scholarly journals Cyclooxygenase inhibition does not impact the pressor response during static or dynamic mechanoreflex activation in healthy decerebrate rats

2019 ◽  
Vol 317 (3) ◽  
pp. R369-R378 ◽  
Author(s):  
Korynne S. Rollins ◽  
Tyler D. Hopkins ◽  
Alec L. Butenas ◽  
Kennedy P. Felice ◽  
Carl J. Ade ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Pressor Response ◽  
Muscle Afferents ◽  
Triceps Surae ◽  
Prostaglandin E ◽  
Muscle Stretch ◽  
Triceps Surae Muscle ◽  
Cox Inhibitor

Passive limb movement and limb muscle stretch in humans and animals are common experimental strategies used to investigate activation of the muscle mechanoreflex independent of contraction-induced metabolite production. Cyclooxygenase (COX) metabolites, however, are produced by skeletal muscle stretch in vitro and have been found to impact various models of mechanoreflex activation. Whether COX metabolites influence the decerebrate rat triceps surae muscle stretch mechanoreflex model remains unknown. We examined the effect of rat triceps surae muscle stretch on the interstitial concentration of the COX metabolite prostaglandin E2 (PGE2). Interstitial PGE2 concentration was increased above baseline values by 4 min of both static (38% increase, P = 0.01) and dynamic (56% increase, P < 0.01) triceps surae muscle stretch ( n = 10). The 4-min protocol was required to collect enough microdialysis fluid for PGE2 detection. The finding that skeletal muscle stretch in vivo was capable of producing COX metabolites prompted the hypothesis that intra-arterial administration of the COX inhibitor indomethacin (1 mg/kg) would reduce the pressor and cardioaccelerator responses evoked during 30 s (the duration most commonly used in the rat mechanoreflex model) of static and dynamic rat triceps surae muscle stretch. We found that indomethacin had no effect ( P > 0.05, n = 9) on the pressor or cardioaccelerator response during 30 s of either static or dynamic stretch. We conclude that, despite the possibility of increased COX metabolite concentration, COX metabolites do not activate or sensitize thin-fiber muscle afferents stimulated during 30 s of static or dynamic hindlimb skeletal muscle stretch in healthy rats.

scholarly journals PPADS does not block contraction-induced prostaglandin E2 synthesis in cat skeletal muscle

2008 ◽  
Vol 295 (5) ◽  
pp. H2043-H2045 ◽  
Author(s):  
Jennifer L. McCord ◽  
Shawn G. Hayes ◽  
Marc P. Kaufman
Keyword(s):  
Skeletal Muscle ◽  
Pyridoxal Phosphate ◽  
Pressor Response ◽  
Triceps Surae ◽  
Prostaglandin E ◽  
Exercise Pressor Reflex ◽  
Before And After ◽  
Pressor Reflex ◽  
Response To Exercise

Pyridoxal-phosphate-6-azophenyl-2′-4-disulfonate (PPADS), a purinergic 2 (P2) receptor antagonist, has been shown to attenuate the exercise pressor reflex in cats. In vitro, however, PPADS has been shown to block the production of prostaglandins, some of which play a role in evoking the exercise pressor reflex. Thus the possibility exists that PPADS blocks the exercise pressor reflex through a reduction in prostaglandin synthesis rather than through the blockade of P2 receptors. Using microdialysis, we collected interstitial fluid from skeletal muscle to determine prostaglandin E2 (PGE2) concentrations during the intermittent contraction of the triceps surae muscle before and after a popliteal arterial injection of PPADS (10 mg/kg). We found that the PGE2 concentration increased in response to the intermittent contraction before and after the injection of PPADS (both, P < 0.05). PPADS reduced the pressor response to exercise ( P < 0.05) but had no effect on the magnitude of PGE2 production during contraction ( P = 0.48). These experiments demonstrate that PPADS does not block the exercise pressor reflex through a reduction in PGE2 synthesis. We suggest that PGE2 and P2 receptors play independent roles in stimulating the exercise pressor reflex.

Reflex cardiovascular responses evoked by selective activation of skeletal muscle ergoreceptors

2001 ◽  
Vol 90 (1) ◽  
pp. 308-316 ◽  
Author(s):  
B. G. Leshnower ◽  
J. T. Potts ◽  
M. G. Garry ◽  
J. H. Mitchell
Keyword(s):  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Cardiovascular Response ◽  
Afferent Fiber ◽  
Cardiovascular Responses ◽  
Muscle Afferents ◽  
Triceps Surae ◽  
Muscle Stretch ◽  
Group Iii ◽  
Passive Muscle

It is well known that the exercise pressor reflex (EPR) is mediated by group III and IV skeletal muscle afferent fibers, which exhibit unique discharge responses to mechanical and chemical stimuli. Based on the difference in discharge patterns of group III and IV muscle afferents, we hypothesized that activation of mechanically sensitive (MS) fibers would evoke a different pattern of cardiovascular responses compared with activation of both MS and chemosensitive (CS) fibers. Experiments were conducted in chloralose-urethane-anesthetized cats ( n = 10). Passive muscle stretch was used to activate MS afferents, and electrically evoked contraction of the triceps surae was used to activate both MS and CS muscle afferents. No significant differences were shown in reflex heart rate and mean arterial pressure (MAP) responses between passive muscle stretch and evoked muscle contraction. However, when the reflex responses were matched according to tension-time index (TTI), the peak MAP response (67 ± 4 vs. 56 ± 4 mmHg, P < 0.05) was significantly greater at higher TTI (427 ± 18 vs. 304 ± 13 kg · s, high vs. low TTI, P < 0.05), despite different modes of afferent fiber activation. When the same mode of afferent fiber activation was compared, the peak MAP response (65 ± 7 vs. 55 ± 5 mmHg, P < 0.05) was again predicted by the magnitude of TTI (422 ± 24 vs. 298 ± 19 kg · s, high vs. low TTI, P < 0.05). Total sensory input from skeletal muscle ergoreceptors, as predicted by TTI and not the modality of afferent fiber activation (muscle contraction vs. passive stretch), is suggested to be the primary determinant of the magnitude of the EPR-evoked cardiovascular response.

Enhanced skeletal muscle arteriolar reactivity to ANG II after recovery from ischemic acute renal failure

2005 ◽  
Vol 289 (6) ◽  
pp. R1770-R1776 ◽  
Author(s):  
David P. Basile ◽  
Deborah L. Donohoe ◽  
Shane A. Phillips ◽  
Jefferson C. Frisbee
Keyword(s):  
Skeletal Muscle ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Pressor Response ◽  
Gracilis Muscle ◽  
Ang Ii ◽  
Sprague Dawley

In addition to the long-term renal complications, previous studies suggested that after acute renal failure (ARF), rats manifest an increased pressor response to an overnight infusion of ANG II. The present study tested whether recovery from ARF results in alterations in sensitivity to the peripheral vasculature. ARF was induced in Sprague-Dawley rats by 45 min of bilateral renal ischemia and reperfusion. Animals were allowed to recover renal structure and function for 5–8 wk, after which the acute pressor responses to ANG II were evaluated either in vivo in in situ skeletal muscle arterioles or in isolated gracilis muscle arteries in vitro. Baseline arterial pressure was not different in ARF rats vs. sham-operated controls, although ARF rats exhibited an enhanced pressor response to bolus ANG II infusion compared with control rats. Steady-state plasma ANG II concentration and plasma renin activity were similar between ARF and control rats. Constrictor reactivity of in situ cremasteric arterioles from ARF rats was enhanced in response to increasing concentrations of ANG II; however, no difference was observed in arteriolar responses to elevated Po2, norepinephrine, acetylcholine, or sodium nitroprusside. Isolated gracilis muscle arteries from ARF rats also showed increased vasoconstriction in response to ANG II but not norepinephrine. In conclusion, recovery from ischemic ARF is not associated with hypertension but is associated with increased arteriolar constrictor reactivity to ANG II. Although the mechanisms of this altered responsiveness are unclear, such changes may relate, in part, to cardiovascular complications in patients with ARF and/or after renal transplant.

NO formation in nucleus tractus solitarii attenuates pressor response evoked by skeletal muscle afferents

2001 ◽  
Vol 280 (5) ◽  
pp. H2371-H2379 ◽  
Author(s):  
Jianhua Li ◽  
Jeffrey T. Potts
Keyword(s):  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Pressor Response ◽  
Extracellular Fluid ◽  
Cardiovascular Responses ◽  
Muscle Afferents ◽  
Nucleus Tractus Solitarii ◽  
Triceps Surae ◽  
No Formation ◽  
Fos Protein

We have previously shown that static muscle contraction induces the expression of c-Fos protein in neurons of the nucleus tractus solitarii (NTS) and that some of these cells were codistributed with neuronal NADPH-diaphorase [nitric oxide (NO) synthase]-positive fibers. In the present study, we sought to determine the role of NO in the NTS in mediating the cardiovascular responses elicited by skeletal muscle afferent fibers. Static contraction of the triceps surae muscle was induced by electrical stimulation of the L7 and S1 ventral roots in anesthetized cats. Muscle contraction during microdialysis of artificial extracellular fluid increased mean arterial pressure (MAP) and heart rate (HR) 51 ± 9 mmHg and 18 ± 3 beats/min, respectively. Microdialysis ofl-arginine (10 mM) into the NTS to locally increase NO formation attenuated the increases in MAP (30 ± 7 mmHg, P < 0.05) and HR (14 ± 2 beats/min, P > 0.05) during contraction. Microdialysis ofd-arginine (10 mM) did not alter the cardiovascular responses evoked by muscle contraction. Microdialysis of N G-nitro-l-arginine methyl ester (2 mM) during contraction attenuated the effects ofl-arginine on the reflex cardiovascular responses. These findings demonstrate that an increase in NO formation in the NTS attenuates the pressor response to static muscle contraction, indicating that the NO system plays a role in mediating the cardiovascular responses to static muscle contraction in the NTS.

scholarly journals Aspirin as a COX inhibitor and anti-inflammatory drug in human skeletal muscle

2017 ◽  
Vol 123 (6) ◽  
pp. 1610-1616 ◽  
Author(s):  
Stephen M. Ratchford ◽  
Kaleen M. Lavin ◽  
Ryan K. Perkins ◽  
Bozena Jemiolo ◽  
Scott W. Trappe ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Time Course ◽  
Human Skeletal Muscle ◽  
Ex Vivo ◽  
Standard Dose ◽  
Prostaglandin E ◽  
Cox Inhibitor ◽  
Muscle Health ◽  
Anti Inflammatory

Although aspirin is one of the most common anti-inflammatory drugs in the world, the effect of aspirin on human skeletal muscle inflammation is almost completely unknown. This study examined the potential effects and related time course of an orally consumed aspirin dose on the inflammatory prostaglandin E2 (PGE2)/cyclooxygenase (COX) pathway in human skeletal muscle. Skeletal muscle biopsies were taken from the vastus lateralis of 10 healthy adults (5 male and 5 female, 25 ± 2 yr old) before (Pre) and 2, 4, and 24 h after (Post) a standard dose (975mg) of aspirin and partitioned for analysis of 1) in vivo PGE2 levels in resting skeletal muscle and 2) ex vivo skeletal muscle PGE2 production when stimulated with the COX substrate arachidonic acid (5 μM). PGE2 levels in vivo and PGE2 production ex vivo were generally unchanged at each time point after aspirin consumption. However, most individuals clearly showed suppression of PGE2, but at varying time points after aspirin consumption. When the maximum suppression after aspirin consumption was examined for each individual, independent of time, PGE2 levels in vivo (184 ± 17 and 104 ± 23pg/g wet wt at Pre and Post, respectively) and PGE2 production ex vivo (2.74 ± 0.17 and 2.09 ± 0.11pg·mg wet wt−1·min−1 at Pre and Post, respectively) were reduced ( P < 0.05) by 44% and 24%, respectively. These results provide evidence that orally consumed aspirin can inhibit the COX pathway and reduce the inflammatory mediator PGE2 in human skeletal muscle. Findings from this study highlight the need to expand our knowledge regarding the potential role for aspirin regulation of the deleterious influence of inflammation on skeletal muscle health in aging and exercising individuals. NEW & NOTEWORTHY This study demonstrated that orally consumed aspirin can target the prostaglandin/cyclooxygenase pathway in human skeletal muscle. This pathway has been shown to regulate skeletal muscle metabolism and inflammation in aging and exercising individuals. Given the prevalence of aspirin consumption, these findings may have implications for skeletal muscle health in a large segment of the population.

scholarly journals Inhibited skeletal muscle healing in cyclooxygenase-2 gene-deficient mice: the role of PGE2 and PGF2α

2006 ◽  
Vol 101 (4) ◽  
pp. 1215-1221 ◽  
Author(s):  
Wei Shen ◽  
Victor Prisk ◽  
Yong Li ◽  
William Foster ◽  
Johnny Huard
Keyword(s):  
Skeletal Muscle ◽  
Healing Process ◽  
Critical Evaluation ◽  
Precursor Cells ◽  
Prostaglandin E ◽  
Muscle Injuries ◽  
Cox 2 ◽  
Myogenic Precursor

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat skeletal muscle injury. However, studies have shown that NSAIDs may be detrimental to the healing process. Mediated by prostaglandin F2α (PGF2α) and prostaglandin E2 (PGE2), the cycloxygenase-2 (COX-2) pathway plays an important role in muscle healing. We hypothesize that the COX-2 pathway is important for the fusion of muscle cells and the regeneration of injured muscle. For the in vitro experiments, we isolated myogenic precursor cells from wild-type (Wt) and COX-2 gene-deficient (COX-2−/−) mice and examined the effect of PGE2 and PGF2α on cell fusion. For the in vivo experiments, we created laceration injury on the tibialis anterior (TA) muscles of Wt and COX-2−/− mice. Five and 14 days after injury, we examined the TA muscles histologically and functionally. We found that the secondary fusion between nascent myotubes and myogenic precursor cells isolated from COX-2−/− mice was severely compromised compared with that of Wt controls but was restored by the addition of PGF2α or, to a lesser extent, PGE2 to the culture. Histological and functional assessments of the TA muscles in COX-2−/− mice revealed decreased regeneration relative to that observed in the Wt mice. The findings reported here demonstrate that the COX-2 pathway plays an important role in muscle healing and that prostaglandins are key mediators of the COX-2 pathway. It suggests that the decision to use NSAIDs to treat muscle injuries warrants critical evaluation because NSAIDs might impair muscle healing by inhibiting the fusion of myogenic precursor cells.

Comparison of in vivo and in vitro prostaglandin E production by squamous cell carcinoma of the head and neck

1994 ◽  
Vol 111 (3) ◽  
pp. 189-196 ◽  
Author(s):  
C SNYDERMAN ◽  
I KLAPAN ◽  
M MILANOVICH ◽  
D HEO ◽  
R WAGNER ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Prostaglandin E

Eph/Ephrin signalling in skeletal muscle development and regeneration

2014 ◽  
Author(s):  
◽  
Danny A. Stark
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Tyrosine Kinases ◽  
Muscle Development ◽  
Receptor Tyrosine Kinases ◽  
Repulsive Interaction ◽  
Type I ◽  
Ephrin Ligands

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Skeletal muscle can be isolated into 642 individual muscles and makes up to one third to one half of the mass of the human body. Each of these muscles is specified and patterned prenatally and after birth they will increase in size and take on characteristics suited to each muscle's unique function. To make the muscles functional, each muscle cell must be innervated by a motor neuron, which will also affect the characteristics of the mature muscle. In a healthy adult, muscles will maintain their specialized pattern and function during physiological homeostasis, and will also recapitulate them if the integrity or health of the muscle is disrupted. This repair and regeneration is dependent satellite cells, the skeletal muscle stem cells. In this dissertation, we study a family of receptor tyrosine kinases, Ephs, and their juxtacrine ephrin ligands in the context of skeletal muscle specification and regeneration. First, using a classical ephrin 'stripe' assay to test for contact-mediated repulsion, we found that satellite cells respond to a subset of ephrins with repulsive motility in vitro and that these forward signals through Ephs also promote patterning of differentiating myotubes parallel to ephrin stripes. This pattering can be replicated in a heterologous in vivo system (the hindbrain of the developing quail, where neural crest cells migrate in streams to the branchial arches, and in the forelimb of the developing quail, where presumptive limb myoblasts emigrate from the somite). Second, we present evidence that specific pairwise interactions between Eph receptor tyrosine kinases and ephrin ligands are required to ensure appropriate muscle innervation when it is originally set during postnatal development and when it is recapitulated after muscle or nerve trauma during adulthood. We show expression of a single ephrin, ephrin-A3, exclusively on type I (slow) myofibers shortly after birth, while its receptor EphA8 is only localized to fast motor endplates, suggesting a functional repulsive interaction for motor axon guidance and/or synaptogenesis. Adult EFNA3-/- mutant mice show a significant loss of slow myofibers, while misexpression of ephrin-A3 on fast myofibers results in a switch from a fast fiber type to slow in the context of sciatic nerve injury and regrowth. Third, we show that EphA7 is expressed on satellite cell derived myocytes in vitro, and marks both myocytes and regenerating myofibers in vivo. In the EPHA7 knockout mouse, we find a regeneration defect in a barium chloride injury model starting 3 days post injection in vivo, and that cultured mutant satellite cells are slow to differentiate and divide. Finally, we present other potential Ephs and ephrins that may affect skeletal muscle, such as EphB1 that is expressed on all MyHC-IIb fibers and a subset of MyHC-IIx fibers, and we show a multitude of Ephs and ephrins at the neuromuscular junction that appear to localize on specific myofibers and at different areas of the synapse. We propose that Eph/ephrin signaling, though well studied in development, continues to be important in regulating post natal development, regeneration, and homeostasis of skeletal muscle.

scholarly journals Effects of aging and exercise training on spinotrapezius muscle microvascular Po2 dynamics and vasomotor control

2011 ◽  
Vol 110 (3) ◽  
pp. 695-704 ◽  
Author(s):  
Danielle J. McCullough ◽  
Robert T. Davis ◽  
James M. Dominguez ◽  
John N. Stabley ◽  
Christian S. Bruells ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Exercise Training ◽  
Sodium Nitroprusside ◽  
Vascular Function ◽  
Treadmill Running ◽  
Aged Rats ◽  
Phosphorescence Quenching

With advancing age, there is a reduction in exercise tolerance, resulting, in part, from a perturbed ability to match O2 delivery to uptake within skeletal muscle. In the spinotrapezius muscle (which is not recruited during incline treadmill running) of aged rats, we tested the hypotheses that exercise training will 1) improve the matching of O2 delivery to O2 uptake, evidenced through improved microvascular Po2 (PmO2), at rest and throughout the contractions transient; and 2) enhance endothelium-dependent vasodilation in first-order arterioles. Young (Y, ∼6 mo) and aged (O, >24 mo) Fischer 344 rats were assigned to control sedentary (YSED; n = 16, and OSED; n = 15) or exercise-trained (YET; n = 14, and OET; n = 13) groups. Spinotrapezius blood flow (via radiolabeled microspheres) was measured at rest and during exercise. Phosphorescence quenching was used to quantify PmO2 in vivo at rest and across the rest-to-twitch contraction (1 Hz, 5 min) transition in the spinotrapezius muscle. In a follow-up study, vasomotor responses to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) stimuli were investigated in vitro. Blood flow to the spinotrapezius did not increase above resting values during exercise in either young or aged groups. Exercise training increased the precontraction baseline PmO2 (OET 37.5 ± 3.9 vs. OSED 24.7 ± 3.6 Torr, P < 0.05); the end-contracting PmO2 and the time-delay before PmO2 fell in the aged group but did not affect these values in the young. Exercise training improved maximal vasodilation in aged rats to acetylcholine (OET 62 ± 16 vs. OSED 27 ± 16%) and to sodium nitroprusside in both young and aged rats. Endurance training of aged rats enhances the PmO2 in a nonrecruited skeletal muscle and is associated with improved vascular smooth muscle function. These data support the notion that improvements in vascular function with exercise training are not isolated to the recruited muscle.

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