Activation of lateral parabrachial nucleus neurons restores blood pressure and sympathetic vasomotor drive after hypotensive hemorrhage

Abstract

Lesions of the lateral parabrachial nucleus (LPBN) impair blood pressure recovery after hypotensive blood loss ( Am J Physiol Regul Integr Comp Physiol 280: R1141, 2001). This study tested the hypothesis that posthemorrhage blood pressure recovery is mediated by activation of neurons, located in the ventrolateral aspect of the LPBN (VL-LPBN), that initiates blood pressure recovery by restoring sympathetic vasomotor drive. Hemorrhage experiments (16 ml/kg over 22 min) were performed in unanesthetized male Sprague-Dawley rats prepared with bilateral ibotenate lesions or guide cannulas directed toward the external lateral subnucleus of the VL-LPBN. Hemorrhage initially decreased mean arterial pressure (MAP) from ∼100 mmHg control to 40–50 mmHg, and also decreased heart rate. In animals with sham lesions, MAP returned to 84 ± 4 mmHg by 40 min posthemorrhage, and subsequent autonomic blockade with hexamethonium reduced MAP to 53 ± 2 mmHg. In contrast, animals with VL-LPBN lesions remained hypotensive at 40 min posthemorrhage (58 ± 4 mmHg) and hexamethonium had no effect on MAP, implying a deficit in sympathetic tone. VL-LPBN lesions did not alter the renin response or the effect of vasopressin V1 receptor blockade after hemorrhage. Posthemorrhage blood pressure recovery was also significantly delayed by VL-LPBN infusion of the ionotropic glutamate receptor antagonist kynurenic acid. Both VL-LPBN lesions and VL-LPBN kynurenate infusion caused posthemorrhage bradycardia to be significantly prolonged. Bradycardia was reversed by hexamethonium or atropine, but did not contribute to posthemorrhage hypotension. Taken together, these data support the hypothesis that stimulation of VL-LPBN glutamate receptors mediates spontaneous blood pressure recovery by initiating restoration of sympathetic vasomotor drive.