Role of vasopressin in sympathetic response to paraventricular nucleus stimulation in anesthetized rats

Abstract

Vasopressin may play an extrahypothalamic role in the central control of the cardiovascular system, specifically acting as a spinal neurotransmitter in the pathway where the paraventricular nucleus (PVN) alters sympathetic outflow. In this study, the effect of stimulating neuronal cell bodies in the PVN on renal sympathetic nerve activity (RSNA) and the possible involvement of vasopressin in the pathway was investigated in anesthetized rats. The PVN was stimulated by microinjection with 0.2 M D,L-homocysteic acid via a glass micropipette, and the hemodynamic and sympathetic responses were recorded. A computerized sympathetic peak-detection algorithm was applied to recordings of sympathetic discharges to retrieve information about the characteristics of RSNA during PVN stimulation. The algorithm scanned the series of RSNA voltages for significant increases followed by significant decreases in a small cluster of voltage values. Once each synchronized RSNA peak had been detected, its corresponding amplitude and peak-to-peak interval were calculated. PVN stimulation consistently increased the amplitude of RSNA (mean 30 +/- 5.6% over control), arterial pressure, and the peak-to-peak interval of discharges. A V1 vasopressin antagonist intrathecally administered as a 500-pmol dose was subsequently able to completely block the hemodynamic response (blood pressure increase of 14 +/- 5%) and a 35 +/- 6% increase in RSNA in response to PVN stimulation and intrathecal vasopressin. Thus spinal vasopressin is likely to be a neurotransmitter involved in the cardiovascular regulation involving the PVN.

Neuropeptides, Amines and Amino Acids as Mediators of the Sympathetic Effects of Paraventricular Nucleus Activation in the Rat

“…Furthermore we and others have previously shown that a V 1a antagonist given intrathecally blocks PVN-induced excitation of RSNA (Riphagen & Pittman, 1989;Malpas & Coote, 1994) and that sympathetic preganglionic neurones express V 1a receptors (Sermasi et al 1998). In addition vasopressin terminals are closely associated anatomically with these spinal neurones (Motawei et al 1999).…”

“…However, there is mounting evidence that another brain site, the paraventricular nucleus (PVN) of the hypothalamus has a significant influence on vasomotor activity (Coote, 1995;Badoer, 1996). There is good evidence that part of this influence is via a direct spinal projection (Malpas & Coote, 1994) which innervates sympathetic preganglionic neurones in the spinal cord (Ranson et al 1998). This spinal projection consists of separate populations of neurones containing vasopressin, oxytocin, other neuropeptides and dopamine (Sawchenko & Swanson, 1982;Cechetto & Saper, 1988).…”

“…The present experiments were designed to determine if the effects of PVN stimulation could be related to activation of the spinally projecting PVN neuronal phenotypes. For this we used a similar approach to that described previously (Malpas & Coote, 1994). Renal sympathetic nerve activity (RSNA) was recorded whilst stimulating pressor or depressor sites in PVN and the effect on the responses of intrathecal (I.T.)…”

Urocortin 2 induces potent long-lasting inhibition of cardiac sympathetic drive despite baroreflex activation in conscious sheep

“…Sympathetic nerve burst frequency reflects probability of firing of individual fibers, is gated to HR, and is regulated primarily by baroreflex responses to rapid changes in blood pressure (Sundlof & Wallin 1978, Malpas & Ninomiya 1992a). However, burst size, reflecting recruitment of postganglionic fibers, is more affected by central pathways, for example, paraventricular nucleus secretion of vasopressin (Malpas & Coote 1994) and chemoreceptor stimulation (Malpas & Ninomiya 1992b). Therefore, the temporal changes we observed in different CSNA indices may be explained by the immediate indirect effects of baroreflex unloading coupled with more persistent direct sympathoinhibitory effects of UCN2 on the CNS.…”

Cardiovascular/Respiratory Control

“…Lovick Selective stimulation of neurones in the paraventricular nucleus (PVN) of the hypothalamus has been shown to produce changes in sympathetic nerve activity (e.g. Kannan et al 1989;Malpas & Coote, 1994). These changes may be involved in mediating cardiovascular changes in response to altered blood volume (Lovick et al 1993).…”