American journal of physiology. Regulatory, integrative and comparative physiology
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Mar 2011
Activation of CaMKII and ERK1/2 contributes to the time-dependent potentiation of Ca2+ response elicited by repeated application of capsaicin in rat DRG neurons.
When capsaicin is applied repeatedly to dorsal root ganglion (DRG) neurons for brief periods (10-15 s) at short intervals (5-10 min), the evoked responses rapidly decline, a phenomenon termed tachyphylaxis. In addition to this phenomenon, the present study using Ca(2+) imaging revealed that repeated application of capsaicin to rat dissociated DRG neurons at longer intervals (20-40 min) or during multiple applications at short intervals elicited an enhancement of the responses, termed potentiation. The potentiation occurred in 50-60% of the capsaicin-responsive cells, on average representing a 20- to 30% increase in the peak amplitude of the Ca(2+) signal, and was maximal at a 40-min application interval. ⋯ Potentiation was not affected by: 1) inhibition of protein kinase C or protein kinase A, 2) block of the three subtypes of neurokinin receptors, or 3) block of the trafficking of transient receptor potential V1 channel to the membrane. These results indicate that the potentiation is a slowly developing Ca(2+)-modulated process that is mediated by a complex intracellular signaling pathway involving activation of CaMKII and ERK1/2. Potentiation may be an important peripheral autosensitization mechanism that occurs independently of the pronociceptive effects of inflammatory mediators and neurotrophic factors.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Feb 2011
Controlled Clinical TrialModelflow underestimates cardiac output in heat-stressed individuals.
An estimation of cardiac output can be obtained from arterial pressure waveforms using the Modelflow method. However, whether the assumptions associated with Modelflow calculations are accurate during whole body heating is unknown. This project tested the hypothesis that cardiac output obtained via Modelflow accurately tracks thermodilution-derived cardiac outputs during whole body heat stress. ⋯ However, the increase in cardiac output estimated from the Modelflow method for both arterial cannulation (2.3 ± 1.1 l/min) and Finometer (1.5 ± 1.2 l/min) was attenuated compared with thermodilution (4.5 ± 1.4 l/min, both P < 0.01). Finally, the reduction in cardiac output during LBNP while heat stressed was significantly attenuated for both Modelflow methods (cannulation: -1.8 ± 1.2 l/min, Finometer: -1.5 ± 0.9 l/min) compared with thermodilution (-3.8 ± 1.19 l/min). These results demonstrate that the Modelflow method, regardless of Finometer or direct arterial waveforms, underestimates cardiac output during heat stress and during subsequent reductions in cardiac output via LBNP.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Feb 2011
Proteomic alterations of distinct mitochondrial subpopulations in the type 1 diabetic heart: contribution of protein import dysfunction.
Diabetic cardiomyopathy is associated with increased risk of heart failure in type 1 diabetic patients. Mitochondrial dysfunction is suggested as an underlying contributor to diabetic cardiomyopathy. Cardiac mitochondria are characterized by subcellular spatial locale, including mitochondria located beneath the sarcolemma, subsarcolemmal mitochondria (SSM), and mitochondria situated between the myofibrils, interfibrillar mitochondria (IFM). ⋯ Mitochondrial protein import was decreased in the diabetic IFM with no change in the diabetic SSM (P < 0.05). Taken together, these results indicate that mitochondrial proteomic alterations in the type 1 diabetic heart are more pronounced in the IFM. Further, proteomic alterations are associated with nuclear encoded mitochondrial protein import dysfunction and loss of an essential mitochondrial protein import constituent, mtHsp70, implicating this process in the pathogenesis of the diabetic heart.
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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.