NEW FINDINGS: What is the central question of this study? Does antagonism of V1b receptors prevent the haemodynamic and renal sympathetic nerve responses that occur with application of exogenous vasopressin into the paraventricular nucleus (PVN) of conscious, chronically instrumented rats? What is the main finding and its importance? Microinjection of vasopressin into the PVN increased mean arterial pressure, heart rate and renal sympathetic nerve activity, all of which were inhibited by pre-injection of the PVN with the V1b antagonist, nelivaptan. The administered vasopressin did not enter the peripheral circulation or increase plasma vasopressin. Ganglionic blockade prevented each of the responses, consistent with mediation by enhanced sympathetic output rather than an increase in circulating vasopressin. Vasopressin (VP) participates in regulation of haemodynamics and volume. Besides more classical actions as a circulating hormone, VP may act via release from axons and dendrites within the CNS. The paraventricular nucleus (PVN) possesses vasopressinergic neurons and a dense complement of VP receptors, including the V1b receptor, which has been implicated in several types of stress responses. We tested the hypothesis that antagonism of V1b receptors will prevent VP-induced increases in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA). Studies were performed in conscious male Sprague-Dawley rats chronically instrumented with vascular catheters, renal nerve electrodes and a cannula stereotaxically directed into the PVN. Unilateral microinjection of VP into the PVN significantly increased MAP, HR and RSNA, peaking at 10 min. Pre-injection of the PVN with the selective V1b receptor antagonist, nelivaptan, did not alter baseline values but blocked the responses to VP. Ganglionic blockade with chlorisondamine decreased MAP and HR and abolished their increase in response to subsequent PVN application of VP. Injection of VP into the PVN did not alter plasma VP levels. Paraventricular nucleus injection with radiolabelled VP resulted in negligible radiolabelled VP in peripheral blood. These findings support the concept that, in basal conditions, PVN V1b receptor activation (rather than VP release into the periphery) may be implicated in the increases in MAP, HR and RSNA due to increased sympathetic outflow. While the role of V1a and oxytocin receptors cannot be excluded, these data suggest that further studies of the role of V1b receptor activation by endogenous VP during stress to effect neuroexcitation are warranted.
NEW FINDINGS: What is the central question of this study? Does antagonism of V1b receptors prevent the haemodynamic and renal sympathetic nerve responses that occur with application of exogenous vasopressin into the paraventricular nucleus (PVN) of conscious, chronically instrumented rats? What is the main finding and its importance? Microinjection of vasopressin into the PVN increased mean arterial pressure, heart rate and renal sympathetic nerve activity, all of which were inhibited by pre-injection of the PVN with the V1b antagonist, nelivaptan. The administered vasopressin did not enter the peripheral circulation or increase plasma vasopressin. Ganglionic blockade prevented each of the responses, consistent with mediation by enhanced sympathetic output rather than an increase in circulating vasopressin. Vasopressin (VP) participates in regulation of haemodynamics and volume. Besides more classical actions as a circulating hormone, VP may act via release from axons and dendrites within the CNS. The paraventricular nucleus (PVN) possesses vasopressinergic neurons and a dense complement of VP receptors, including the V1b receptor, which has been implicated in several types of stress responses. We tested the hypothesis that antagonism of V1b receptors will prevent VP-induced increases in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA). Studies were performed in conscious male Sprague-Dawley rats chronically instrumented with vascular catheters, renal nerve electrodes and a cannula stereotaxically directed into the PVN. Unilateral microinjection of VP into the PVN significantly increased MAP, HR and RSNA, peaking at 10 min. Pre-injection of the PVN with the selective V1b receptor antagonist, nelivaptan, did not alter baseline values but blocked the responses to VP. Ganglionic blockade with chlorisondamine decreased MAP and HR and abolished their increase in response to subsequent PVN application of VP. Injection of VP into the PVN did not alter plasma VP levels. Paraventricular nucleus injection with radiolabelled VP resulted in negligible radiolabelled VP in peripheral blood. These findings support the concept that, in basal conditions, PVN V1b receptor activation (rather than VP release into the periphery) may be implicated in the increases in MAP, HR and RSNA due to increased sympathetic outflow. While the role of V1a and oxytocin receptors cannot be excluded, these data suggest that further studies of the role of V1b receptor activation by endogenous VP during stress to effect neuroexcitation are warranted.
Authors: Daniella Thorsdottir; Nicholas C Cruickshank; Zachary Einwag; Grant W Hennig; Benedek Erdos Journal: Am J Physiol Heart Circ Physiol Date: 2019-10-11 Impact factor: 4.733
Authors: Chris L Schaich; Theresa L Wellman; Zachary Einwag; Richard A Dutko; Benedek Erdos Journal: J Neurophysiol Date: 2018-04-25 Impact factor: 2.714