[R-00144-2011 revised] Activation of 5-hydroxytryptamine 1a receptors suppresses cardiovascular responses evoked from the paraventricular nucleus

Activation of central 5-hydroxytryptamine 1A receptors powerfully inhibits stress-evoked cardiovascular responses mediated by the dorsomedial hypothalamus, as well as responses evoked by direct activation of neurons within the dorsomedial hypothalamus. The hypothalamic paraventricular nucleus 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 dorsomedial hypothalamus. In this study, we determined whether cardiovascular responses evoked from the paraventricular nucleus are also modulated by activation of central 5-hydroxytryptamine 1A receptors. In anesthetised rats, the increases in heart rate and renal sympathetic nerve activity evoked by bicuculline injection into the paraventricular nucleus were greatly reduced (by 54% and 61%, respectively), by intravenous administration of (±)-8-hydroxy-2-(din -propylamino)tetralin, an agonist of 5-hydroxytryptamine 1A receptors, but were then completely restored by subsequent administration of WAY-100635, a selective antagonist of 5-hydroxytryptamine 1A receptors. Microinjection of (±)-8-hydroxy-2-(din -propylamino)tetralin directly into the paraventricular nucleus did not significantly affect the responses to bicuculline injection into the paraventricular nucleus, nor did systemic administration of WAY-100635 alone. In control experiments, a large renal sympathoexcitatory response was evoked from both the paraventricular nucleus and dorsomedial hypothalamus but not from the intermediate region in between; thus the evoked responses from the paraventricular nucleus were not due to activation of neurons in the dorsomedial hypothalamus. The results indicate that activation of central 5-hydroxytryptamine 1A receptors located outside the paraventricular nucleus powerfully inhibits the tachycardia and renal sympathoexcitation evoked by stimulation of neurons in the paraventricular nucleus.