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

Abstract

In the present study the role of 5-HT(3) 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-HT(3) 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-HT(3) 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-HT(3) 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-HT(3) receptor drive also exerts an inhibitory action on the pressor component of the baroreflex. Also, the present data show that 5-HT(3) receptors located in the MS/vDB participate in the regulation of stress-induced hypertensive response.

Lateral septal area α1‐ and α2‐adrenoceptors differently modulate baroreflex activity in unanaesthetized rats

“…The facilitated tachycardic baroreflex response observed in the present study after the blockade of LSA α 2adrenoceptors was also observed after inhibition of other limbic structures, such as periaqueductal grey (Pelosi et al 2007) and diagonal band of Broca (Crestani et al 2008a;Urzedo-Rodrigues et al 2011). Moreover, similar reduction in baroreflex bradycardia observed after blockade of LSA α 1 -adrenoceptors was reported after ablation of the medial prefrontal cortex (Resstel et al 2004), insular cortex ), lateral hypothalamus (Inui et al 1995;Crestani et al 2009) and hypothalamic paraventricular nucleus (Crestani et al 2010a).…”

Multiple opioid receptors mediate the hypotensive response induced by central 5-HT3 receptor stimulation

“…central 5-HT 3 receptors by selective agonists blocks stressinduced hypertension (Ferreira et al, 2004). Additionally, we have shown that 5-HT 3 receptors located at the MS/vDB tonically inhibit sympathetic activity through an action mediated by angiotensinergic mechanisms in that same area (Urzedo-Rodrigues et al, 2011). The present study, confirm that a 5-HT 3 receptor-dependent mechanism seems to be part of the brain serotonergic system that contributes to cardiovascular regulation since the hypertensive response observed after ondansetron administration indicates that central 5-HT 3 receptors exert a tonic inhibitory drive on blood pressure.…”

“…We have previously demonstrated that central brain 5-HT 3 receptors exert tonic depressor effects on blood pressure in nonstressed rats, probably through a sympathoinhibitory-related mechanism (Ferreira et al, 2004). The effect of the 5-HT 3 agents on blood pressure control shown in that study may be partially explained by their action on the septal area, since when the same serotonergic agents were administered in the medial septum/ vertical limb of the diagonal band complex (MS/vDB), 5-HT 3 receptors located in this area were also shown to exert a tonic sympathoinhibitory effect that seems to be mediated by an angiotensinergic-dependent mechanism (Urzedo-Rodrigues et al, 2011). Furthermore, it has also been shown that activation of central 5-HT 2C receptors induces hypertension in non-stressed rats and that the functional integrity of those receptors is essential for the rise in blood pressure that occurs in the course of restraint stress (Ferreira et al, 2005).…”

Antidepressant treatment decreases daily salt intake and prevents heart dysfunction following subchronic aortic regurgitation in rats

“…Central 5-HT neurotransmission is also involved in the cardiovascular control. Interestingly, prosencephalic activation of the 5-HT3 agonist receptor exerts an inhibitory action on the pressor part of the baroreflex function [10]. Healthy individuals with family histories of coronary arterial disease receiving PAR treatment presented with lower blood pressure during psychosocial stress tests, suggesting a cardio-protective effect [20].…”

“…Panic patients treated with the SSRI paroxetine (PAR) present with increased heart rate variability [9]. The administration of a selective 5-HT 3 receptor agonist in the forebrain exerts a tonic sympathoinhibitory action on the pressor component of the baroreflex [10], suggesting a potential beneficial role for SSRI treatment in heart disease. Sodium intake reductions are well recognized as important steps to improve both the clinical outcome and the quality of life of cardiac patients [11,12].…”