Microdialyzed adenosine in nucleus tractus solitarii and ventilatory response to hypoxia in piglets

Abstract

Levels of adenosine, inosine, and hypoxanthine from the interstitial space at the nucleus tractus solitarii were measured by microdialysis in eight 20- to 25-day-old anesthetized spontaneously breathing piglets. Microdialyzed samples were collected every 30 min for 2 h after the insertion of the probe to ensure stability of purine levels and then during 30 min each of normoxia, hypoxia (10% O2-90% N2), and normoxia. The purines were separated by high-pressure liquid chromatography with ultraviolet detection and quantified at 254-nm wavelength. Tidal volume, breathing frequency, minute ventilation, mean arterial blood pressure, pH, and gas tensions were measured. Compared with control, adenosine levels during hypoxia increased by 40.7 +/- 5.5% and then tended to decline during the recovery from hypoxia, but the levels remained higher than in control. Ventilatory measures exhibited a modest biphasic pattern during hypoxia and resumed control values by 10 min after the removal of the hypoxia. The increased adenosine release during hypoxia provides additional evidence for the possible participation of adenosine in the central suppression of breathing during hypoxia.

Vasopressin V1 receptors contribute to hemodynamic and sympathoinhibitory responses evoked by stimulation of adenosine A2a receptors in NTS

“…In both situations, decreases in MAP are accompanied by decreases in HR and RSNA and sustained increases in pre-ASNA (34,35,44). The similarities between the patterns of the responses may be physiologically relevant because adenosine is released into the central nervous system, including the NTS, during hypoxia, ischemia, and severe hemorrhage (26,43,46). Consistent with this concept, our preliminary data showed that blockade of adenosine receptors attenuates the bradycardic and sympathoinhibitory responses to severe hemorrhage (38).…”

P2Y1Receptor Modulation of the Pre-Bötzinger Complex Inspiratory Rhythm Generating NetworkIn Vitro

“…In respiratory networks, adenosine is clinically significant because it depresses ventilation (Herlenius et al, 1997;Herlenius and Lagercrantz, 1999;Mironov et al, 1999), and is implicated in the hypoxia-induced depression of ventilation (Yan et al, 1995) and apnea in newborns (Runold et al, 1989;Lopes et al, 1994). Our observation that the post-ATP decrease in frequency depends on ATP breakdown suggests that effects of ATP on rhythm will be determined by an interaction between P2 and P1 receptors.…”

Activation of NTS A1adenosine receptors inhibits regional sympathetic responses evoked by activation of cardiopulmonary chemoreflex

“…The primary natural source of adenosine is ATP released from nerve terminals and glial cells, which is subsequently catabolized to adenosine by ectonucleotidases (46,63,74). Importantly, adenosine is also released into extracellular space during life-threatening homeostasis imbalance such as hypoxia, ischemia, and severe hemorrhage; in these pathological situations adenosine results from massive catabolism of intracellular ATP (45,61, 69,72,73). Inasmuch as the most basic, life-supporting, reflexes (cardiovascular, respiratory, and other autonomic reflexes) are primarily integrated in the NTS (17), it is not surprising that the greatest density of adenosine uptake sites in the entire central nervous system is located in the NTS (6).…”