Myocardial ischemia evokes powerful reflex responses through activation of vagal and sympathetic afferents in the heart through the release of ischemic metabolites. We have demonstrated that extracellular ATP stimulates cardiac sympathetic afferents through P2 receptor-mediated mechanism, and that opioid peptides suppress these afferents’ activity. However, the roles of both P2 receptor and endogenous opioids in cardiac sympathoexcitatory reflex (CSR) responses remain unclear. We therefore hypothesized that activation of cardiac P2 receptor evokes CSR responses by stimulating cardiac sympathetic afferents and these CSR responses are modulated by endogenous opioids. We observed that intrapericardial injection of α,β-methylene ATP (α,β-meATP, P2X receptor agonist), but not ADP (P2Y receptor agonist), caused a graded increase in mean arterial pressure in rats with sinoaortic denervation and vagotomy. This effect of α,β-meATP was abolished by blockade of cardiac neural transmission with intrapericardial procaine treatment and eliminated by intrapericardial A-317491, a selective P2X2/3 and P2X3 receptor antagonist. Intrapericardial α,β-meATP also evoked CSR response in vagus-intact rats. Furthermore, the P2X receptor-mediated CSR responses were enhanced by intrapericardial naloxone, a specific opioid receptor antagonist. These data suggest that stimulation of cardiac P2X2/3 and P2X3, but not P2Y receptors, powerfully evokes CSR responses through activation of cardiac spinal afferents, and that endogenous opioids suppress the P2X receptor-mediated CSR responses.
Activation of cardiac spinal afferents evokes excitatory cardiovascular reflexes. We have demonstrated that extracellular ATP stimulates ischemia‐sensitive cardiac afferents through P2 receptor mechanisms. The present study tested the hypothesis that through activation of P2 receptors ATP provokes excitatory cardiovascular reflexes and the reflexes are facilitated by blockade of opioid receptors. Hemodynamic parameters were recorded in anesthetized rats after bilateral vagotomy. Intrapericardial injection of α,β‐meATP (31–500 nmol), a P2X receptor agonist, increased mean arterial pressure (MAP) by 4±2 to 49±4 mmHg in a dose‐dependent manner in seven rats. After blockade of cardiac neural transmission with intrapericardial procaine, the α,β‐meATPevoked pressor responses were almost eliminated (n=6). Application of α,β‐meATP‐evoked consistent reflexes in six control rats. Intrapericardial ADP, a P2Y receptor agonist, also increased MAP in five rats by 9 to 13±3 mmHg, although we observed no changes in two and a decrease in two rats. Finally, blockade of opioid receptors with naloxone enhanced the α,β‐meATP‐mediated reflexes from increase in MAP by 27±3 to 37±3 mmHg (n=6). These data suggest that extracellular ATP provokes cardiac sympathetic afferent reflexes mainly through P2X receptor mechanisms and that the magnitude of these reflexes is partially dependent on intact opioid receptors.
Background and Objectives:Few controlled trials on antibiotic therapy for small intestinal bacterial overgrowth are available at present. Aim of the study was to assess efficacy, safety and tolerability of rifaximin with respect to metronidazole for the treatment of small intestinal bacterial overgrowth.Material and Methods: We enrolled 142 consecutive patients with diagnosis of small intestinal bacterial overgrowth. Diagnosis of small intestinal bacterial overgrowth based on the clinical history and the positivity of glucose breath test. Patients were randomised to two 7-day treatment groups: rifaximin 1200 mg/day and metronidazole 750 mg/day. Glucose breath test was reassessed 1 month after. Compliance and side-effect incidence were also evaluated.Results: One drop-out was observed in rifaximin group. Five drops-out occurred in metronidazole group. The glucose breath test normalization rate was significantly higher in the rifaximin with respect to the metronidazole group (63.4% versus 43.7%; p<0.05; OR 1.50, 95% CI 1.14-4.38). The overall prevalence of adverse events was significantly lower in rifaximin with respect to metronidazole group. Discussion: Rifaximin showed an higher SIBO decontamination rate than metronidazole at the tested doses, both with a significant gain in terms of tolerability. Either the present study or recent evidencies suggest that rifaximin represents a good choice for the management of patients affected by SIBO.
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