scholarly journals The role of the cyclooxygenase products in evoking sympathetic activation in exercise

2007 ◽  
Vol 293 (3) ◽  
pp. H1861-H1868 ◽  
Author(s):  
Jian Cui ◽  
Patrick McQuillan ◽  
Afsana Momen ◽  
Cheryl Blaha ◽  
Raman Moradkhan ◽  
...  
Keyword(s):  
Animal Studies ◽  
Muscle Sympathetic Nerve Activity ◽  
Prostaglandin Synthesis ◽  
Pharmacological Agents ◽  
Exercise Pressor Reflex ◽  
Exercise Blood Pressure ◽  
Before And After ◽  
Pressor Reflex ◽  
Bier Block

Animal studies suggest that prostaglandins in skeletal muscles stimulate afferents and contribute to the exercise pressor reflex. However, human data regarding a role for prostaglandins in this reflex are varied, in part because of systemic effects of pharmacological agents used to block prostaglandin synthesis. We hypothesized that local blockade of prostaglandin synthesis in exercising muscles could attenuate muscle sympathetic nerve activity (MSNA) responses to fatiguing exercise. Blood pressure (Finapres), heart rate, and MSNA (microneurography) were assessed in 12 young healthy subjects during static handgrip and postexercise muscle ischemia (PEMI) before and after local infusion of 6 mg of ketorolac tromethamine in saline via Bier block (regional intravenous anesthesia). In the second experiment ( n = 10), the same amount of saline was infused via the Bier block. Ketorolac Bier block decreased the prostaglandins synthesis to ∼33% of the baseline. After ketorolac Bier block, the increases in MSNA from the baseline during the fatiguing handgrip was significantly lower than that before the Bier block (before ketorolac: Δ502 ± 111; post ketorolac: Δ348 ± 62%, P = 0.016). Moreover, the increase in total MSNA during PEMI after ketorolac was significantly lower than that before the Bier block ( P = 0.014). Saline Bier block had no similar effect. The observations indicate that blockade of prostaglandin synthesis attenuates MSNA responses seen during fatiguing handgrip and suggest that prostaglandins contribute to the exercise pressor reflex.

Role of extracellular Ca2+ in diaphragmatic contraction: effects of ouabain, monensin, and ryanodine

1992 ◽  
Vol 73 (1) ◽  
pp. 30-35 ◽  
Author(s):  
J. H. Zavecz ◽  
W. M. Anderson
Keyword(s):  
Relaxation Time ◽  
Free Solution ◽  
Pharmacological Agents ◽  
Resting Tension ◽  
High K ◽  
Before And After ◽  
Small Muscle ◽  
Ionophore Monensin

The effects of zero extracellular Ca2+ on the contractility of rat diaphragmatic strips in vitro were studied in conjunction with various pharmacological agents known to influence the intracellular Ca2+ concentration: the Na+ ionophore, monensin, and the Na(+)-K+ pump inhibitor, ouabain, which enhance [Ca2+]i, caffeine, which induces Ca2+ release from the sarcoplasmic reticulum (SR), and ryanodine, which prevents Ca2+ retention by the SR. The effect of increasing [Ca2+]i on diaphragmatic contraction was assessed by comparing contractions induced by 120 mM K+ in the small muscle strips before and after the addition of ouabain or monensin. Monensin (20 microM) and ouabain (1–100 microM) augmented contractions up to threefold. Treatment of diaphragm strips with 3 nM ryanodine increased baseline tension 360% above the original resting tension but only if the diaphragm was electrically stimulated concurrently; 100 microM ryanodine induced contracture in quiescent tissue. High K+ contractures were of greater magnitude in the presence of ryanodine compared with control, and relaxation time was prolonged by greater than 200%. Ca(2+)-free conditions ameliorated these actions of ryanodine. Ryanodine reduced contractions induced by 10 mM caffeine and nearly abolished them in Ca(2+)-free solution. The data demonstrate that extracellular Ca2+ is important in certain types of contractile responses of the diaphragm and suggest that the processes necessary to utilize extracellular Ca2+ are present in the diaphragm.

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.

scholarly journals Sympathetic neural recruitment strategies following acute intermittent hypoxia in humans

2020 ◽  
Vol 318 (5) ◽  
pp. R961-R971 ◽  
Author(s):  
Elizabeth P. Ott ◽  
Dain W. Jacob ◽  
Sarah E. Baker ◽  
Walter W. Holbein ◽  
Zachariah M. Scruggs ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Burst Firing ◽  
Neural Firing ◽  
Carotid Chemoreceptors ◽  
Discharge Rates ◽  
Before And After ◽  
Discharge Patterns

We examined the effect of acute intermittent hypoxia (IH) on sympathetic neural firing patterns and the role of the carotid chemoreceptors. We hypothesized exposure to acute IH would increase muscle sympathetic nerve activity (MSNA) via an increase in action potential (AP) discharge rates and within-burst firing. We further hypothesized any change in discharge patterns would be attenuated during acute chemoreceptor deactivation (hyperoxia). MSNA (microneurography) was assessed in 17 healthy adults (11 male/6 female; 31 ± 1 yr) during normoxic rest before and after 30 min of experimental IH. Prior to and following IH, participants were exposed to 2 min of 100% oxygen (hyperoxia). AP patterns were studied from the filtered raw MSNA signal using wavelet-based methodology. Compared with baseline, multiunit MSNA burst incidence ( P < 0.01), AP incidence ( P = 0.01), and AP content per burst ( P = 0.01) were increased following IH. There was an increase in the probability of a particular AP cluster firing once ( P < 0.01) and more than once ( P = 0.03) per burst following IH. There was no effect of hyperoxia on multiunit MSNA at baseline or following IH ( P > 0.05); however, hyperoxia following IH attenuated the probability of particular AP clusters firing more than once per burst ( P < 0.01). Acute IH increases MSNA by increasing AP discharge rates and within-burst firing. A portion of the increase in within-burst firing following IH can be attributed to the carotid chemoreceptors. These data advance the mechanistic understanding of sympathetic activation following acute IH in humans.

scholarly journals Orbitofrontal and Thalamic Influences on Striatal Involvement in Human Reversal Learning

2018 ◽  
Author(s):  
Tiffany Bell ◽  
Angela Langdon ◽  
Michael Lindner ◽  
William Lloyd ◽  
Anastasia Christakou
Keyword(s):  
Reversal Learning ◽  
Animal Studies ◽  
Dorsal Striatum ◽  
Response Strategy ◽  
Cholinergic Interneurons ◽  
Learning Tasks ◽  
Initial Learning ◽  
Before And After ◽  
Psychophysiological Interaction

ABSTRACTCognitive flexibility is crucial for adaptation and is disrupted in neuropsychiatric disorders and psychopathology. Human studies of flexibility using reversal learning tasks typically contrast error trials before and after reversal, which provides little information about the mechanisms that support learning and expressing a new response. However, animal studies suggest a specific role in this latter process for the connections between the dorsal striatum and the centromedian parafascicular (CM-Pf) thalamus, a system which may recruit the striatal cholinergic interneurons, but which is not well understood in humans. This study investigated the role of this system in human probabilistic reversal learning, specifically with respect to learning a new response strategy, contrasting its function to that of the better understood orbitoftontal-striatal systems. Using psychophysiological interaction (PPI) analysis of functional magnetic resonance imaging (fMRI) data we show that connectivity between the striatum and both the lateral orbitofrontal cortex (lOFC) and CM-Pf pathways increased during reversal, but not initial learning. However, while the strength of lOFC-striatal connectivity was associated with the speed of the reversal, the strength of CM-Pf-striatal connectivity was associated specifically with the quality of the reversal (reduced regressive errors). These findings expand our understanding of flexibility mechanisms in the human brain, bridging the gap with animal studies of this system.

The role of acid sensing ion channels in the exercise pressor reflex

2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Shawn G. Hayes ◽  
Angela E. Kindig ◽  
Marc P. Kaufman
Keyword(s):  
Ion Channels ◽  
Exercise Pressor Reflex ◽  
Acid Sensing Ion Channels ◽  
Pressor Reflex

Vasopressin acts in the area postrema to attenuate the exercise pressor reflex in anesthetized cats

1998 ◽  
Vol 274 (6) ◽  
pp. H2116-H2122 ◽  
Author(s):  
Charles L. Stebbins ◽  
Stefani Bonigut ◽  
Lea R. Liviakis ◽  
Paul A. Munch
Keyword(s):  
Blood Pressure ◽  
Area Postrema ◽  
Cardiovascular Response ◽  
Exercise Pressor Reflex ◽  
Arterial Blood ◽  
Baroreflex Function ◽  
Static Contraction ◽  
Before And After ◽  
Pressor Reflex ◽  
Anesthetized Cat

Circulating arginine vasopressin (AVP) can enhance baroreflex function via its action in the area postrema (AP). We tested the hypothesis that AVP acts in the AP to enhance baroreflex function during static contraction and, in turn, attenuates the exercise pressor reflex. Thus mean arterial blood pressure ( n = 9) and heart rate (HR) ( n = 9) during 30 s of electrically stimulated hindlimb contraction were compared before and after bilateral microinjections of 200 nl of the AVP V1-receptor antagonist d(CH2)5Tyr(Me)-AVP (V1x) (1 ng/nl) into the AP of the anesthetized cat. This protocol was repeated in three other cats in which sinoaortic denervation (SAD) was performed before any intervention. Injection of V1xinto the AP had no effect on baseline blood pressure or HR. However, pressor and HR responses to static contraction were augmented by 44 ± 10 and 29 ± 9%, respectively. Static contraction also increased plasma AVP from 15.9 ± 2.0 to 25.5 ± 3.4 pg/ml. In the SAD cats, microinjection of V1x had no effect on contraction-induced increases in blood pressure or HR. These results suggest that baroreflex opposition of the reflex cardiovascular response to static contraction is enhanced by the action of AVP in the AP.

The exercise pressor reflex is attenuated by intrathecal oxytocin

1994 ◽  
Vol 267 (4) ◽  
pp. R909-R915 ◽  
Author(s):  
C. L. Stebbins ◽  
A. Ortiz-Acevedo
Keyword(s):  
Spinal Cord ◽  
Pressor Response ◽  
Intrathecal Injection ◽  
Sensory Nerve ◽  
Lumbar Spinal Cord ◽  
Exercise Pressor Reflex ◽  
Static Contraction ◽  
Before And After ◽  
Pressor Reflex ◽  
Lumbar Spinal

We tested the hypothesis that oxytocin (Oxt) acts in the lumbar spinal cord to attenuate reflex pressor (mean arterial pressure, MAP) and heart rate (HR) responses to static hindlimb contraction (i.e., the exercise pressor reflex). Thus we compared MAP and HR responses to electrically stimulated hindlimb static contraction in the anesthetized cat before and after intrathecal injection of Oxt (30 pmol, n = 3; 300 pmol, n = 6; or 3 nmol, n = 6). The 300-pmol dose was most effective; it attenuated the pressor response to static contraction by 39 +/- 10% but had no effect on HR. In three other cats, contraction-induced increases in MAP and HR were monitored before and after intrathecal injection of 300 pmol of Oxt + 300 nmol of the selective Oxt receptor antagonist [d(CH2)5(1),O-Me-Tyr2,Thr4,Tyr9,Orn8]vasotocin. Pretreatment with the antagonist eliminated the effect of Oxt on MAP. In an additional 10 cats, increases in these same variables in response to static contraction were compared before and after intrathecal injection of the Oxt antagonist (30 nmol, n = 3 or 300 nmol, n = 7) into the lumbar spinal cord (L1-L7). Whereas 30 nmol of the Oxt antagonist had no effect, the 300-nmol dose augmented the contraction-induced pressor and HR responses by 28 +/- 7 and 32 +/- 17%, respectively. These data imply that endogenous Oxt modulates the exercise pressor reflex by its action on Oxt receptors in the lumbar spinal cord that can attenuate sensory nerve transmission from skeletal muscle.

Evidence of impaired hypoxic vasodilation after intermediate-duration hypoxic exposure in humans

2006 ◽  
Vol 291 (5) ◽  
pp. H2173-H2180 ◽  
Author(s):  
Geoffrey Gilmartin ◽  
Renaud Tamisier ◽  
Amit Anand ◽  
David Cunnington ◽  
J. Woodrow Weiss
Keyword(s):  
Vascular Resistance ◽  
Muscle Sympathetic Nerve Activity ◽  
Acute Hypoxia ◽  
Hypoxic Exposure ◽  
Burst Frequency ◽  
Ventilatory Parameters ◽  
Before And After ◽  
System Activation ◽  
Forearm Vascular Resistance

Systemic hemodynamics, including forearm blood flow and ventilatory parameters, were evaluated in 21 subjects before and after exposure to 8 h of poikilocapnic hypoxia. To evaluate the role of sympathetic nervous system activation in the changes, in 10 of these subjects, we measured muscle sympathetic nerve activity (MSNA) before and after exposure, and the remaining 11 subjects received intra-arterial phentolamine infusion in the brachial artery to define vascular tone in the absence of sympathetically mediated vasoconstriction. Short-term ventilatory acclimatization occurred as evidenced by a decrease in resting Pco2 (from 42 ± 1.4 to 37 ± 0.96 mmHg) and by an increase in the slope of the ventilatory response to acute hypoxia [from 0.7 ± 0.1 to 1.2 ± 0.2 l·min−1·%SpO2 (blood O2 saturation from pulse oximetry)] after exposure. Subjects demonstrated a significant increase in resting heart rate (from 61 ± 2 to 65 ± 2 beats/min) and diastolic blood pressure (from 64.8 ± 2.7 to 70.4 ± 2.0 mmHg). MSNA did not change significantly after exposure, although there was a trend toward a decrease in burst frequency (from 19.8 ± 4.1 to 14.3 ± 1.2 bursts/min). Forearm vascular resistance showed a significant decrease after termination of exposure (from 37.7 ± 3.6 to 27.6 ± 2.7 mmHg·ml−1·min·100 g tissue, P < 0.05). Initially, progressive isocapnic hypoxia elicited significant vasodilation, but after 8 h of poikilocapnic hypoxic exposure, the acute challenge failed to change forearm vascular resistance. Local α-blockade with phentolamine restored the vasodilatory response to acute hypoxia in the postexposure setting.

scholarly journals Local prostaglandin blockade attenuates muscle mechanoreflex-mediated renal vasoconstriction during muscle stretch in humans

2008 ◽  
Vol 294 (5) ◽  
pp. H2184-H2190 ◽  
Author(s):  
Afsana Momen ◽  
Jian Cui ◽  
Patrick McQuillan ◽  
Lawrence I. Sinoway
Keyword(s):  
Animal Studies ◽  
Duplex Ultrasound ◽  
Muscle Stretch ◽  
Renal Vasoconstriction ◽  
Block Trial ◽  
Before And After ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Muscle Mechanoreflex ◽  
Exercise Muscle ◽  
Bier Block

During exercise, muscle mechanoreflex-mediated sympathoexcitation evokes renal vasoconstriction. Animal studies suggest that prostaglandins generated within the contracting muscle sensitize muscle mechanoreflexes. Thus we hypothesized that local prostaglandin blockade would attenuate renal vasoconstriction during ischemic muscle stretch. Eleven healthy subjects performed static handgrip before and after local prostaglandin blockade (6 mg ketorolac tromethamine infused into the exercising forearm) via Bier block. Renal blood flow velocity (RBV; Duplex Ultrasound), mean arterial pressure (MAP; Finapres), and heart rate (HR; ECG) were obtained during handgrip, post-handgrip muscle ischemia (PHGMI) followed by PHGMI with passive forearm muscle stretch (PHGMI + stretch). Renal vascular resistance (RVR, calculated as MAP/RBV) was increased from baseline during all paradigms except during PHGMI + stretch after the ketorolac Bier block trial where RVR did not change from baseline. Before Bier block, RVR rose more during PHGMI + stretch than during PHGMI alone ( P < .01). Similar results were found after a saline Bier block trial (Δ53 ± 13% vs. Δ35 ± 10%; P < 0.01). However, after ketorolac Bier block, RVR was not greater during PHGMI + stretch than during PHGMI alone [Δ39 ± 8% vs. Δ40 ± 12%; P = not significant (NS)]. HR and MAP responses were similar during PHGMI and PHGMI + stretch ( P = NS). Passive muscle stretch during ischemia augments renal vasoconstriction, suggesting that ischemia sensitizes mechanically sensitive afferents. Inhibition of prostaglandin synthesis eliminates this mechanoreceptor sensitization-mediated constrictor responses. Thus mechanoreceptor sensitization in humans is linked to the production of prostaglandins.

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