Effect of Sinoaortic Deafferentation on Renal Wrap Hypertension

VanNess, J. Mark; Hinojosa‐Laborde, Carmen; Craig, Teresa; Haywood, Joseph R.

doi:10.1161/01.hyp.33.1.476

Cited by 16 publications

(14 citation statements)

References 26 publications

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“…A recent report demonstrated that baroreflex function, assessed as a tonic sympathoinhibitory drive, is present in renal wrap HT rats. 25 Adaptations within the NTS such as those described in this report and others 6,24 may play a role in the maintenance of some degree of baroreflex function in the setting of altered baroreceptor afferent input during long-term elevations in blood pressure.…”

Section: Single-unit Recordingsmentioning

confidence: 51%

Integration of Aortic Nerve Inputs in Hypertensive Rats

Zhang

Mifflin

2000

Hypertension

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Abstract-The integration of arterial baroreceptor afferent inputs was studied in renal wrap hypertensive (HT) and normotensive (NT) rats. In anesthetized and paralyzed rats, aortic nerve (AN)-evoked depressor responses were reduced in HT compared with NT rats (PϽ0.05). We tested the hypothesis that the attenuated baroreflex was associated with altered integration of baroreceptor inputs within the nucleus of the solitary tract. Based on onset latency and the ability of monosynaptic neurons (MSNs) to respond to each of 2 AN stimuli separated by 5 ms, cells in HT and NT rats were divided into 3 groups: short-latency MSNs (SLMSNs), long-latency MSNs (LLMSNs), and polysynaptic neurons (PSNs Key Words: reflex Ⅲ electrophysiology Ⅲ hypertension, renal I n human 1,2 and many animal 3-8 models, hypertension is associated with alterations in baroreflex regulatory function. Hypertension-induced changes at the level of the baroreceptor result in, or contribute to, altered reflex function. 9 -11 Numerous studies have also suggested that alterations within various sites within the central nervous system contribute to the changes in reflex function observed in hypertension. 6,8,[12][13][14][15][16][17] The nucleus of the solitary tract (NTS) is the primary site of the termination of baroreceptor afferents within the central nervous system. 18 Despite its pivotal role in central cardiovascular regulation, its function in hypertension has received little attention.The goals of the present study were 2-fold. The first was to determine whether alterations in baroreflex function occur in a 1-kidney, renal wrap model of hypertension, 19 which, in contrast to genetic models such as spontaneously hypertensive rats (SHR) or Dahl rats, is a surgically induced model of hypertension. This was accomplished through electrical stimulation of the aortic nerve (AN), which eliminated altered transduction by the baroreceptor as a contributing factor to any observed alterations. The second goal was to examine the integration of AN-evoked inputs to neurons in the NTS to determine whether there were any discernible alterations in the integration of baroreceptor afferent inputs during their initial processing within the central nervous system. Methods Chronic Hypertensive ModelSuccessful experiments were performed on 179 male SpragueDawley rats (375 to 500 g; Charles River Laboratories or Harlan Sprague-Dawley Inc). Rats were housed 2 per cage in a fully accredited (AAALAC and USDA) laboratory animal room with free access to food and water. All rats were allowed at least 1 week to acclimate before use in any procedures. All experimental protocols were approved by the institutional animal care and use committee.Hypertension was induced in 48 rats through a 1-kidney, renal wrap procedure. 19 Rats were anesthetized with medetomidine (0.5 mg/kg IP; Pfizer) and ketamine (75 mg/kg IP; Fort Dodge Laboratory). A figure-8 Grollman renal wrap and contralateral nephrectomy were performed on the animals. Control animals consisted of sham-operated rats that were...

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Section: Single-unit Recordingsmentioning

confidence: 51%

Integration of Aortic Nerve Inputs in Hypertensive Rats

Zhang

Mifflin

2000

Hypertension

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“…It is appropriate to speculate on the possible triggers that initiate the alterations in sensitivity to GABAergic agonists observed in this study. Enhanced excitatory (7) or inhibitory synaptic input and/or circulating hormones (e.g., angiotensin and catecholamines) (5,6,16) could serve to initiate the alterations. Modulation of GABA A receptor function can be the result of any number of potential mechanisms, including, but not restricted to, regulation of receptor number and/or affinity, regulation of the phosphorylation status of the receptor, and alterations in receptor subunit composition (12).…”

Section: Discussionmentioning

confidence: 99%

Hypertension alters GABA receptor-mediated inhibition of neurons in the nucleus of the solitary tract

Mei

Zhang

Mifflin

2003

American Journal of Physiology-Regulatory, Integrative and Comp

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. Hypertension alters GABA receptor-mediated inhibition of neurons in the nucleus of the solitary tract. Am J Physiol Regul Integr Comp Physiol 285: R1276-R1286, 2003 10.1152/ajpregu. 00255.2003.-Previous studies have demonstrated that microinjection of baclofen, a GABA B receptor agonist, into the nucleus of the solitary tract (NTS) results in an enhanced pressor response in hypertensive (HT) rats compared with normotensive (NT) rats, suggesting a possible alteration in the responses of neurons in this area to activation of GABA B receptors. The following studies were designed to determine whether HT alters the sensitivity of neurons in the NTS to GABA receptor agonists. Sham-operated NT and unilateral nephrectomized, renal-wrap HT Sprague-Dawley rats were anesthetized, and the responses of NTS neurons receiving aortic nerve (AN) afferent inputs to iontophoretic application of GABA, the GABA A receptor agonist muscimol, and the GABA B agonist baclofen were examined. The AN input was classified as monosynaptic (MSN) if the cell responded to each of two stimuli separated by 5 ms with an action potential. If the cell did not respond, the input was considered polysynaptic (PSN). In MSNs, inhibition of AN-evoked discharge by GABA was not altered in 1 wk of HT but was reduced in 4 wk of HT, whereas in PSNs, sensitivity to GABA was reduced at 1 and 4 wk of HT. In HT rats, inhibition of AN-evoked discharge by baclofen was enhanced in MSNs, but not in PSNs, after 1 and 4 wk of HT, whereas inhibition by muscimol was reduced in MSNs and PSNs at 1 and 4 wk of HT. Changes in sensitivity to muscimol and baclofen within MSNs were the same whether the MSN received a slowly or a rapidly conducted AN afferent input. The results demonstrate that early in HT the sensitivity of NTS neurons to inhibitory amino acids is altered and that these changes are maintained for Ն4 wk. The alterations are dependent on the subtype of GABA receptor being activated and whether the neuron receives a mono-or polysynaptic baroreceptor afferent input. (12), and GABA B receptors are metabotropic, G protein-coupled receptors that mediate presynaptic and postsynaptic inhibition by reductions in calcium conductance or increases in potassium conductance, respectively (8). Activation of GABA A receptors on NTS neurons results in chloride-dependent membrane hyperpolarization and inhibition of baroreceptor-evoked discharge (10,19). Activation of GABA B receptors can evoke presynaptic and/or postsynaptic inhibition of NTS neurons (1, 19) and inhibit baroreceptor-evoked discharge in NTS neurons (19).The sensitivity of NTS neurons to the selective GABA A agonist muscimol was the same whether the neuron received a monosynaptic or a polysynaptic aortic nerve (AN) input (19). In contrast, NTS neurons receiving a monosynaptic AN input were much less sensitive to the inhibitory effects of the GABA B agonist baclofen than were NTS neurons receiving a polysynaptic AN input (19). An in vitro study reported that presynaptic inhibition of monosynaptic tractus inputs t...

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“…This observation of a recovery in arterial pressure in the SAD animals with nitric oxide inhibition is very different from arterial pressure changes during other interventions in which chronic changes in mean arterial pressure are found to be similar in SAD and intact animals. 15,16 SAD animals did not have a sustained increase in arterial pressure with nitric oxide blockade, suggesting that the baroreflex is exerting a chronic effect over arterial pressure. This action may occur through a chronic modulation of the mean level of SNA.…”

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confidence: 94%

Chronic Blockade of Nitric Oxide Does Not Produce Hypertension in Baroreceptor Denervated Rabbits

2003

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Abstract-Although the vascular action of endothelium-derived nitric oxide in modulating arterial pressure is well established, nitric oxide can also act as a neurotransmitter in the central nervous system. In addition, there is evidence for an interaction between nitric oxide and baroreceptor afferent processing; thus, nitric oxide may regulate blood pressure through central modulation of arterial baroreflexes. To test this possible interaction of nitric oxide and baroreflexes in the long-term regulation of blood pressure, we measured arterial pressure and heart rate responses to nitric oxide blockade by using L-NAME (50 mg/kg per day in drinking water) over 7 days in baroreceptor intact and sinoaortic denervated conscious rabbits. In the baroreceptor intact animals, blockade of nitric oxide leads to a significant increase in mean arterial pressure (from 75Ϯ2 to 84Ϯ3 mm Hg) and decrease in heart rate (from 233Ϯ8 to 195Ϯ8 bpm) that was sustained over the 7 days of nitric oxide blockade. In the sinoaortic denervated animals, blockade of nitric oxide initially led to a similar increase in arterial pressure (82Ϯ3 mm Hg on the second day), but in all sinoaortic denervated animals this increase was not sustained and recovered back to pre-L-NAME levels. This finding indicates that baroreflexes play an important role in the long-term control of blood pressure, and, second, that one mediator of this control is nitric oxide. Key Words: baroreflex Ⅲ sympathetic nervous system Ⅲ blood pressure Ⅲ hypertension, chronic Ⅲ nitric oxide A lthough the vascular actions of endothelium-derived nitric oxide in modulating arterial pressure are well established, 1,2 nitric oxide can also act as a neurotransmitter in the central nervous system. Acute studies indicate a central action of nitric oxide on sympathetic nerve activity, 3 but the role of nitric oxide in regulating long-term control of arterial pressure through a chronic action on sympathetic nerve activity has not been widely considered. The action of nitric oxide on arterial pressure through arterial baroreflexes has been considered irrelevant because baroreflexes were considered to reset with sustained increases in blood pressure. 4,5 However, recent research indicates that baroreflexes may indeed play a role in the long-term regulation of blood pressure. Thrasher 6 developed a new surgical method to produce chronic unloading of arterial baroreceptors in dogs in which the aortic baroreceptor nerves were cut and the carotid sinus was isolated from the systemic arterial pressure. Baroreceptor unloading was induced by ligation of the common carotid artery proximal to the innervated sinus. Arterial pressure was consequently increased an average of 22 mm Hg above control. Given that nitric oxide has been shown to modulate baroreceptor afferent processing at the level of the nucleus tractus solitarius 7 and recent work by Thrasher, 6 it follows that an important chronic action of nitric oxide on arterial pressure may be through modulation of arterial baroreflexes. To test this pos...

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Effect of Sinoaortic Deafferentation on Renal Wrap Hypertension

Cited by 16 publications

References 26 publications

Integration of Aortic Nerve Inputs in Hypertensive Rats

Integration of Aortic Nerve Inputs in Hypertensive Rats

Hypertension alters GABA receptor-mediated inhibition of neurons in the nucleus of the solitary tract

Chronic Blockade of Nitric Oxide Does Not Produce Hypertension in Baroreceptor Denervated Rabbits

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