Chronic intermittent hypoxia (CIH), a main feature of obstructive sleep apnoea (OSA), increases hypoxic ventilatory responses and elicits hypertension, partially attributed to an enhance carotid body (CB) responsiveness to hypoxia. As inflammation has been involved in CIHinduced hypertension and chemosensory potentiation, we tested whether ibuprofen may block CB chemosensory and cardiorespiratory alterations induced by CIH in a rat model of OSA.We studied the effects of ibuprofen (40 mg?kg -1 ?day -1 ) on immunohistochemical interleukin (IL)-1b and tumour necrosis factor (TNF)-a levels in the CB, the number of c-fos-positive neurons in the nucleus tractus solitarii (NTS), CB chemosensory and ventilatory responses to hypoxia, and arterial blood pressure in male rats either exposed for 21 days to 5% O 2 (12 episodes?h ) or kept under sham condition. CIH increased CB TNF-a and IL-1b and c-fos-positive neurons in the NTS, enhanced carotid chemosensory and ventilatory hypoxic responses, and produced hypertension. Ibuprofen prevented CB cytokine overexpression and CIH-induced increases in c-fos-positive neurons in the NTS, the enhanced hypoxic ventilatory responses and hypertension, but failed to impede the CB chemosensory potentiation.Results suggest that pro-inflammatory cytokines may contribute to the CIH-induced cardiorespiratory alterations, acting at several levels of the hypoxic chemoreflex and cardiovascular control pathways. KEYWORDS: Hypertension, hypoxia, inflammation, obstructive sleep apnoea O bstructive sleep apnoea (OSA) syndrome, a rising worldwide health problem, is characterised by chronic intermittent hypoxia (CIH), which is considered the main risk factor for developing hypertension and other cardiovascular diseases [1][2][3]. It has been proposed that oxidative stress, inflammation and sympathetic activation are involved in OSA-induced hypertension [3][4][5][6]. A growing body of evidence suggests that CIH enhances carotid body (CB) chemosensory responses to hypoxia contributing to the OSA-induced hypertension [6][7][8][9]. Indeed, OSA patients and animals exposed to CIH show potentiated ventilatory, sympathetic and cardiovascular responses to acute hypoxia [6][7][8][9][10]. Furthermore, recordings of carotid chemosensory discharges in situ and in vitro have shown that CIH selectively increases basal chemosensory discharges in normoxia and potentiates the chemosensory responses to acute hypoxia in rats and cats [9,[11][12][13].The repetitive episodes of hypoxia-reoxygenation during CIH exposure elicits oxidative stress due to the accumulation of reactive oxygen species (ROS), which are involved in the potentiation of the hypoxic CB chemosensory responses [9,11,13,14] and in the pathological consequences observed in animals exposed to CIH, and in OSA patients [3-5, 8, 9, 13]. Recently, we found that ascorbic acid supplementation, which impedes the systemic and local CB oxidative stress in the rat exposed to CIH for 21 days, prevented enhanced CB chemosensory and ventilatory responses to h...

Drug craving critically depends on the function of the interoceptive insular cortex, and may be triggered by contextual cues. However, the role of the insula in the long-term memory linking context with drug craving remains unknown. Such a memory trace probably resides in some neocortical region, much like other declarative memories. Studies in humans and rats suggest that the insula may include such a region. Rats chronically implanted with bilateral injection cannulae into the high-order rostral agranular insular cortex (RAIC) or the primary interoceptive posterior insula (pIC) were conditioned to prefer the initially aversive compartment of a 2-compartment place preference apparatus by repeatedly pairing it to amphetamine. We found a reversible but long-lasting loss (ca. 24 days) of amphetamineconditioned place preference (CPP) and a decreased expression in the insula of zif268, a crucial protein in memory reconsolidation, when anisomycin (ANI) was microinjected into the RAIC immediately after the reactivation of the conditioned amphetamine/context memory. ANI infusion into the RAIC without reactivation did not change CPP, whereas ANI infusion into pIC plus caused a 15 days loss of CPP. We also found a 24 days loss of CPP when we reversibly inactivated pIC during extinction trials. We interpret these findings as evidence that the insular cortex, including the RAIC, is involved in a context/drug effect association. These results add a drug-related memory function to the insular cortex to the previously found role of the pIC in the perception of craving or malaise.

Chronic heart failure (CHF) is a major public health problem. Tonic hyper-activation of sympathetic neural outflow is commonly observed in patients with CHF. Importantly, sympatho-excitation in CHF exacerbates its progression and is strongly related to poor prognosis and high mortality risk. Increases in both peripheral and central chemoreflex drive are considered markers of the severity of CHF. The principal peripheral chemoreceptors are the carotid bodies (CBs) and alteration in their function has been described in CHF. Mainly, during CHF the CB chemosensitivity is enhanced leading to increases in ventilation and sympathetic outflow. In addition to peripheral control of breathing, central chemoreceptors (CCs) are considered a dominant mechanism in ventilatory regulation. Potentiation of the ventilatory and sympathetic drive in response to CC activation has been shown in patients with CHF as well as in animal models. Therefore, improving understanding of the contribution of the peripheral and central chemoreflexes to augmented sympathetic discharge in CHF could help in developing new therapeutic approaches intended to attenuate the progression of CHF. Accordingly, the main focus of this review is to discuss recent evidence that peripheral and central chemoreflex function are altered in CHF and that they contribute to autonomic imbalance and progression of CHF. Abstract figure legend Chronic heart failure is characterized by exacerbation of the peripheral and central chemoreflexes, which contributes to the establishment and progression of sympathoexcitation and breathing disorders. Importantly, chemoreflex activation is strongly associated with cardiac arrhythmogenesis, cardiac adverse remodelling, periodic breathing and central apnoeas and hypopnoeas.

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