No abstract

The pontine nuclei, particularly the Kölliker-Fuse (KF) and the lateral parabrachial nucleus (LPBN) have been implicated in the maintenance of cardiorespiratory control. However, most of the experiments showing the role of pontine KF region were done in anesthetized animals. Here we investigated the involvement of KF region and LPBN in the cardiorespiratory responses elicited by chemoreceptor activation in conscious rats. Male Wistar rats (280-300g, n=5-9) with bilateral stainless steel guide-cannulas implanted into the KF region or LPBN were used. In conscious rats, injections of muscimol (100 and 200 pmol/100 nl) into the KF decreased resting ventilation (1140 ± 68 and 978 ± 100, vs. saline: 1436 ± 155 ml/kg/min) without change mean arterial pressure (MAP) and heart rate (HR). Bilateral injection of the GABA-A antagonist bicuculline (1 nmol/100 nl) into the KF blocked the inhibitory effect on ventilation (1418 ± 138, vs. muscimol: 978 ± 100 ml/kg/min) elicited by muscimol within the KF. Muscimol injection into the KF reduced the increase in ventilation produced by hypoxia (8% O 2 -10 min) (1827 ± 61, vs. saline: 3179 ± 325 ml/kg/min) or hypercapnia (7% CO 2 -10 min) (1488 ± 277, vs. saline: 3539 ± 374 ml/kg/min) in unanesthetized rats. Bilateral injection of bicuculline into the KF was able to block the decrease in ventilation produced by muscimol into the KF during peripheral or central chemoreflex activation. Bilateral injection of muscimol into the LPBN did not change resting ventilation, or the increase in ventilation elicited by hypoxia or hypercapnia. The injection of muscimol into the LPBN increased resting MAP (119 ± 2, vs. saline: 104 ± 2 mmHg), without change resting HR. Muscimol into the LPBN did not change the increase in ventilation elicited by hypoxia or hypercapnia in unanesthetized rats. Selective bilateral lesion with antidopamine-β-hydroxylase-saporin (anti-DβH-SAP) into the A7 region promoted a reduction of hyperventilation (1667 ± 180, vs. saline: 2209 ± 358 ml/kg/min), without changing the tachycardia (471 ± 18, vs. saline: 509 ± 12 bpm) elicited by hypoxia (8% O 2 -10 min) in unanesthetized rats. Bilateral injection of anti-DβH-SAP into the A7 region was able to attenuate the hypotension elicited by hypoxia (112 ± 3, vs. saline: 99 ± 5 mmHg). Anti-DβH-SAP into the A7 region was also able to reduce hyperventilation (1513 ± 167 vs saline: ± 144 2333 ml/kg/min) elicited by hypercapnia (7% CO2 -10 min) in unanesthetized rats. The results of the present study suggest that KF region, but not LPBN, have mechanisms to control the ventilation in resting, hypoxic or hypercapnic conditions in conscious rats.