American journal of physiology. Regulatory, integrative and comparative physiology
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Feb 2011
Pathogen-induced heart rate changes associated with cholinergic nervous system activation.
The autonomic nervous system plays a central role in regulation of host defense and in physiological responses to sepsis, including changes in heart rate and heart rate variability. The cholinergic anti-inflammatory response, whereby infection triggers vagal efferent signals that dampen production of proinflammatory cytokines, would be predicted to result in increased vagal signaling to the heart and increased heart rate variability. In fact, decreased heart rate variability is widely described in humans with sepsis. ⋯ After recovery from the initial bradycardia, depressed heart rate variability developed in some mice and was correlated with elevated plasma cytokine levels and mortality. Our findings of decreased HRV and transient heart rate decelerations in infected mice are similar to heart rate changes described by our group in preterm neonates with sepsis. Pathogen sensing and signaling via the vagus nerve, and the desensitization of this response, may account for periods of both increased and decreased heart rate variability in sepsis.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Feb 2011
Hemodynamic responses to aortic depressor nerve stimulation in conscious L-NAME-induced hypertensive rats.
The present study investigated whether baroreflex control of autonomic function is impaired when there is a deficiency in NO production and the role of adrenergic and cholinergic mechanisms in mediating reflex responses. Electrical stimulation of the aortic depressor nerve in conscious normotensive and nitro-l-arginine methyl ester (L-NAME)-induced hypertensive rats was applied before and after administration of methylatropine, atenolol, and prazosin alone or in combination. The hypotensive response to progressive electrical stimulation (5 to 90 Hz) was greater in hypertensive (-27 ± 2 to -64 ± 3 mmHg) than in normotensive rats (-17 ± 1 to -46 ± 2 mmHg), whereas the bradycardic response was similar in both groups (-34 ± 5 to -92 ± 9 and -21 ± 2 to -79 ± 7 beats/min, respectively). ⋯ In conclusion, electrical stimulation produced a well-preserved baroreflex-mediated decrease in arterial pressure and heart rate in conscious l-NAME-induced hypertensive rats. Moreover, withdrawal of the sympathetic drive played a role in the reflex bradycardia only in hypertensive rats. The residual fall in pressure after the triple pharmacological blockade suggests the involvement of a vasodilatory mechanism unrelated to NO or deactivation of α(1)-adrenergic receptor.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Feb 2011
Electrostimulation during hindlimb unloading modulates PI3K-AKT downstream targets without preventing soleus atrophy and restores slow phenotype through ERK.
Our aim was to analyze the role of phosphatidylinositol 3-kinase (PI3K)-AKT and MAPK signaling pathways in the regulation of muscle mass and slow-to-fast phenotype transition during hindlimb unloading (HU). For that purpose, we studied, in rat slow soleus and fast extensor digitorum longus muscles, the time course of anabolic PI3K-AKT-mammalian target of rapamycin, catabolic PI3K-AKT-forkhead box O (FOXO), and MAPK signaling pathway activation after 7, 14, and 28 days of HU. Moreover, we performed chronic low-frequency soleus electrostimulation during HU to maintain exclusively contractile phenotype and so to determine more precisely the role of these signaling pathways in the modulation of muscle mass. ⋯ Taken together, our data demonstrated that the processes responsible for gradual disuse muscle plasticity in HU conditions involved both PI3-AKT and MAPK pathways. Moreover, electrostimulation during HU restored PI3K-AKT activation without counteracting soleus atrophy, suggesting the involvement of other signaling pathways. Finally, electrostimulation maintained initial contractile and metabolism properties in parallel to ERK activation, reinforcing the idea of a predominant role of ERK in the regulation of muscle slow phenotype.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Dec 2010
Diaphragm muscle shortening modulates kinematics of lower rib cage in dogs.
We tested the hypothesis that diaphragm muscle shortening modulates volume displacement and kinematics of the lower rib cage in dogs and that posture and mode of ventilation affect such modulation. Radiopaque markers were surgically attached to the lower three ribs of the rib cage and to the midcostal region of the diaphragm in six dogs of ∼8 kg body masses, and the locations of these markers were determined by a biplane fluoroscopy system. Three-dimensional software modeling techniques were used to compute volume displacement and surface area of the midcostal diaphragm and the lower three ribs during quiet spontaneous breathing, mechanical ventilation, and bilateral phrenic nerve stimulation at different lung volumes spanning the vital capacity. ⋯ In the prone posture, mechanical ventilation results in a smaller change in diaphragm surface area than spontaneous breathing (P < 0.05). Our data demonstrate that during inspiration the lower rib cage moves not only through the pump- and bucket-handle motion, but also rotates around the spine. Taken together, these data support the observation that the kinematics of the lower rib cage and its mechanical interaction with the diaphragm are more complex than previously known.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Nov 2010
Randomized Controlled Trial Multicenter StudyVentilatory restraint of sympathetic activity during chemoreflex stress.
The within-breath modulation of muscle sympathetic nerve activity (MSNA) is well established, with greater activity occurring during expiration and less during inspiration. Whether ventilation per se affects the longer-term (i.e., minute-to-minute) regulation of MSNA has not been determined. We sought to define the specific role of ventilation in regulating sympathetic activation during chemoreflex activation, where both ventilation and MSNA are increased. ⋯ The augmented sympathetic response during apneas was associated with a larger pressor response and total peripheral resistance compared with rebreathing. These data demonstrate that ventilation per se restrains sympathetic activation during chemoreflex activation. Further, the augmented sympathetic response during apneas was associated with greater cardiovascular stress and may be relevant to the cardiovascular pathology associated with sleep-disordered breathing.