Age protects from harmful effects produced by chronic intermittent hypoxia.

Obstructive sleep apnoea (OSA) affects an estimated 3­7% of the adult population, the frequency doubling at ages >60­65 years. As it evolves, OSA becomes frequently associated with cardiovascular, metabolic and neuropsychiatric pathologies defining OSA syndrome (OSAS). Exposing experimental animals to chronic intermittent hypoxia (CIH) can be used as a model of the recurrent hypoxic and O2 desaturation patterns observed in OSA patients. CIH is an important OSA event triggering associated pathologies; CIH induces carotid body (CB)-driven exaggerated sympathetic tone and overproduction of reactive oxygen species, related to the pathogenic mechanisms of associated pathologies observed in OSAS. Aiming to discover why OSAS is clinically less conspicuous in aged patients, the present study compares CIH effects in young (3­4 months) and aged (22­24 months) rats. To define potential distinctive patterns of these pathogenic mechanisms, mean arterial blood pressure as the final CIH outcome was measured. In young rats, CIH augmented CB sensory responses to hypoxia, decreased hypoxic ventilation and augmented sympathetic activity (plasma catecholamine levels and renal artery content and synthesis rate). An increased brainstem integration of CB sensory input as a trigger of sympathetic activity is suggested. CIH also caused an oxidative status decreasing aconitase/fumarase ratio and superoxide dismutase activity. In aged animals, CIH minimally affected CB responses, ventilation and sympathetic-related parameters leaving redox status unaltered. In young animals, CIH caused hypertension and in aged animals, whose baseline blood pressure was augmented, CIH did not augment it further. Plausible mechanisms of the differences and potential significance of these findings for the diagnosis and therapy of OSAS are discussed.

Experimental Observations on the Biological Significance of Hydrogen Sulfide in Carotid Body Chemoreception.

The cascade of transduction of hypoxia and hypercapnia, the natural stimuli to chemoreceptor cells, is incompletely understood. A particular gap in that knowledge is the role played by second messengers, or in a most ample term, of modulators. A recently described modulator of chemoreceptor cell responses is the gaseous transmitter hydrogen sulfide, which has been proposed as a specific activator of the hypoxic responses in the carotid body, both at the level of the chemoreceptor cell response or at the level of the global output of the organ. Since sulfide behaves in this regard as cAMP, we explored the possibility that sulfide effects were mediated by the more classical messenger. Data indicate that exogenous and endogenous sulfide inhibits adenyl cyclase finding additionally that inhibition of adenylyl cyclase does not modify chemoreceptor cell responses elicited by sulfide. We have also observed that transient receptor potential cation channels A1 (TRPA1) are not regulated by sulfide in chemoreceptor cells.

The Carotid Body Does Not Mediate the Acute Ventilatory Effects of Leptin.

Leptin is a hormone produced mostly in adipose tissue and playing a key role in the control of feeding and energy expenditure aiming to maintain a balance between food intake and metabolic activity. In recent years, it has been described that leptin might also contributes to control ventilation as the administration of the hormone reverses the hypoxia and hypercapnia commonly encountered in ob/ob mice which show absence of the functional hormone. In addition, it has been shown that the carotid body (CB) of the rat expresses leptin as well as the functional leptin-B receptor. Therefore, the possibility exists that the ventilatory effects of leptin are mediated by the CB chemoreceptors. In the experiments described below we confirm the stimulatory effect of leptin on ventilation, finding additionally that the CB does not mediate the instant to instant control of ventilation.