Activation of 5-hydroxytryptamine-1A receptors suppresses cardiovascular responses evoked from the paraventricular nucleus.
ABSTRACT Activation of central 5-hydroxytryptamine-1A (5-HT(1A)) receptors powerfully inhibits stress-evoked cardiovascular responses mediated by the dorsomedial hypothalamus (DMH), as well as responses evoked by direct activation of neurons within the DMH. The hypothalamic paraventricular nucleus (PVN) also has a crucial role in cardiovascular regulation and is believed to regulate heart rate and renal sympathetic activity via pathways that are independent of the DMH. In this study, we determined whether cardiovascular responses evoked from the PVN are also modulated by activation of central 5-HT(1A) receptors. In anesthetized rats, the increases in heart rate and renal sympathetic nerve activity evoked by bicuculline injection into the PVN were greatly reduced (by 54% and 61%, respectively) by intravenous administration of (±)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), an agonist of 5-HT(1A) receptors, but were then completely restored by subsequent administration of WAY-100635, a selective antagonist of 5-HT(1A) receptors. Microinjection of 8-OH-DPAT directly into the PVN did not significantly affect the responses to bicuculline injection into the PVN, nor did systemic administration of WAY-100635 alone. In control experiments, a large renal sympathoexcitatory response was evoked from both the PVN and DMH but not from the intermediate region in between; thus the evoked responses from the PVN were not due to activation of neurons in the DMH. The results indicate that activation of central 5-HT(1A) receptors located outside the PVN powerfully inhibits the tachycardia and renal sympathoexcitation evoked by stimulation of neurons in the PVN.
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ABSTRACT: Circulating angiotensin II (Ang II) combined with high salt intake increases sympathetic nerve activity (SNA) in some forms of hypertension. Ang II-induced increases in SNA are modest, delayed, and specific to certain vascular beds. The brain targets for circulating Ang II are neurons in the area postrema (AP), subfornical organ (SFO), and possibly other circumventricular organs. Ang II signaling is integrated with sodium-sensitive neurons in the SFO and/or organum vasculosum of the lamina terminalis (OVLT) and drives sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM) via the paraventricular nucleus (PVN). It is likely that, over time, new patterns of gene expression emerge within neurons of the SFO-PVN-RVLM pathway that transform their signaling properties. This transformation is critical in maintaining increased SNA. Identification of a novel gene supporting this process may provide new targets for treatment of neurogenic hypertension.Current Hypertension Reports 07/2007; 9(3):228-35. · 3.74 Impact Factor