Centrally Induced Hypotension and Bradycardia After Administration of Α‐methylnoradrenaline Into the Area of the Nucleus Tractus Solitarii of the Rat

Jong, W. De; Nijkamp, Frans P.

doi:10.1111/j.1476-5381.1976.tb08628.x

Cited by 92 publications

(19 citation statements)

References 20 publications

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“…Three decades ago it became apparent that A2 neurons may be important for blood pressure regulation and could be a key link in the mechanisms of action of central anti-hypertensive drugs, such as clonidine and α-methylnoradrenaline [6][7][8][9]. Several studies reported that in normotensive rats localised ablation of the NTS by electrolytic lesioning produced fulminating hypertension [10][11][12].…”

Section: Introductionmentioning

confidence: 98%

Restraining influence of A2 neurons in chronic control of arterial pressure in spontaneously hypertensive rats

Duale

Waki

Howorth

et al. 2007

Cardiovascular Research

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Section: Introductionmentioning

confidence: 98%

Restraining influence of A2 neurons in chronic control of arterial pressure in spontaneously hypertensive rats

Duale

Waki

Howorth

et al. 2007

Cardiovascular Research

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“…The NTS is the site of the hypotensive action of ␣-methyl-norepinephrine (␣-MNA), the active metabolite of ␣-methyl-dopa, which is a catecholamine, full agonist at ␣ 2 -adrenoceptors. 10,11 The RVLM/NRL is the major site of the hypotensive effect of imidazoline drugs such as clonidine and rilmenidine, which requires specific imidazoline receptors, insensitive to catecholamines. [12][13][14][15][16][17] Ma et al 18 showed that N G -nitro-L-arginine methyl ester, an NOS inhibitor applied directly into the NTS, inhibited the electrical activity of the cardiovascular neurons.…”

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confidence: 99%

Nitric Oxide and Central Antihypertensive Drugs

Bruban

Bousquet

et al. 2001

Hypertension

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Abstract-NO is known to be involved in the peripheral and central regulation of the cardiovascular function. It plays a neuromodulatory role via a direct action on presynaptic nerve terminals, stimulating the release of ␥-aminobutyric acid, glutamate, and norepinephrine. Our aim was to study the possible role of NO in the cardiovascular effects of the central antihypertensive drugs clonidine, rilmenidine, and ␣-methyl-norepinephrine (␣-MNA). Sites and mechanisms of the hypotensive action of these drugs were different; clonidine and rilmenidine acted on imidazoline receptors in the nucleus reticularis lateralis, whereas ␣-MNA acted upon ␣ 2 -adrenoceptors in the nucleus tractus solitarius. The influence of N G -nitro-L-arginine, an NO synthase inhibitor, on the central hypotensive effects of these drugs was investigated in pentobarbital-anesthetized rabbits. The intracisternal (IC) administration of ␣-MNA (30 g/kg) induced hypotension (79Ϯ2 versus 103Ϯ4 mm Hg) and bradycardia (222Ϯ8 versus 278Ϯ4 bpm) (PϽ0.05) (nϭ5). Clonidine (0.07 g/kg IC) also induced hypotension (69Ϯ5 versus 99Ϯ4 mm Hg) and bradycardia (266Ϯ7 versus 306Ϯ10 bpm) (PϽ0.05) (nϭ5). In addition to clonidine, rilmenidine (1 g/kg IC) induced hypotension (64Ϯ4 versus 97Ϯ4 mm Hg) and bradycardia (264Ϯ11 versus 310Ϯ4 bpm) (PϽ0.05) (nϭ5). Pretreatment with N G -nitro-L-arginine (900 g/kg IC) completely prevented the hypotensive effect of ␣-MNA but influenced the cardiovascular effects of neither clonidine nor rilmenidine. These results confirm that imidazoline drugs, such as clonidine, rilmenidine, and the catecholamine Key Words: nitric oxide Ⅲ blood pressure Ⅲ clonidine Ⅲ norepinephrine Ⅲ central nervous system T he free radical NO is known to be involved in the central and peripheral regulation of the cardiovascular function (for a review, see Krukoff 1 ). In the central nervous system, NO has a neuromodulatory role, influencing the peripheral autonomic function. 2,3 In neurons, the synthesis of NO from L-arginine is catalyzed by the NO synthase enzyme (nNOS), which is calcium/calmodulin dependent. This enzyme is stimulated by glutamate-induced activation of N-methyl-Daspartate receptors, which increases the intracellular influx of calcium; in turn, the diffusible NO activates soluble guanylyl cyclase, producing cGMP in neighboring neurons and astrocytes to trigger its effect. 1,4 Immunohistochemical studies have shown the existence of cellular groups containing nNOS that are constitutive of many important autonomic structures of the hypothalamus, brain stem, and spinal cord. [5][6][7][8][9] We are particularly interested in the brain stem structures of the baroreflex arch, including the nucleus tractus solitarius (NTS) and the rostroventrolateral medulla/nucleus reticularis lateralis (RVLM/NRL). The NTS is the site of the hypotensive action of ␣-methyl-norepinephrine (␣-MNA), the active metabolite of ␣-methyl-dopa, which is a catecholamine, full agonist at ␣ 2 -adrenoceptors. 10,11 The RVLM/NRL is the major site of the hypotensive effect of imidazoli...

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“…6,20,21 This hypothesis is corroborated by the hypotension and bradycardia caused by direct microinjections of NA in the NTS. 37,38 In addition to the alterations observed in the NTS, the transient alteration of TH protein presence within the VLM neuropil might also contribute to the lowered arterial blood pressure observed in adult TG. Indeed, the activity of VLM catecholaminergic neurons is tightly linked to the sympathetic nerve activity and baroreflex sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Delayed Maturation of Catecholamine Phenotype in Nucleus Tractus Solitarius of Rats With Glial Angiotensinogen Depletion

et al. 2003

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Abstract-Cerebral catecholamines and angiotensins are both involved in the regulation of cardiovascular function. Recent in vitro studies have suggested that angiotensin II modulates noradrenergic neurotransmission by controlling both the expression and neuritic trafficking of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. To assess the potential existence of such mechanisms in vivo, we compared TH phenotype ontogeny in the nucleus tractus solitarius (NTS), which is the first central relay of the baroreflex, between control Sprague-Dawley rats and TGR(ASrAOGEN) rats (TG) with glial specific angiotensinogen (AOGEN) depletion. TG displayed a delayed increase in both TH-mRNA and TH protein levels, which sharply rises in the NTS of control rats within the fourth week. The delayed maturation of TH phenotype also affected the presence of TH protein in the neuropil, not only within the NTS region but also within the ventrolateral medulla. This was evidenced by a large decrease in the density of TH-containing neuronal processes in TG at 4 weeks only, without noticeable modification of the labeling of the neuritic marker MAP2, suggesting that neuritic trafficking of TH protein was transiently altered. These results indicate that glial AOGEN is crucial to coordinate within the fourth week the mechanisms driving the maturation of NTS catecholaminergic neurons and suggest that impairment of the central angiotensinergic system early in development can lead to cardiovascular dysfunction related to altered maturation of catecholaminergic neurons located in both the dorsal and the ventrolateral medulla. Key Words: rats, transgenic Ⅲ angiotensin Ⅲ angiotensinogen Ⅲ catecholamines Ⅲ gene expression C atecholamine neurons of Nucleus Tractus Solitarius (NTS), which is the first central relay of the baroreflex, 1 and cerebral angiotensins, in particular angiotensin II (Ang II), play an important role in the regulation of blood pressure. [2][3][4][5][6] This effect of Ang II involves its interaction with NTS neurons through angiotensin type 1 (AT1) receptor. [7][8][9][10] Within this structure, catecholamine (noradrenergic and adrenergic) neurons might be those targeted by Ang II, since (1) they express AT1 receptors at their cell body surface, 11,12 and (2) recent in vitro studies have revealed that Ang II operates chronotropic actions on noradrenergic hypothalamus and brain stem neuronal cocultures from newborn rats. 13 In addition, Ang II has been shown to modulate at longer term the noradrenergic metabolism of these cultured neurons through unusual molecular mechanisms. Indeed, in these neurons, Ang II, through AT1 receptors, not only stimulates the expression of tyrosine hydroxylase (TH), 14,15 the ratelimiting enzyme in catecholamine biosynthesis, 16 but also controls the neuritic trafficking of TH protein. 17 However, such potential modulations of TH phenotype by Ang II have only been characterized in vitro and deserve to be verified in vivo within the NTS.Cerebral angiotensins can be produc...

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Centrally Induced Hypotension and Bradycardia After Administration of Α‐methylnoradrenaline Into the Area of the Nucleus Tractus Solitarii of the Rat

Cited by 92 publications

References 20 publications

Restraining influence of A2 neurons in chronic control of arterial pressure in spontaneously hypertensive rats

Restraining influence of A2 neurons in chronic control of arterial pressure in spontaneously hypertensive rats

Nitric Oxide and Central Antihypertensive Drugs

Delayed Maturation of Catecholamine Phenotype in Nucleus Tractus Solitarius of Rats With Glial Angiotensinogen Depletion

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