Effect of dynorphin microinjection in the anterior hypothalamus (AV3V) region on the hemodynamic response to hemorrhage in the rat.

The region surrounding the anteroventral part of the third ventricle (AV3V) is important for the regulation of cardiovascular homeostasis. In the present study we investigated the effect of the kappa-opioid receptor agonists dynorphin A-(1-17) and dynorphin A-(1-13) microinjected into the AV3V region on mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), and left ventricular stroke work (LVSW) during fixed-volume hemorrhage in conscious rats. During fixed-volume hemorrhage (8 ml/300 g), dynorphin A-(1-17) (6 nmol), microinjected into the AV3V, significantly decreased MAP up to 30 min postinjection (P < 0.05). Recovery of MAP, SV, and LVSW in the dynorphin A-(1-17) group following hemorrhage was found to be significantly attenuated compared to that in animals receiving microinjection of normal saline (NS) vehicle into the AV3V (P < 0.05). Hypothalamic microinjection of dynorphin A-(1-13) (6 nmol) also attenuated the recovery of SV following hemorrhage compared with the NS group (P < 0.05). No significant effects were observed on HR or CO following microinjection of dynorphin into the AV3V region. The results of this study suggest that activation of the kappa-opiate receptor system in the AV3V region of the hypothalamus can attenuate the compensatory cardiovascular responses to hemorrhage.