Activation of 5HT1A receptors in the nucleus tractus solitarius contributes to blood pressure compensation with blood loss and peripheral chemoreflex responses in the presence of acidosis

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Caudal serotonin neurons and the 5‐HT1A receptor ( 1AR) agonist, 8‐OH‐DPAT, promote sympathetic‐mediated increases in cardiac output after blood loss. We hypothesize that the metabolic acidosis of hemorrhage activates serotonin neurons and 1AR in the nucleus tractus solitarius (NTS) to facilitate chemoreflex responses to carotid body hypoxia. Here, we tested ventilatory responses to hypoxic hypercapnia (10% O2, 5% CO2) and blood pressure responses to hemorrhage and subsequent 8‐OH‐DPAT administration in rats subjected to bilateral knockdown of the 1AR in the NTS. An adeno‐associated viral vector harboring a short hairpin RNA targeting the rat 1AR (1ARshRNA) or a scrambled shRNA (Scram) was injected into the caudal NTS of male Sprague Dawley rats. After 4 weeks, rats injected with the 1AshRNA (n=12) had lower cumulative minute ventilation during hypoxic hypercapnia vs. Scram‐injected rats (n=13, P<0.01). Rats injected with 1AshRNA (n=8) had a more rapid fall in blood pressure with blood loss and an attenuated blood pressure response to 8‐OH‐DPAT injection (30 nmol/kg, iv, P<0.01) vs. Scram‐injected rats (n=9). 1AshRNA injection decreased 1AR protein in the caudal NTS (−35%, P<0.05). Thus, the beneficial hemodynamic effect of 8‐OH‐DPAT and endogenous serotonin in hemorrhage is related to activation of 1AR in the NTS and possibly to facilitation of chemoreflex responses to hypoxia. Funded by AHA 10PRE4000023.