both COX-1 mRNA expression and PGI2 production increased with training in arterioles from old rats. These data demonstrate that exercise training restores flow-induced vasodilation in gastrocnemius muscle arterioles from old rats and enhances flow-induced vasodilation in gastrocnemius muscle arterioles from young rats. In arterioles from both old and young rats, the exercise training-induced enhancement of flow-induced dilation occurs primarily through a NOS mechanism.

Gene transfer of extracellular superoxide dismutase protects against vascular dysfunction with aging

2006 ◽  
Vol 290 (6) ◽  
pp. H2600-H2605 ◽  
Author(s):  
Kathryn A. Brown ◽  
Yi Chu ◽  
Donald D. Lund ◽  
Donald D. Heistad ◽  
Frank M. Faraci
Keyword(s):  
Superoxide Dismutase ◽  
Gene Transfer ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Extracellular Superoxide Dismutase ◽  
Heparin Binding ◽  
Aged Rats ◽  
Young Rats ◽  
Heparin Binding Domain ◽  
Old Rats

Aging is an independent risk factor for cardiovascular disease, but mechanisms leading to vascular dysfunction have not been fully elucidated. Recent studies suggest that oxidative stress may increase in blood vessels during aging. Levels of superoxide are influenced by the activity of SODs. The goal of this study was to examine the effect of extracellular superoxide dismutase (ECSOD) on superoxide levels and vascular function in an animal model of aging. Aortas from young (4–8 mo old) and old (29–31 mo old) Fischer 344 rats were examined in vitro. Relaxation of aorta to ACh was impaired in old rats compared with young rats; e.g., 3 μM ACh produced 57 ± 4% (mean ± SE) and 84 ± 2% relaxation in old and young rats, respectively ( P < 0.0001). Three days after gene transfer of adenovirus expressing human ECSOD (AdECSOD), the response to ACh was not affected in young rats but was improved in old rats. There was no difference in relaxation to the endothelium-independent dilator sodium nitroprusside between young, aged, and AdECSOD-treated old rats. Superoxide levels (lucigenin-enhanced chemiluminescence) were significantly increased in aged rats compared with young rats. After gene transfer of ECSOD to aged rats, superoxide levels in aorta were similar in old and young rats. Gene transfer of an ECSOD with the heparin-binding domain deleted had no effect on vascular function or superoxide levels in old rats. These results suggest that 1) vascular dysfunction associated with aging is mediated in part by increased levels of superoxide, 2) gene transfer of ECSOD reduces vascular superoxide and dysfunction in old rats, and 3) beneficial effects of ECSOD in old rats require the heparin-binding domain of ECSOD.

scholarly journals NAD(P)H oxidase-derived reactive oxygen species contribute to age-related impairments of endothelium-dependent dilation in rat soleus feed arteries

2011 ◽  
Vol 110 (5) ◽  
pp. 1171-1180 ◽  
Author(s):  
Daniel W. Trott ◽  
John W. Seawright ◽  
Meredith J. Luttrell ◽  
Christopher R. Woodman
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Immunoblot Analysis ◽  
Oxidase Inhibitor ◽  
Oxygen Species ◽  
Fischer 344 ◽  
Young Rats ◽  
Age Related ◽  
Old Rats ◽  
Feed Arteries

We tested the hypothesis that age-related endothelial dysfunction in rat soleus muscle feed arteries (SFA) is mediated in part by NAD(P)H oxidase-derived reactive oxygen species (ROS). SFA from young (4 mo) and old (24 mo) Fischer 344 rats were isolated and cannulated for examination of vasodilator responses to flow and acetylcholine (ACh) in the absence or presence of a superoxide anion (O2−) scavenger (Tempol; 100 μM) or an NAD(P)H oxidase inhibitor (apocynin; 100 μM). In the absence of inhibitors, flow- and ACh-induced dilations were attenuated in SFA from old rats compared with young rats. Tempol and apocynin improved flow- and ACh-induced dilation in SFA from old rats. In SFA from young rats, Tempol and apocynin had no effect on flow-induced dilation, and apocynin attenuated ACh-induced dilation. To determine the role of hydrogen peroxide (H2O2), dilator responses were assessed in the absence and presence of catalase (100 U/ml) or PEG-catalase (200 U/ml). Neither H2O2 scavenger altered flow-induced dilation, whereas both H2O2 scavengers blunted ACh-induced dilation in SFA from young rats. In old SFA, catalase improved flow-induced dilation whereas PEG-catalase improved ACh-induced dilation. Compared with young SFA, in response to exogenous H2O2 and NADPH, old rats exhibited blunted dilation and constriction, respectively. Immunoblot analysis revealed that the NAD(P)H oxidase subunit gp91phox protein content was greater in old SFA compared with young. These results suggest that NAD(P)H oxidase-derived reactive oxygen species contribute to impaired endothelium-dependent dilation in old SFA.

scholarly journals Exercise training reverses aging-induced impairment of myogenic constriction in skeletal muscle arterioles

2015 ◽  
Vol 118 (7) ◽  
pp. 904-911 ◽  
Author(s):  
Payal Ghosh ◽  
Fredy R. Mora Solis ◽  
James M. Dominguez ◽  
Scott A. Spier ◽  
Anthony J. Donato ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Channel Blocker ◽  
Fischer 344 Rats ◽  
Channel Blockade ◽  
Fischer 344 ◽  
Young Rats ◽  
Age Related ◽  
Old Rats ◽  
And Training

To investigate whether exercise training can reverse age-related impairment of myogenic vasoconstriction in skeletal muscle arterioles, young (4 mo) and old (22 mo) male Fischer 344 rats were randomly assigned to either sedentary or exercise-trained groups. The roles of the endothelium and Kv1 channels in age- and exercise training-induced adaptations of myogenic responses were assessed through evaluation of pressure-induced constriction in endothelium-intact and denuded soleus muscle arterioles in the presence and absence of the Kv1 channel blocker, correolide. Exercise training enhanced myogenic constriction in arterioles from both old and young rats. In arterioles from old rats, exercise training restored myogenic constriction to a level similar to that of arterioles from young sedentary rats. Removal of the endothelium did not alter myogenic constriction of arterioles from young sedentary rats, but reduced myogenic constriction in arterioles from young exercise-trained rats. In contrast, endothelial removal had no effect on myogenic constriction of arterioles from old exercise-trained rats, but increased myogenic vasoconstriction in old sedentary rats. The effect of Kv1 channel blockade was also dependent on age and training status. In arterioles from young sedentary rats, Kv1 blockade had little effect on myogenic constriction, whereas in old sedentary rats Kv1 blockade increased myogenic constriction. After exercise training, Kv1 channel blockade increased myogenic constriction in arterioles from both young and old rats. Thus exercise training restores myogenic constriction of arterioles from old rats and enhances myogenic constriction from young rats through adaptations of the endothelium and smooth muscle Kv1 channels.

Tempol improves vascular function in the mesenteric vascular bed of senescent rats

2004 ◽  
Vol 82 (3) ◽  
pp. 200-207 ◽  
Author(s):  
R Tatchum-Talom ◽  
D S Martin
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Vascular Function ◽  
Chronic Treatment ◽  
Young Rats ◽  
Arterial Blood ◽  
Vascular Bed ◽  
Old Rats ◽  
Mesenteric Vascular Bed

Ageing is associated with structural and functional alterations of the vasculature. The nature of age-related vascular disorders is not completely understood. Oxidative stress is hypothesized to play a crucial role in the pathophysiology of vascular complications. We investigated the effects of chronic treatment with the superoxide dismutase mimetic tempol (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl) on vascular function in the mesenteric vasculature of aged rats. Young (3 weeks) and old (40 weeks) Sprague–Dawley rats were treated with tempol (1 mM in drinking water) or vehicle for 3 weeks. Arterial blood pressure was slightly, but significantly, higher in old than in young rats. Tempol had no effect on arterial blood pressure. The vasoconstrictor responses to norepinephrine (NE) and serotonin (5-HT) were exaggerated in the mesenteric vascular bed (MVB) removed from old rats. Vasodilator responses to acetylcholine (ACh), papaverine (PPV), and isoprenaline (ISO) were reduced in the MVB of old rats in comparison with young rats. Chronic treatment of old rats with tempol normalized their responses to NE and 5-HT. The dilator responses to ACh, PPV, and ISO were similar between old rats receiving tempol and young rats. The present findings suggest that oxidative stress contributes to vascular dysfunction in the mesentery of old rats. The vasculoprotective effects of tempol remain to be elucidated.Key words: ageing, oxidative stress, vascular reactivity.

Autoradiography of Incorporated Leucine-H3 in the Enamel Matrix and Enamel Organ of the Upper Incisor of the Rat

1964 ◽  
Vol 04 (02) ◽  
pp. 186-192
Author(s):  
Leonel Costacurta
Keyword(s):  
Amino Acid ◽  
Blood Vessels ◽  
Tooth Germ ◽  
Longitudinal Section ◽  
Equal Length ◽  
Enamel Organ ◽  
Enamel Matrix ◽  
Distal Extremity ◽  
Old Rats ◽  
Thin Band

SummaryDental germs of the upper incisors of six-days old rats were studied for the uptake of leucine-H3 by different layers of the enamel organ in correlation to the various stages of the development of enamel.The longitudinal section of the tooth germ was divided into 15 zones of about equal length in order to facilitate the description and interpretation of results. Autoradiographic images of the histologic preparations from rats sacrificed 30 minutes, 1 hour, 1 day and 3 days after the injection were made. The strongest reactions were observed in dental germs of rats sacrificed 1 hour, and particularly one day, after the leucine-H3 injection.The uptake of this compound by the enamel matrix increases progressively up to the young enamel and then decreases to the distal extremity; the greatest quantity of this labeled amino-acid was observed in the primary and young enamel. The reactions were present in the transitional enamel only along a thin band close to the dentine-enamel junction.In the enamel organ leucine-H3 incorporation was greatest in the three layers, the zones corresponding to primary and young enamel. In zones corresponding to transitional enamel, the inner epithelium showed a small quantity, and the stellate reticulum a blackening only in its superficial part, were the blood vessels reach the enamel organ.

scholarly journals Influence of Intermittent Parathyroid Hormone (PTH) Administration on the Outcomes of Orthodontic Tooth Movement—A Systematic Review

2021 ◽  
Vol 11 (11) ◽  
pp. 5268
Author(s):  
Zohaib Khurshid ◽  
Faris Yahya Asiri
Keyword(s):  
Parathyroid Hormone ◽  
Animal Studies ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Inclusion Criteria ◽  
Medical Subject Headings ◽  
Periodontal Tissues ◽  
Minimal Bias ◽  
Intermittent Pth

Objective: The aim of this review is to summarize the effects of local and systemic PTH administration on periodontal tissues during orthodontic tooth movement. Materials and methods: An electronic search was conducted on the following databases: PubMed/MEDLINE, Google Scholar, SCOPUS and Embase. On PubMed/MEDLINE, the Medical Subject Headings (MeSH) keywords used were: “orthodontic tooth movement” OR (“tooth” (All Fields) AND “tooth movement” (All Fields)) OR “tooth movement” (All Fields)) AND (“parathyroid hormone”); all studies included using CONSORT. Results: After elimination of duplicates and articles not meeting our inclusion criteria, seven animal studies were included in this review. Although the majority of the studies suggest that PTH may a have a favorable outcome on OTM, most studies were found to have several sources of bias. Conclusion: Animal studies with minimal bias and long-term clinical studies are needed to ascertain the efficacy of intermittent PTH administration in improving the rate and retention of OTM.

Cold-induced thermogenesis in younger and older Fischer 344 rats following exercise training

1988 ◽  
Vol 254 (6) ◽  
pp. R908-R916 ◽  
Author(s):  
R. B. McDonald ◽  
B. A. Horwitz ◽  
J. S. Stern
Keyword(s):  
Exercise Training ◽  
Body Mass ◽  
Cold Exposure ◽  
O2 Consumption ◽  
Fischer 344 ◽  
Before And After ◽  
Old Rats ◽  
F344 Rats ◽  
Maintain Body Temperature ◽  
Brown Fat Mitochondria

The inability of old rats to maintain body temperature during cold exposure has been well documented. This study evaluated the effect of exercise on the rates of cold-induced O2 consumption and the contribution of nonshivering thermogenesis (NST) to these rates. Younger (12 mo) and older (24 mo) male Fischer 344 (F344) rats were divided into exercised and sedentary groups. Exercised rats were run on a motor-driven treadmill 60 min/day, at 19-24 m/min, 5 days/wk for 6 mo. At the conclusion of the 6-mo training period, O2 consumption of all four groups was measured at thermoneutrality (26 degrees C) and during 6 h of exposure to 6 degrees C. Rectal temperatures were recorded before and after cold exposure. NST was estimated from the ability of isolated brown fat mitochondria to bind guanosine 5'-diphosphate (GDP). Core temperature of older sedentary rats fell 5.1 +/- 0.4 degrees C after cold exposure (36.3 +/- 0.3 vs. 31.2 +/- 0.8 degrees C). Exercise training in older animals prevented this fall from occurring (36.4 +/- 0.2 vs. 35.3 +/- 0.3 degrees C). Core temperatures of cold-exposed younger exercised and sedentary rats did not differ from thermoneutral values. Exercise did not alter the rates of resting body mass-independent (ml.min-1.kg body mass-0.67) O2 consumption in younger or older rats. However, body mass-independent and lean body mass (LBM)-independent (ml.min-1.g LBM-0.67) cold-induced O2 consumptions of older exercised rats were significantly elevated relative to those of older sedentary animals. This effect of exercise was not seen in younger rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Sign in / Sign up

Export Citation Format

Share Document