Involvement of central 5-HT7 receptors in modulation of cardiovascular reflexes in awake rats

This study evaluated the role of 5-HT7 receptors within the central nervous system in modulating cardiovascular responses to the activation of chemo-, baro- and cardiopulmonary reflexes and in the regulation of mean arterial pressure and heart rate, using intracisternal (i.c.) application of the selective 5-HT7 receptor antagonist SB-269970 in awake rats. Experiments were performed on male Wistar rats (300-320 g). At 4 days before the experiment, rats were anesthetized and placed in a stereotaxic frame implantation of a guide cannula in the direction of the cisterna magna to be used for microinjection of saline or SB-269970 (100 microg/kg). On the day before the experiments a femoral artery and vein were cannulated to record arterial pressure and heart rate and to inject drugs to activate cardiovascular reflexes, respectively. The chemo-, baro- and cardiopulmonary reflexes were activated in different experimental groups before and after i.c. injection of saline or SB-269970. The antagonism of 5-HT7 receptors reduced: (a) the pressor (50+/-4 vs. 19+/-9 mm Hg) and bradycardic (-247+/-13 vs. -69+/-27 bpm) responses to chemoreflex activation; (b) the fall in MAP (-54+/-4 vs. -20+/-6 mm Hg) and the bradycardia (-294+/-12 vs. -98+/-34 bpm) in response to cardiopulmonary reflex activation; and (c) the gain of the baroreflex (-2.3+/-0.1 to -0.9+/-0.2 bpm/mm Hg). Intracisternal application of SB-269970 increased significantly baseline MAP in those rats previously submitted to the activation of a cardiovascular reflex but in naïve rats produced no changes in the baseline MAP were observed. The fact that cardiovascular responses to all reflexes tested were attenuated by the antagonism of 5-HT7 receptors suggests that brainstem 5-HT7 receptors brainstem facilitate the processing of the autonomic responses to cardiovascular reflex activation and that a 5-HT-containing pathway to the brainstem provides a normalizing input during challenges produced by cardiovascular reflex activation which seems to be mediated by 5-HT7 receptors.