Baroreflex regulation of renal sympathetic nerve activity and heart rate in renal wrap hypertensive rats

Vitela, Melissa; Herrera-Rosales, Myrna; Haywood, Joseph R.; Mifflin, Steve

doi:10.1152/ajpregu.00620.2004

Cited by 28 publications

(29 citation statements)

References 42 publications

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“…Furthermore, the magnitudes of the maximum and minimum reflex changes in RSNA relative to the RSNA value at the midpoint in our study were also very similar to those in the conscious rat (16). The range of the evoked baroreflex changes in HR in our study, however, as in previous studies in anesthetized rats (24,29), was less than that observed in the conscious rat (16,24,29). Nevertheless, our results do not indicate that disinhibition of DMH or PeF neurons reduces the sensitivity of the cardiac component of the baroreceptor reflex.…”

Section: Discussionsupporting

confidence: 88%

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

McDowall¹,

Horiuchi²,

Killinger³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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(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 ...

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Section: Discussionsupporting

confidence: 88%

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

McDowall¹,

Horiuchi²,

Killinger³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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“…As a result of these two factors, the overall contribution of C-fiber afferents to baroreflex regulation may increase in HT relative to A-fiber inputs. In 4-wk HT rats, the baroreflex curve relating renal sympathetic nerve discharge to MAP is shifted to the right with no change in gain, while the curve relating HR to MAP is shifted to the right with a reduced gain (Vitela et al 2005). The relative role of C-fiber versus A-fiber baroreceptor afferent inputs to specific aspects of reflex function remains to be determined.…”

mentioning

confidence: 97%

Transient Voltage-Dependent Potassium Currents Are Reduced in NTS Neurons Isolated From Renal Wrap Hypertensive Rats

Belugin

Mifflin²

2005

Journal of Neurophysiology

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Belugin, Sergei and Steve Mifflin. Transient voltage-dependent potassium currents are reduced in NTS neurons isolated from renal wrap hypertensive rats. J Neurophysiol 94: 3849 -3859, 2005; doi:10.1152/jn.00573.2005. Whole cell patch-clamp measurements were made in neurons enzymatically dispersed from the nucleus of the solitary tract (NTS) to determine if alterations occur in voltagedependent potassium channels from rats made hypertensive (HT) by unilateral nephrectomy/renal wrap for 4 wk. Some rats had the fluorescent tracer DiA applied to the aortic nerve before the experiment to identify NTS neurons receiving monosynaptic baroreceptor afferent inputs. Mean arterial pressure (MAP) was greater in 4-wk HT (165 Ϯ 5 mmHg, n ϭ 26, P Ͻ 0.001) rats compared with normotensive (NT) rats (109 Ϯ 3 mmHg measured in 10 of 69 rats). Transient outward currents (TOCs) were observed in 67-82% of NTS neurons from NT and HT rats. At activation voltages from Ϫ10 to ϩ10 mV, TOCs were significantly less in HT neurons compared with those observed in NT neurons (P Ͻ 0.001). There were no differences in the voltage-dependent activation kinetics, the voltage dependence of steady-state inactivation, and the rise and decay time constants of the TOCs comparing neurons isolated from NT and HT rats. The 4-aminopyridine-sensitive component of the TOC was significantly less in neurons from HT compared with NT rats (P Ͻ 0.001), whereas steady-state outward currents, whether or not sensitive to 4-aminopyridine or tetraethylammonium, were not different. Delayed excitation, studied under current clamp, was observed in 60 -80% of NTS neurons from NT and HT rats and was not different comparing neurons from NT and HT rats. However, examination of the subset of NTS neurons exhibiting somatic DiA fluorescence revealed that DiA-labeled neurons from HT rats had a significantly shorter duration delayed excitation (n ϭ 8 cells, P ϭ 0.022) than DiA-labeled neurons from NT rats (n ϭ 7 cells). Neurons with delayed excitation from HT rats had a significantly broader first action potential (AP) and a slower maximal downstroke velocity of repolarization compared with NT neurons with delayed excitation (P ϭ 0.016 and P ϭ 0.014, respectively). The number of APs in the first 200 ms of a sustained depolarization was greater in HT than NT neurons (P ϭ 0.012). These results suggest that HT of 4-wk duration reduces TOCs in NTS neurons, and this contributes to reduced delayed excitation and increased AP responses to depolarizing inputs. Such changes could alter baroreflex function in hypertension.

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“…This enhanced postsynaptic baclofen effect could contribute to the enhanced baclofen-induced pressor response observed in chronic hypertension and altered baroreflex function in hypertension. 14 …”

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confidence: 99%

Chronic Hypertension Enhances the Postsynaptic Effect of Baclofen in the Nucleus Tractus Solitarius

2007

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Abstract-Microinjection of the inhibitory neurotransmitter ␥-aminobutyric acid B-subtype receptor agonist baclofen into the nucleus tractus solitarius increases arterial blood pressure and sympathetic nerve discharge. The baclofen-induced pressor response is enhanced in chronic hypertension. We hypothesized that a postsynaptic mechanism contributes to the enhanced responses to baclofen in hypertension. We investigated the postsynaptic effect of baclofen on second-order baroreceptor neurons, identified by 1,1Ј-dilinoleyl-3,3,3Ј,3Ј-tetra-methylindocarbocyanine, 4-chlorobenzenesulphonate labeling of the aortic nerve, in nucleus tractus solitarius slices from sham-operated normotensive and unilateral nephrectomized, renal-wrap hypertensive rats. Key Words: cardiovasular regulation Ⅲ baroreceptor Ⅲ baroreflex Ⅲ hypertension Ⅲ blood pressure T he nucleus tractus solitarius (NTS) is the first site of baroreceptor afferent integration within the central nervous system. 1,2 The synaptic transmission of baroreceptor afferents within the NTS is constantly modulated by both excitatory and inhibitory inputs mediated by many neurotransmitters, including the inhibitory neurotransmitter ␥-aminobutyric acid (GABA). Microinjection of baclofen, a selective GABA B-subtype (GABA B ) receptor agonist, into the NTS results in an increase in arterial pressure, heart rate, and renal sympathetic nerve discharge, 3-5 which are expected, because baclofen inhibits NTS neurons that integrate baroreceptor afferent inputs. 6 -8 This baclofen-induced pressor response is enhanced in several animal models of chronic hypertension, including the spontaneously hypertensive rat, 9,10 deoxycorticosterone salt-hypertensive rats, 11 and 1-kidney, renal wrap models of hypertension. 6 -8,12 Baclofen can presynaptically inhibit glutamate release from afferent terminals and postsynaptically induce outward current to reduce neuronal excitability in the NTS. 13 However, it is not known to what extent postsynaptic GABA B receptor-mediated inhibition contributes to the enhanced baclofen-induced pressor response in chronic hypertension.Previous studies from this laboratory have demonstrated that renal-wrap hypertension is associated with increased GABA B receptor-mediated inhibition of baroreceptor-evoked discharge in NTS neurons 8 and increased expression of GABA B receptor mRNA in the NTS. 7 To clarify GABA B receptor-mediated cellular mechanisms in the neuronal adaptations to chronic hypertension, the present study investigated the postsynaptic effect of baclofen on NTS neurons receiving monosynaptic afferent inputs from baroreceptors and the influence of chronic hypertension on the postsynaptic response to baclofen. We addressed these questions using an in vitro patch-clamp method to directly investigate the postsynaptic effect of baclofen on second-order baroreceptor neurons in the NTS. The results demonstrated that, after chronic hypertension, second-order neurons showed enhanced postsynaptic responses to baclofen. This enhanced postsynaptic baclofen ef...

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Baroreflex regulation of renal sympathetic nerve activity and heart rate in renal wrap hypertensive rats

Cited by 28 publications

References 42 publications

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

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

Transient Voltage-Dependent Potassium Currents Are Reduced in NTS Neurons Isolated From Renal Wrap Hypertensive Rats

Chronic Hypertension Enhances the Postsynaptic Effect of Baclofen in the Nucleus Tractus Solitarius

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