American journal of physiology. Heart and circulatory physiology
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Am. J. Physiol. Heart Circ. Physiol. · Jul 2013
Exercise training normalizes the blunted central component of the baroreflex in rats with heart failure: role of the PVN.
Exercise training (ExT) normalizes the increased sympathetic outflow in chronic heart failure (HF). The underlying mechanisms are not clearly understood. We hypothesized that ExT normalized the blunted central component of the baroreflex control of renal sympathetic nerve activity (RSNA) in HF. ⋯ Activation of the PVN by blockade of GABA receptors with bicuculline in normal control rats blunted the centrally component of the baroreflex arc. GABAA-α1 and -β1 receptor protein expression were significantly lower (by 48% and 30%) in the HF-Sed group, but ExT normalized this difference between the HF and sham groups. These data suggest that one mechanism by which ExT alleviates elevated sympathetic outflow in HF may be through normalization of central integrative mechanisms, perhaps via improving the inhibitory GABAergic mechanism within the PVN, on the baroreflex arc.
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Am. J. Physiol. Heart Circ. Physiol. · Jun 2013
Middle cerebral O₂ delivery during the modified Oxford maneuver increases with sodium nitroprusside and decreases during phenylephrine.
The modified Oxford maneuver is the reference standard for assessing arterial baroreflex function. The maneuver comprises a systemic bolus injection of 100 μg sodium nitroprusside (SNP) followed by 150 μg phenylephrine (PE). On the one hand, this results in an increase in oxyhemoglobin and total hemoglobin followed by a decrease within the cerebral sample volume illuminated by near-infrared spectroscopy (NIRS). ⋯ SNP increased ΔQa by 0.36 ± .03 μmol·kg(-1)·s(-1) (21.6 μmol·kg(-1)·min(-1)), whereas CBFv decreased from 71 ± 2 to 62 ± 2 cm/s. PE decreased ΔQa by 0.27 ± .2 μmol·kg(-1)·s(-1) (16.2 μmol·kg(-1)·min(-1)), whereas CBFv increased to 75 ± 3 cm/s. These results are consistent with dilation of the MCA by SNP and constriction by PE.
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Am. J. Physiol. Heart Circ. Physiol. · Jun 2013
Muscle metaboreflex activation speeds the recovery of arterial blood pressure following acute hypotension in humans.
It has been suggested that the arterial baroreflex and muscle metaboreflex are both activated during heavy exercise and that they interact to modulate primary cardiovascular reflex responses. This proposed interaction and its consequences are not fully understood, however. The purpose of present study was to test our hypothesis that dynamic arterial baroreflex-mediated cardiovascular responses to acute systemic hypotension in humans are augmented when the muscle metaboreflex is active and that this results in a faster recovery of arterial blood pressure. ⋯ In addition, arterial baroreflex-mediated peripheral vasoconstriction was augmented during PEMI, as evidenced by a near doubling of the rate of recovery of MAP and TVC. These results show that when the muscle metaboreflex is activated in humans, arterial baroreflex-mediated peripheral vasoconstriction elicited in response to acute hypotension is augmented, which halves the time needed for MAP recovery. Such modulation of baroreflex function would be advantageous for maintaining an elevated arterial blood pressure during activation of the muscle metaboreflex.
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Am. J. Physiol. Heart Circ. Physiol. · May 2013
Hydrogen sulfide preconditions the db/db diabetic mouse heart against ischemia-reperfusion injury by activating Nrf2 signaling in an Erk-dependent manner.
Hydrogen sulfide (H2S) therapy protects nondiabetic animals in various models of myocardial injury, including acute myocardial infarction and heart failure. Here, we sought to examine whether H2S therapy provides cardioprotection in the setting of type 2 diabetes. H2S therapy in the form of sodium sulfide (Na2S) beginning 24 h or 7 days before myocardial ischemia significantly decreased myocardial injury in db/db diabetic mice (12 wk of age). ⋯ This discrepancy was found to be the result of an increased nuclear expression of Bach1, a known repressor of HO-1 transcription, which blocked the binding of Nrf2 to the HO-1 promoter. Further analysis revealed that 7 days of Na2S treatment overcame this impairment by removing Bach1 from the nucleus in an Erk1/2-dependent manner. Our findings demonstrate for the first time that exogenous administration of Na2S attenuates myocardial ischemia-reperfusion injury in db/db mice, suggesting the potential therapeutic effects of H2S in treating a heart attack in the setting of type 2 diabetes.
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Am. J. Physiol. Heart Circ. Physiol. · Apr 2013
Reduction of cardiomyocyte S-nitrosylation by S-nitrosoglutathione reductase protects against sepsis-induced myocardial depression.
Myocardial depression is an important contributor to morbidity and mortality in septic patients. Nitric oxide (NO) plays an important role in the development of septic cardiomyopathy, but also has protective effects. Recent evidence has indicated that NO exerts many of its downstream effects on the cardiovascular system via protein S-nitrosylation, which is negatively regulated by S-nitrosoglutathione reductase (GSNOR), an enzyme promoting denitrosylation. ⋯ GSNOR overexpression however significantly reduced total cardiac protein S-nitrosylation during sepsis. Taken together, our results indicate that increasing the denitrosylation capacity of cardiomyocytes protects against sepsis-induced myocardial depression. Our findings suggest that specifically reducing protein S-nitrosylation during sepsis improves cardiac function by increasing cardiac myofilament sensitivity to Ca(2+).