Modulation of the baroreceptor reflex by the dorsomedial hypothalamic nucleus and perifornical area

Abstract

(PeF), which lie within the classic hypothalamic defense area, subserve the cardiovascular response to psychological stress. Previous studies have shown that electrical stimulation of the hypothalamic defense area causes inhibition of the cardiac and (in some cases) sympathetic components of the baroreceptor reflex. In contrast, naturally evoked psychological stress does not appear to be associated with such inhibition. In this study, we tested the effect of specific activation of neurons within the DMH and PeF on the baroreflex control of renal sympathetic nerve activity and heart rate in urethane-anesthetized rats. Microinjection of bicuculline (a GABAA receptor antagonist) into the DMH caused dose-dependent increases in heart rate and renal sympathetic activity, shifted the baroreflex control of both variables to higher levels (i.e., increased the upper and lower plateaus of the baroreflex function curves, and increased the threshold, midpoint, and saturation levels of mean arterial pressure). The maximum gain of the sympathetic component of the baroreflex was also increased, while that of the cardiac component was not significantly changed. Increases in the midpoint were very similar in magnitude to the evoked increases in baseline mean arterial pressure. Microinjection of bicuculline into the PeF evoked very similar effects. The results indicate that disinhibition of neurons in the DMH/PeF region not only increases sympathetic vasomotor activity and heart rate but also resets the baroreceptor reflex such that it remains effective, without any decrease in sensitivity, over a higher operating range of arterial pressure. baroreflex resetting; arterial pressure; renal sympathetic nerve activity; heart rate; stress ACUTE PSYCHOLOGICAL STRESS is known to evoke an integrated pattern of behavioral, neuroendocrine, and autonomic responses. For example, air-jet stress results in an increase in arterial blood pressure and heart rate (HR), together with anxiety-like behavior and increased secretion of ACTH (7,20,23,26,27). A substantial body of evidence indicates that the dorsomedial hypothalamic nucleus (DMH) plays a critical role in mediating these responses. In particular, inhibition of the DMH has been shown to greatly reduce the pressor response and tachycardia, as well as the increase in ACTH secretion and anxiety-like behavior, normally evoked by acute psychological stress (14,17,23,26,27) in conscious rats. Furthermore, acute psychological stress has also been shown to increase the level of c-fos expression in the DMH (1, 14, 28).The DMH, as well as the perifornical area (PeF), located more laterally, is part of the classical "hypothalamic defense area" (30), which was so named because stimulation of this region evokes a pattern of autonomic and behavioral changes that are typically observed when an animal is confronted with a threatening stimulus (for reviews see Refs. 5 and 9). The cardiovascular changes include increases in arterial pressure, HR, renal sympathetic nerve activity (RSNA), and skeletal muscle ...

Induction of Fos-immunoreactivity in the rat brain following disinhibition of the dorsomedial hypothalamus

“…Microinjection of BMI into the DMH has been employed in numerous studies in order to disinhibit neurons in the region (Horiuchi et al, 2004(Horiuchi et al, , 2005Da Silva et al, 2006;McDowall et al, 2006;Nakamura and Morrison, 2007), but this study represents the first in which direct evidence for neuronal activation resulting from this disinhibition has been presented. In contrast to a previous report that employed electrical stimulation and relatively high doses of kainate for study (Silveira et al, 1995), we found that the extent of the area of uniformly increased Fos expression emanating from the site of microinjection in the DMH could be delineated with reasonable clarity.…”

“…Neurons in the DMH project to the NTS primarily ipsilaterally (ter Horst and Luiten, 1986;Thompson et al, 1996), and disinhibition of the DMH results in resetting of the baroreflex to a higher level (McDowall et al, 2006), an effect also seen in stress in rats (Hatton et al, 1997, Kanbar et al, 2007. Hypothalamic effects on baroreflex function seem to be exerted, at least in part, at the level of the NTS (Kunos and Vargas, 1995;Chen et al, 1996;Sevoz-Couche et al, 2003) and were historically described as inhibitory (see Nosaka, 1996).…”

Neural Pathways Underlying Lactate-Induced Panic

“…In order for the sympathetic limb of the autonomic nervous system to simultaneously induce hypertension and tachycardia, the baroreflex mechanism which stimulates vagal parasympathetic output and inhibits the sympathetic output needs to be desensitized (see review (McDowall et al, 2006)). Within the DMM (a region that is critical for the baroreflex (Catelli and Sved, 1988) and contains parasympathetic motor neurons), infusions of lactate increased c-Fos-ir cells in the nTS but only in L-AG-treated rats.…”

“…However, increased c-Fos responses in the DMM were not occurring in parasympathetic preganglionic acetylcholinergic neurons (DMV and Amb), or other regions involved in the baroreflex-mediated sympathetic inhibition (eg CVLM) (Chan and Sawchenko, 1998). The DMH directly innervates the nTS (Fontes et al, 2001), and electrical or chemical (see review (McDowall et al, 2006)) stimulation of the DMH decreases the sensitivity of the baroreflex through a GABAergic mechanism in the nTS/DMV (Jordan et al, 1988). This circuit represents an adaptive means of inhibiting the baroreflex during 'fight or flight' responses and exercise (Potts et al, 2003).…”

“…Since evidence from previous studies suggested that disinhibiting the DMH elicits cardioexcitatory responses by mobilizing sympathetic outflow (see review (DiMicco et al, 2002)) and resetting the sensitivity of the baroreflex, which is parasympathetically mediated (see review McDowall et al, 2006), we hypothesized that disinhibition of the DMH/PeF alters lactate-induced behavioral, respiratory, and cardiovascular responses through efferent targets involved in central sympathetic and parasympathetic autonomic control (Dampney, 1994;Thompson and Swanson, 1998;Fontes et al, 2001).…”