BLOCKADE OF 5-HT 1A RECEPTORS IN THE PHRENIC NUCLEUS OF THE RAT ATTENUATED RAPHE INDUCED ACTIVATION OF THE PHRENIC NERVE ACTIVITY

INTRODUCTION A group of neurons in the medullary raphe nuclei is involved in respiratory control. Raphe neurons are known to be the major source of serotonergic projections to other respiratory areas of the brain stem and spinal cord (1-3). Previous studies have shown that stimulation of the neurons in the raphe pallidus (RP) produces excitatory effects on respiratory activity The basic respiratory behavior of anesthetized animals is attributed to phrenic nerve activity. The phrenic motor nucleus (PMN) receives descending serotonergic projections originating from the RP (3). These projections make important contributions to the changes in discharge patterns of the phrenic nerve activity. It has been shown that raphe induced respiratory facilitation of the phrenic nerve activity is attenuated following intravenous administration of the serotonergic receptor antagonist methysergide (3). Therefore, we hypothesized that chemical stimulation of RP would produce excitatory responses that are mediated through 5-HT 1A receptors in the PMN. The present study was performed to investigate changes in phrenic nerve activity with chemical stimulation of RP by the synaptic excitant, D,L-homocysteic acid (DLH). Additionally, this study examined the role of 5-HT 1A receptors in the PMN on the excitatory response elicited from RP. METHODS The protocol for this study was approved by the Ethical Committee for Biomedical Research of the University of Split School of Medicine, Split, Croatia. All experiments were carried out in accordance with the National Research Council's guide for the care and use of laboratory animals. General procedures Experiments were performed on adult male Sprague-Dawley rats weighing 280-330 g. Anesthesia was performed with intraperitoneal injection of 20% solution of urethane in 0.9% saline (1.2 g/kg; supplemental dose 0.2 g/kg). The adequacy of anesthesia was assessed by the absence of a withdrawal reflex after noxious paw pinch. The femoral vein and artery were cannulated for intravenous drug delivery, blood pressure monitoring, and sampling of arterial blood. Blood samples were taken at regular intervals, and arterial blood gasses were maintained within physiological limits by infusion of bicarbonate solution. The trachea was cannulated through midline incision. All animals were vagotomized bilaterally. End-JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2009, 60, 3, 167-172 www.jpp. Stimulation of the raphe pallidus nucleus produces facilitatory effects on respiratory activity. Numerous serotonergic projections from the raphe pallidus have been shown to terminate in the phrenic nucleus. This study was undertaken to examine the role of 5-hydroxytryptamine 1A (5-HT 1A ) receptors in the phrenic nucleus on the excitatory response of the phrenic nerve activity elicited from the raphe pallidus. We hypothesized that blockade of 5-HT 1A receptors in the phrenic nucleus will attenuate raphe-induced facilitation of the phrenic nerve. Chemical stimulation of the raphe pallidus by synaptic excitant D,L-homocysteic acid produced increase in the amplitude of the phrenic nerve activity. After microinjection of the specific 5-HT 1A receptor antagonist WAY, N-(2-(4,2-methoxyphenyl)-1-piperazinyl)ethyl)-N-2-pyridinyl-cyclohexane-carboxamide maleate into the phrenic nucleus, the raphe-induced facilitation of the phrenic nerve was attenuated. These data suggest that excitation of the phrenic nerve activity elicited by activation of the neurons in the raphe pallidus is mediated by 5-HT 1A receptors in the phrenic nucleus. K e y w o r d s : breathing, serotonin, phrenic nerve, ra

Arterial bicarbonate is associated with hypoxic burden and uncontrolled hypertension in obstructive sleep apnea - The ESADA cohort

Objective: Blood bicarbonate concentration plays an important role for obstructive sleep apnea (OSA) patients to maintain acid-base balance. We investigated the association between arterial standard bicarbonate ([HCO3-]) and nocturnal hypoxia as well as comorbid hypertension in OSA. Methods: A cross-sectional analysis of 3329 patients in the European Sleep Apnea Database (ESADA) was performed. Arterial blood gas analysis and lung function test were performed in conjunction with polysomnographic sleep studies. The 4% oxygen desaturation index (ODI), mean and minimum oxygen saturation (SpO2), and percentage of time with SpO2 below 90% (T90%) were used to reflect nocturnal hypoxic burden. Arterial hypertension was defined as a physician diagnosis of hypertension with ongoing antihypertensive medication. Hypertensive patients with SBP/DBP below or above 140/90 mmHg were classified as controlled-, uncontrolled hypertension, respectively. Results: The [HCO3-] level was normal in most patients (average 24.0 ± 2.5 mmol/L). ODI, T90% increased whereas mean and minimum SpO2 decreased across [HCO3-] tertiles (ANOVA, p = 0.030, <0.001, <0.001, and <0.001, respectively). [HCO3-] was independently associated with ODI, mean SpO2, minimum SpO2, and T90% after adjusting for confounders (β value [95%CI]: 1.21 [0.88–1.54], −0.16 [-0.20 to −0.11], −0.51 [-0.64 to −0.37], 1.76 [1.48–2.04], respectively, all p < 0.001). 1 mmol/L elevation of [HCO3-] was associated with a 4% increased odds of uncontrolled hypertension (OR: 1.04 [1.01–1.08], p = 0.013). Conclusion: We first demonstrated an independent association between [HCO3-] and nocturnal hypoxic burden as well as uncontrolled hypertension in OSA patients. Bicarbonate levels as an adjunctive measure provide insight into the pathophysiology of hypertension in OSA

Proposed cut-off points for optimal BMI, age and neck circumference value in the stop-bang: comparison of Greece, Turkey and Croatia

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