Role of A5 noradrenergic neurons in the chemoreflex control of respiratory and sympathetic activities in unanesthetized conditions.

The A5 area at the ventrolateral pons contains noradrenergic neurons connected with other medullary areas involved in the cardiorespiratory control. Its contribution to the cardiorespiratory regulation was previously evidenced in anesthetized conditions. In the present study, we investigated the involvement of the A5 noradrenergic neurons to the basal and chemoreflex control of the sympathetic and respiratory activities in unanesthetized conditions. A5 noradrenergic neurons were lesioned using microinjections of anti-dopamine ß-hydroxylase saporin (anti-DßH-SAP). After 7-8days, we evaluated the arterial pressure levels, heart rate and minute ventilation in freely moving adult rats (280-350g) as well as recorded from thoracic sympathetic (tSN) and phrenic nerves (PN) using the arterially perfused in situ preparation of juvenile rats (80-90g). Baseline cardiovascular, sympathetic and respiratory parameters were similar between control (n=7-8) and A5-lesioned rats (n=5-6) in both experimental preparations. In adult rats, lesions of A5 noradrenergic neurons did not modify the reflex cardiorespiratory adjustments to hypoxia (7% O2) and hypercapnia (7% CO2). In the in situ preparations, the sympatho-excitation, but not the PN reflex response, elicited by either the stimulation of peripheral chemoreceptors (ΔtSN: 110±12% vs 58±8%, P<0.01) or hypercapnia (ΔtSN: 9.5±1.4% vs 3.9±1.7%, P<0.05) was attenuated in A5-lesioned rats compared to controls. Our data demonstrated that A5 noradrenergic neurons are part of the circuitry recruited for the processing of sympathetic response to hypoxia and hypercapnia in unanesthetized conditions.

Molsidomine modulates the cNOS activity in an experimental model of cholinergic damage induced by 192-IgG saporin.

The aim of this work was to study the effect of molsidomine (MOLS), a nitric oxide (NO) donor, on the nitrergic system changes in an experimental model of cholinergic damage induced by 192 IgG saporin (SAP). Male rats were injured by intraseptal administration of SAP (0.22 µg), after seven days, rats were administered with MOLS (4 mg/kg, i.p.) 60 min before sacrifice. Prefrontal cortex (PC), striatum (S) and hippocampus (HC) were dissected out. Results showed significant recovery of the constitutive NOS activity (cNOS) in PC and S regions by MOLS but not in HC compared against controls. SAP reduced the cellular population in the lesion site and MOLS was able to avoid the progression of damage in this area. NO donor is able to modulate the nitrergic status in an experimental model induced by SAP.

Lesions of medullary catecholaminergic neurons increase salt intake in rats.

Several findings suggest that catecholaminergic neurons in the caudal ventrolateral medulla (CVLM) contribute to body fluid homeostasis and cardiovascular regulation. From the CVLM other areas in central nervous system involved in cardiovascular regulation and hydroelectrolyte balance can be activated. Therefore, the aim of the present study was to investigate the effects of lesions of these neurons on 0.3M NaCl and water intake induced by subcutaneous injection of furosemide (FURO)+captopril (CAP) or 36 h of water deprivation/partial hydration with only water (WD/PR). Male Wistar rats (320-360 g) were submitted to medullary catecholaminergic neuron lesions by microinjection of anti-dopamine-beta-hydroxylase-saporin (anti-DbetaH-saporin; 6.3 ng in 60 nl) into the CVLM (SAP-rats). Sham rats received microinjections of free saporin (1.3 ng in 60 nl) in the same region. In SAP-rats, the 0.3M NaCl intake was increased after FURO+CAP (6.8+/-1.0 ml/2h, vs. sham: 3.7+/-0.7 ml/2h) as well as after WD/PR (11.1+/-1.3 ml/2h vs. sham: 6.1+/-1.8 ml/2h). Conversely, in SAP-rats, the water intake induced by FURO+CAP (14.8+/-1.3 ml/2h, vs. sham: 14.1+/-1.6 ml/2h) or by WD/PR (3.6+/-0.9 ml/2h, vs. sham: 3.2+/-1.1 ml/2h) was not different from sham rats. Immunohistochemical analysis indicates that microinjections of anti-DbetaH-saporin produced extensive destruction within the A1 cell groups in the CVLM. These results suggest an inhibitory role for medullary catecholaminergic neurons on sodium appetite.