Hindlimb unweighting decreases ecNOS gene expression and endothelium-dependent dilation in rat soleus feed arteries

1999 ◽  
Vol 87 (4) ◽  
pp. 1476-1482 ◽  
Author(s):  
Jeffrey L. Jasperse ◽  
Christopher R. Woodman ◽  
Elmer M. Price ◽  
Eileen M. Hasser ◽  
M. Harold Laughlin
Keyword(s):  
Blood Flow ◽  
Protein Expression ◽  
Muscle Blood Flow ◽  
Sprague Dawley ◽  
Hindlimb Unweighting ◽  
Sprague Dawley Rats ◽  
Reduced Physical Activity ◽  
Mrna And Protein Expression ◽  
Oxide Synthase ◽  
Feed Arteries

We tested the hypothesis that hindlimb unweighting (HLU) and the associated reduction in soleus muscle blood flow causes decreased expression of endothelial cell nitric oxide synthase (ecNOS) mRNA and protein and attenuated endothelium-dependent vasodilator responses in rat soleus feed arteries (SFA). Male Sprague-Dawley rats were exposed to HLU ( n = 12) or cage control (Con; n = 12) conditions for 14 days. At the end of this period, SFA were isolated, removed, and cannulated with two glass micropipettes for examination of vasodilator responses or frozen for analysis of ecNOS mRNA and protein expression. RT-PCR of RNA from single SFA was used to measure ecNOS mRNA, and immunoblots on single SFAs were used to measure ecNOS protein content. Results revealed that both ecNOS mRNA and ecNOS protein expression were lower in SFA from HLU rats. Dilation to increased intraluminal flow was attenuated in SFA from HLU rats (Con: 88 ± 8% vs. HLU: 53 ± 8%) as was maximal vasodilation to acetylcholine (10−9-10−4M; Con: 88 ± 5% vs. HLU: 73 ± 5%). Sensitivity to the endothelium-independent vasodilator sodium nitroprusside (10−10-10−4M) was enhanced by HLU (EC50: Con: 4.46 × 10−7 M vs. HLU: 5.00 × 10−8 M). Collectively, these data indicate that the chronic reduction in soleus blood flow associated with the reduced physical activity during HLU results in reduced expression of ecNOS mRNA and protein in SFA and attenuated endothelium-dependent vasodilation.

Mechanisms of flow and ACh-induced dilation in rat soleus arterioles are altered by hindlimb unweighting

2002 ◽  
Vol 92 (3) ◽  
pp. 901-911 ◽  
Author(s):  
William G. Schrage ◽  
Christopher R. Woodman ◽  
M. Harold Laughlin
Keyword(s):  
Weight Bearing ◽  
Combined Treatment ◽  
Sprague Dawley ◽  
Hindlimb Unweighting ◽  
First Order ◽  
Sprague Dawley Rats ◽  
Independent Mechanism ◽  
Rat Soleus Muscle ◽  
Luminal Flow ◽  
Oxide Synthase

The purpose of this study was to test the hypothesis that endothelium-dependent dilation (flow-induced dilation and ACh-induced dilation) in rat soleus muscle arterioles is impaired by hindlimb unweighting (HLU). Male Sprague-Dawley rats (∼300 g) were exposed to HLU or weight-bearing control (Con) conditions for 14 days. Soleus first-order (1A) and second-order (2A) arterioles were isolated, cannulated, and exposed to step increases in luminal flow at constant pressure. Flow-induced dilation was not impaired by HLU in 1A or 2A arterioles. The cyclooxygenase inhibitor indomethacin (Indo; 50 μM) did not alter flow-induced dilation in 1As or 2As. Inhibition of nitric oxide synthase (NOS) with N ω-nitro-l-arginine (l-NNA; 300 μM) reduced flow-induced dilation by 65–70% in Con and HLU 1As. In contrast, l-NNA abolished flow-induced dilation in 2As from Con rats but had no effect in HLU 2As. Combined treatment with l-NNA + Indo reduced tone in 1As and 2As from Con rats, but flow-induced dilation in the presence of l-NNA + Indo was not different from responses without inhibitors in either Con or HLU 1As or 2As. HLU also did not impair ACh-induced dilation (10−9-10−4 M) in soleus 2As.l-NNA reduced ACh-induced dilation by ∼40% in Con 2As but abolished dilation in HLU 2As. Indo did not alter ACh-induced dilation in Con or HLU 2As, whereas combined treatment withl-NNA + Indo abolished ACh-induced dilation in 2As from both groups. We conclude that flow-induced dilation (1As and 2As) was preserved after 2 wk HLU, but HLU decreased the contribution of NOS in mediating flow-induced dilation and increased the contribution of a NOS- and cyclooxygenase-independent mechanism (possibly endothelium-derived hyperpolarizing factor). In soleus 2As, ACh-induced dilation was preserved after 2-wk HLU but the contribution of NOS in mediating ACh-induced dilation was increased.

scholarly journals Hindlimb unweighting decreases endothelium-dependent dilation and eNOS expression in soleus not gastrocnemius

2001 ◽  
Vol 91 (3) ◽  
pp. 1091-1098 ◽  
Author(s):  
Christopher R. Woodman ◽  
William G. Schrage ◽  
James W. E. Rush ◽  
Chester A. Ray ◽  
Elmer M. Price ◽  
...  
Keyword(s):  
Blood Flow ◽  
Protein Content ◽  
Sprague Dawley ◽  
Enos Expression ◽  
Hindlimb Unweighting ◽  
Sprague Dawley Rats ◽  
Mrna Content ◽  
Enos Mrna ◽  
Endothelial Nitric Oxide

We tested the hypothesis that hindlimb unweighting (HLU) decreases endothelium-dependent vasodilation and expression of endothelial nitric oxide synthase (eNOS) and superoxide dismutase-1 (SOD-1) in arteries of skeletal muscle with reduced blood flow during HLU. Sprague-Dawley rats (300–350 g) were exposed to HLU ( n = 15) or control ( n = 15) conditions for 14 days. ACh-induced dilation was assessed in muscle with reduced [soleus (Sol)] or unchanged [gastrocnemius (Gast)] blood flow during HLU. eNOS and SOD-1 expression were measured in feed arteries (FA) and in first-order (1A), second-order (2A), and third-order (3A) arterioles. Dilation to infusion of ACh in vivo was blunted in Sol but not Gast. In arteries of Sol muscle, HLU decreased eNOS mRNA and protein content. eNOS mRNA content was significantly less in Sol FA (35%), 1A arterioles (25%) and 2A arterioles (18%). eNOS protein content was less in Sol FA (64%) and 1A arterioles (65%) from HLU rats. In arteries of Gast, HLU did not decrease eNOS mRNA or protein. SOD-1 mRNA expression was less in Sol 2A arterioles (31%) and 3A arterioles (29%) of HLU rats. SOD-1 protein content was less in Sol FA (67%) but not arterioles. SOD-1 mRNA and protein content were not decreased in arteries from Gast. These data indicate that HLU decreases endothelium-dependent vasodilation, eNOS expression, and SOD-1 expression primarily in arteries of Sol muscle where blood flow is reduced during HLU.

scholarly journals P0761STUDY ON THE MECHANISM OF MICROINFLAMMATION WITH UREMIA CAUSED BY LACTOBACILLUS ACTIVATION OF INTESTINAL MACROPHAGES BY MINCLE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Lingshuang Sun
Keyword(s):  
Protein Expression ◽  
Sham Group ◽  
Intestinal Bacteria ◽  
Diabetic Patients ◽  
Sprague Dawley ◽  
Transmission Electron ◽  
Sprague Dawley Rats ◽  
Mrna And Protein Expression ◽  
End Stage ◽  
The Relationship

Abstract Background and Aims My previous studies have found that Intestinal macrophages in the uremic rats are polarized towards a proinflammatory phenotype and had dysfunction of phagocytosis leading to aggravate microinflammation and assist bacterial translocation in uremia resulting in microinflammation. However, it is still unclear what kind of mechanism of action of intestinal bacteria activates intestinal macrophages and thus participates in the occurrence and development of microinflammation in uremia. Method Male Sprague-Dawley rats were randomly divided into two groups: sham, uremia. The macrophage ultrastructure was examined by transmission electron microscopy. Immunochemistry was used to analyze the expression of macrophage-inducible C-type lectin (Mincle). RT-PCR and western blot were employed to assess the mRNA and protein expression of toll-like receptor 4 (TLR4). Results Our RCT study found that the number of Lactobacilli in the intestines of patients with end-stage diabetic nephropathy was significantly higher than that in non-diabetic patients(Figure 1). The plasma levels of endotoxin, CRP, IL-6, and TNF-a in the uremia group were greater than those in the sham group (p>0.05)(Table 1).Compared with the sham group, the uremic macrophages showed fewer cytoplasmic protrusions and pseudopodia(Figure 2) and the uremia group exhibited macrophages with higher staining intensities for Mincle and higher mRNA and protein expression of TLR4(Figure 3-5). Conclusion Studies have shown that Lactobacillus planta can directly activate Mincle. The relationship between Mincle and the activation of intestinal macrophages was verified. The solution to this scientific problem will not only clarify the molecular mechanism of intestinal bacteria in controlling the activation of intestinal macrophages, but also link the immune regulation of intestinal macrophages with the micro-inflammation of uremia so as to clarify the micro-inflammation state of uremia.

Oxygen consumption and distribution of blood flow in rats climbing a laddermill

1990 ◽  
Vol 68 (1) ◽  
pp. 241-247 ◽  
Author(s):  
K. I. Norton ◽  
M. T. Jones ◽  
R. B. Armstrong
Keyword(s):  
Blood Flow ◽  
Fiber Type ◽  
Muscle Blood Flow ◽  
Flow Distribution ◽  
Treadmill Running ◽  
Blood Flow Distribution ◽  
Sprague Dawley ◽  
Circulatory Response ◽  
Blood Flows ◽  
Sprague Dawley Rats

The purpose of this study was threefold: 1) to determine whether untrained rats that refused to run on treadmill would climb on a laddermill (75 degrees incline); 2) to determine O2 consumption (VO2) in untrained rats as a function of laddermill climbing speed; and 3) to determine whether the circulatory response of untrained rats to laddermill climbing is similar to that previously reported for treadmill running at an equivalent VO2. Eighteen female Sprague-Dawley rats that would not perform on a treadmill as part of another study were used to measure VO2 as a function of laddermill speed (5-17 m/min). Data were obtained from all 18 rats; VO2 increased linearly as a function of laddermill speed (r = 0.83, y = 3.0 x + 63.2). Twenty-four female Sprague-Dawley rats that also refused to run on a treadmill were used to measure mean arterial pressure, heart rate, and blood flow distribution (with microspheres) during climbing at 5 and 10 m/min. These exercise intensities were metabolically equivalent to level treadmill running at 45 and 60 m/min (VO2 approximately 78 and 93 ml.min-1.kg-1, respectively). Of the 24 animals, 23 were willing to climb. Mean arterial pressures were higher (approximately 10%) during laddermill climbing than during equivalent treadmill running, but heart rates were the same. General blood flow distribution among muscles as a function of fiber type (with red muscles receiving higher flows) and between muscles and visceral tissues (muscle blood flow increased as a function of exercise intensity while visceral blood flows decreased) were similar to data for rats running on the level.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effects of maternal enflurane exposure on NR2B expression in the hippocampus of their offspring

2015 ◽  
Vol 51 (3) ◽  
pp. 673-679
Author(s):  
Fo-Quan Luo ◽  
Jun-Wu Liu ◽  
Shu-Xin Tang ◽  
Wei-Lu Zhao ◽  
Yan Hu ◽  
...  
Keyword(s):  
Protein Expression ◽  
Learning And Memory ◽  
Memory Function ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Group 4 ◽  
Sprague Dawley Rats ◽  
Enflurane Anesthesia ◽  
Mrna And Protein Expression ◽  
Spatial Exploration

This work aims to study the pathogenesis of learning and memory impairment in offspring rats resulting from maternal enflurane anesthesia by focusing on the expression of the N-methyl-d-aspartic acid receptor subunit 2B (NR2B) in the hippocampus of the offspring. Thirty female Sprague-Dawley rats were randomly divided into three groups: control (C group), 4 h enflurane exposure (E1 group), and 8 h enflurane exposure (E2 group) groups. Eight to ten days after the initiation of pregnancy, rats from the E1 and E2 groups were allowed to inhale 1.7% enflurane in 2 L/min oxygen for 4 h and 8 h, respectively. Rats from the C group were allowed to inhale 2 L/min of oxygen only. The Morris water maze was used to assay the learning and memory function of the offspring on postnatal days 20 and 30. RT-PCR and immunohistochemistry assays were then used to measure the mRNA levels and protein expression of NR2B, respectively. Relative to offspring rats from the C group, those from the E1 and E2 groups exhibited longer escape latencies, lesser number of crossings over the platform, and less time spent in the target quadrant in the spatial exploration test (P < 0.05). In addition, the mRNA and protein expression levels of NR2B in the hippocampus of offspring rats in the E1 and E2 groups were down-regulated (P < 0.05). No significant differences between the E1 and E2 groups were observed (P > 0.05) in terms of mRNA levels and protein expression of NR2B. The cognitive function of the offspring is impaired when maternal rats are exposed to enflurane during early pregnancy. A possible mechanism of this effect is related to the down-regulation of NR2B expression.

Angiotensin-converting enzyme inhibition increases collateral-dependent muscle blood flow

1993 ◽  
Vol 75 (1) ◽  
pp. 452-457 ◽  
Author(s):  
H. T. Yang ◽  
R. L. Terjung
Keyword(s):  
Blood Flow ◽  
Angiotensin Converting Enzyme ◽  
Muscle Blood Flow ◽  
Ace Inhibition ◽  
Angiotensin Converting Enzyme Inhibition ◽  
High Dose ◽  
Converting Enzyme ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Converting Enzyme Inhibition

The purpose of this study was to evaluate the effect of angiotensin-converting enzyme (ACE) inhibition on collateral-dependent blood flow (BF) during exercise. Adult male Sprague-Dawley rats (approximately 320 g) were fed zabicipril, an ACE inhibitor, mixed with powdered food at 0.0, 0.3, and 3.0 mg.kg-1 x day-1 (n = 12/group) for 5–7 days. Under ketamine-acepromazine anesthesia, the carotid and caudal arteries were catheterized for BF determination, and both femoral arteries were ligated to remove the primary route for BF to the distal limb tissue. Later on the same day, collateral-dependent hindlimb BF was determined at two treadmill speeds (15 and 25 m/min at 15% grade) with 85Sr- and 141Ce-labeled 15-microns microspheres. Zabicipril ingestion induced 50 and 65% inhibition of plasma ACE activity in the low- and high-dose group, respectively (P < 0.001). ACE inhibition did not affect body weight, blood pressure, or heart rate of the rats during exercise. However, BFs to the total hindlimb were 44 and 36% higher (P < 0.001) in zabicipril-treated animals than in the zero-dose controls (approximately 45 ml.min-1 x 100 g-1). Furthermore, BFs to the proximal hindlimb, distal hindlimb, and gastrocnemius-plantaris-soleus group were 33–44% greater in drug-treated than in control animals (P < 0.025). Higher speed (25 m/min) failed to further increase muscle BF; therefore peak BFs were likely achieved. These results indicate that collateral-dependent BF was improved by ACE inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Muscular blood flow distribution patterns as a function of running speed in rats

1982 ◽  
Vol 243 (2) ◽  
pp. H296-H306 ◽  
Author(s):  
M. H. Laughlin ◽  
R. B. Armstrong
Keyword(s):  
Blood Flow ◽  
Muscle Blood Flow ◽  
Flow Distribution ◽  
Distribution Patterns ◽  
Left Renal Artery ◽  
Sprague Dawley ◽  
Vastus Intermedius ◽  
Slow Twitch ◽  
The Right ◽  
White Gastrocnemius

Muscle blood flow (BF) was measured using the radiolabeled microsphere technique within and among nine major muscles of rats before exercise and during treadmill walking or running at speeds of 15, 30, 45, 60, and 75 m/min. Measurements were made during exercise after 1 min of steady walking or running. Male Sprague-Dawley rats were chronically instrumented with 2 Silastic catheters, one in the ascending aorta via the right carotid artery for microsphere infusion and one in the left renal artery for arterial reference blood sample withdrawal. The preexercise results demonstrated that 1) BF to deep slow-twitch muscles was three to four times that to peripheral fast muscles (e.g., soleus and gastrocnemius BFs were 138 and 33 ml . min-1 . 100 g-1, respectively); 2) BFs to red portions within mixed muscles were three to four times those to white portions (e.g, red and white gastrocnemius BFs were 54 and 18 ml . min-1 . 100 g-1, respectively; and 3) there was a direct relationship (P less than 0.05) between BFs to muscles and their slow-twitch oxidative fiber populations. The results obtained during exercise demonstrated that 1) at the slowest speed studied (15 m/min) BFs to the red portions of muscles increased, whereas BFs to the white portions of the same muscles decreased; 2) BFs to all muscles (except soleus) were increased during running at 75 m/min when there was a range of flows of 30 ml . 100 g-1 . min-1 (white gastrocnemius) to 321 (vastus intermedius), 3) at all running speeds the increases in BF to muscles were directly related to the fast-twitch, high-oxidative fiber populations of the muscles; and 4) BFs to visceral tissues and fat were decreased during exercise.

Ammonia reduction with ornithine phenylacetate restores brain eNOS activity via the DDAH-ADMA pathway in bile duct-ligated cirrhotic rats

2012 ◽  
Vol 302 (1) ◽  
pp. G145-G152 ◽  
Author(s):  
Vairappan Balasubramaniyan ◽  
Gavin Wright ◽  
Vikram Sharma ◽  
Nathan A. Davies ◽  
Yalda Sharifi ◽  
...  
Keyword(s):  
Bile Duct ◽  
Protein Expression ◽  
Ammonia Concentration ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Duct Ligation ◽  
Tnf Α ◽  
No Signaling ◽  
Brain Water

Ammonia is central in the pathogenesis of hepatic encephalopathy, which is associated with dysfunction of the nitric oxide (NO) signaling pathway. Ornithine phenylacetate (OP) reduces hyperammonemia and brain water in cirrhotic animals. This study aimed to determine whether endothelial NO synthase activity is altered in the brain of cirrhotic animals, whether this is associated with changes in the endogenous inhibitor, asymmetric-dimethylarginine (ADMA) and its regulating enzyme, dimethylarginine-dimethylaminohydrolase (DDAH-1), and whether these abnormalities are restored by ammonia reduction using OP. Sprague-Dawley rats were studied 4-wk after bile duct ligation (BDL) ( n = 16) or sham operation ( n = 8) and treated with placebo or OP (0.6 g/kg). Arterial ammonia, brain water, TNF-α, plasma, and brain ADMA were measured using standard techniques. NOS activity was measured radiometrically, and protein expression for NOS enzymes, ADMA, DDAH-1, 4-hydroxynonenol (4HNE), and NADPH oxidase (NOX)-1 were measured by Western blotting. BDL significantly increased arterial ammonia ( P < 0.0001), brain water ( P < 0.05), and brain TNF-α ( P < 0.01). These were reduced significantly by OP treatment. The estimated eNOS component of constitutive NOS activity was significantly lower ( P < 0.05) in BDL rat, and this was significantly attenuated in OP-treated animals. Brain ADMA levels were significantly higher and brain DDAH-1 significantly lower in BDL compared with sham ( P < 0.01) and restored toward normal following treatment with OP. Brain 4HNE and NOX-1 protein expression were significantly increased in BDL rat brain, which were significantly decreased following OP administration. We show a marked abnormality of NO regulation in cirrhotic rat brains, which can be restored by reduction in ammonia concentration using OP.

Blood flow in normal and denervated muscle during exercise in conscious rats

1988 ◽  
Vol 255 (6) ◽  
pp. H1509-H1515 ◽  
Author(s):  
M. D. Delp ◽  
R. B. Armstrong
Keyword(s):  
Blood Flow ◽  
Muscular Activity ◽  
Sprague Dawley ◽  
Blood Flows ◽  
Sprague Dawley Rats ◽  
Mechanical Factors ◽  
Denervated Muscles ◽  
Gastrocnemius Muscles ◽  
Low Intensity Exercise ◽  
Hyperemic Response

The purpose of this study was to test the hypothesis that extrinsic mechanical factors, i.e., the dynamic shortening and lengthening imposed on a muscle during limb movements and the rhythmic compressions as surrounding muscles contract and relax, contribute to the initial muscle hyperemia during locomotion in conscious male Sprague-Dawley rats. Soleus and lateral head of gastrocnemius muscles were surgically denervated in one hindlimb several hours before exercise to remove 1) local metabolic vasodilator effects, 2) vasoconstrictor or vasodilatory influences mediated through sympathetic postganglionic fibers, and 3) intrinsic mechanical pumping. Blood flow was measured with radioactive microspheres during preexercise and at 30 s and 5 min of exercise in rats walking at 15 m/min or a motor-driven treadmill. Glycogen concentrations were also measured as an indicator of muscular activity to verify the denervation. Blood flows to control muscles in the normal limb were similar to previously reported values during preexercise and exercise. Denervation, however, decreased preexercise blood flow (69–88%) to muscle composed predominantly of oxidative fibers and increased flow (53%) to muscle composed predominantly of glycolytic fibers. During exercise, blood flow to denervated muscles either remained unchanged or decreased. These data suggest that extrinsic mechanical factors do not significantly contribute to the initial hyperemic response at the onset of low-intensity exercise in normal muscle.

Differential sympathetic nerve responses to nitric oxide synthase inhibition in anesthetized rats

1995 ◽  
Vol 269 (4) ◽  
pp. R807-R813 ◽  
Author(s):  
T. Hirai ◽  
T. I. Musch ◽  
D. A. Morgan ◽  
K. C. Kregel ◽  
D. E. Claassen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sympathetic Nerve ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Important Means ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Tonic Excitation

Recent studies have suggested that the interaction between the sympathetic nervous system and nitric oxide (NO) or nitrosyl factors may be an important means by which arterial blood pressure is regulated. We investigated whether NO synthase (NOS) inhibition modulates basal sympathetic nerve discharge (SND) in baroreceptor-innervated and -denervated, chloralose-anesthetized Sprague-Dawley rats. We recorded mean arterial pressure (MAP), renal SND, and lumbar SND before and after administration of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg iv). Two minutes after L-NAME administration in baroreceptor-innervated rats, MAP increased (+23 +/- 3 mmHg), whereas renal (-45 +/- 6%, n = 7) and lumbar (-35 +/- 2%, n = 6) SND significantly decreased from control levels. These changes persisted for up to 20 min after L-NAME administration. In baroreceptor-denervated rats, L-NAME increased MAP (+40 +/- 6 mmHg) and decreased lumbar SND (n = 7) (-37 +/- 10% from control at 20 min post-L-NAME). In contrast, renal SND progressively increased (+33 +/- 8% at 20 min post-L-NAME) from control after L-NAME administration in baroreceptor-denervated rats (n = 7). These results demonstrate that NOS inhibition can produce nonuniform changes in SND in baroreceptor-denervated rats and suggest that endogenous nitrosyl factors provide tonic excitation to lumbar SND, whereas they provide a tonic restraint to renal SND.

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