Carotid sinus nerve stimulation, but not intermittent hypoxia, induces respiratory LTF in adult rats exposed to neonatal intermittent hypoxia

Abstract

Julien CA, Niane L, Kinkead R, Bairam A, Joseph V. Carotid sinus nerve stimulation, but not intermittent hypoxia, induces respiratory LTF in adult rats exposed to neonatal intermittent hypoxia. Am J Physiol Regul Integr Comp Physiol 299: R192-R205, 2010. First published April 21, 2010 doi:10.1152/ajpregu.00707.2009.-We tested the hypothesis that exposure to neonatal intermittent hypoxia (n-IH) in rat pups alters central integrative processes following acute and intermittent peripheral chemoreceptor activation in adults. Newborn male rats were exposed to n-IH or normoxia for 10 consecutive days after birth. We then used both awake and anesthetized 3-to 4-mo-old rats to record ventilation, blood pressure, and phrenic and splanchnic nerve activities to assess responses to peripheral chemoreflex activation (acute hypoxic response) and long-term facilitation (LTF, long-term response after intermittent hypoxia). In anesthetized rats, phrenic and splanchnic nerve activities and hypoxic responses were also recorded with or without intact carotid body afferent signal (bilateral chemodenervation) or in response to electrical stimulations of the carotid sinus nerve. In awake rats, n-IH alters the respiratory pattern (higher frequency and lower tidal volume) and increased arterial blood pressure in normoxia, but the ventilatory response to repeated hypoxic cycles was not altered. In anesthetized rats, phrenic nerve responses to repeated hypoxic cycles or carotid sinus nerve stimulation were not altered by n-IH; however, the splanchnic nerve response was suppressed by n-IH compared with control. In control rats, respiratory LTF was apparent in anesthetized but not in awake animals. In n-IH rats, respiratory LTF was not apparent in awake and anesthetized animals. Following intermittent electrical stimulation, however, phrenic LTF was clearly present in n-IH rats, being similar in magnitude to controls. We conclude that, in adult n-IH rats: 1) arterial blood pressure is elevated, 2) peripheral chemoreceptor responses to hypoxia and its central integration are not altered, but splanchnic nerve response is suppressed, 3) LTF is suppressed, and 4) the mechanisms involved in the generation of LTF are still present but are masked most probably as the result of an augmented inhibitory response to hypoxia in the central nervous system. neonatal intermittent hypoxia; long-term facilitation DEVELOPMENT OF THE RESPIRATORY control system is tightly regulated by complex interactions between genetic and environmental factors that contribute to shape the mature phenotypic expression of this neural network (4). Over the past years, several studies have documented that alterations in environmental oxygen levels during development lead to important changes of the respiratory control system (4). A particular importance has been given to intermittent hypoxic exposure (38, 47, 50) because it may be used in laboratory animals to reproduce some of the effects encountered in human newborn suffering from apneas, which remains one of the major cause...

Systemic blockade of nicotinic and purinergic receptors inhibits ventilation and increases apnoea frequency in newborn rats

“…Set‐up details All of the ventilatory recordings were made using non‐invasive whole‐body flow‐through plethysmography (Emka Technologies, Paris, France) according to a procedure we have previously described (Julien et al 2010, 2011; Niane et al 2011; Niane & Bairam, 2011). Awake rats were placed inside the plethysmograph chamber (inner volume 0.22 litres for P4 and 0.75 litres for P12 pups) under a constant airflow (0.1 l min −1 for P4 and 0.2 l min −1 for P12), which was monitored with a mass flowmeter (4140; TSI, Shoreview, MN, USA).…”

“…Before the recording, the gas analysers were calibrated according to the manufacturer's specifications (AEI Technologies, Naperville, IL, USA). The oxygen consumption ( ) was calculated as flow × (O 2in – O 2out ) – (O 2out × (CO 2out – CO 2in )/(1 – O 2out ), and carbon dioxide production ( ) was calculated as flow × (CO 2out – CO 2in ) – (CO 2out × (O 2in – O 2out )/(1 – CO 2out ), corrected to standard temperature and pressure in dry (STPD) conditions and expressed per 100 g of body weight (Julien et al 2010; Niane et al 2011). These values were then used for the calculation of the ventilatory equivalents for oxygen ( ) and carbon dioxide ( ).…”

Ovariectomy at 3 or 10 weeks of age does not affect the ventilatory response to hypoxia in adult rats

“…Rats were supplied with food and water ad libitum and maintained under standard animal care conditions (21˚C, 12 h:12 h dark:light cycle, lights on at 8:00 A.M. and off at 8:00 P.M.). Mating, litter manipulation, surveillance and ventilatory recording using whole body, flow-through plethysmography were all performed according to our standard procedures, which have been previously described in detail [6,7]. Ventilatory parameters were first recorded under baseline ventilation (FiO 2 = 21%) for 10 min, and rats were then exposed to moderate hypoxia (FiO 2 = 12%) for 20 min.…”

“…Breathing frequency (fr/ min) and tidal volume (Vt ml BTPS/100 g) were measured using data acquisition software (IOX, EMKA Technologies, Falls Church, VA, USA) and were used to calculateminute ventilation (V E = fr × V T ml/min/100g). Barometric pressure, chamber temperature, and humidity were measured to correct V T as previously described [6,7]. The flow of gas into the plethysmography chamber was maintained constant at 2.0 L/min.…”

“…The flow of gas into the plethysmography chamber was maintained constant at 2.0 L/min. The oxygen concentration flowing in and out of the chamber was continuously measured (Oxygen analyzer model S-3A, Ametek, Pittsburgh, PA, USA) and used for subsequent calculations of oxygen consumption (VO 2 = ml/min/100 g) [6,7]. Oxygen consumption was assessed at baseline and at the end of the hypoxic exposure.…”