Blockade of 5-HT3 receptors at septal area increase blood pressure in unanaesthetized rats

In the present study the role of 5-HT3 receptors located at the medial septum/vertical limb of the diagonal band complex (MS/vDB) in the control of blood pressure in unanaesthetized rats was investigated. Microinjections of ondansetron, a selective 5-HT3 receptor antagonist, into this area caused a dose-dependent increase in blood pressure. This rise was attenuated by the blockade of alpha-adrenoceptors with i.v. prazosin and blunted by the prior microinjection of losartan, an AT1 antagonist, into this brain area. Microinjections of the 5-HT3 agonist m-CPBG into this area failed to have any effect on blood pressure in non-stressed rats but significantly reduced the stress-induced hypertensive response. The reflex bradycardia evoked by i.v. phenylephrine was significantly increased after microinjections of ondansetron into this brain area but not the tachycardia evoked by i.v. sodium nitroprusside, suggesting that the pressor part of baroreflex has been enhanced. The data suggest that 5-HT3 receptors at this brain level exert a tonic sympathoinhibitory action that is mediated via the local release of angiotensin in the MS/vDB. This tonic 5-HT3 receptor drive also exerts an inhibitory action on the pressor component of the baroreflex. Also, the present data show that 5-HT3 receptors located in the MS/vDB participate in the regulation of stress-induced hypertensive response.