Effects of methyldopa metabolites on amine transmitters and adrenergic receptors in rat brain.

Louis, William J.; Conway, Elizabeth L; Summers, Roger J.; Beart, Philip M; Jarrott, Bevyn

doi:10.1161/01.hyp.6.5_pt_2.ii40

Cited by 7 publications

(2 citation statements)

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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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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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confidence: 99%

Nitric Oxide and Central Antihypertensive Drugs

Bruban

Bousquet

et al. 2001

Hypertension

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“…The brain stem structures of the baroreflex arch include the nucleus tractus solitarii and the nucleus reticularis lateralis of the rostral ventrolateral medulla (NRL/RVLM). The nucleus tractus solitarii is a major source of afferent inputs to the NRL/RVLM [4,5], and the site of action of a 2 -ARs ligands such as a-methyl-noradrenaline, a catecholamine selective for a 2 -ARs [6,7]. The NRL/RVLM is an important integrative center of sympathetic control that plays a crucial role in the tonic and phasic regulation of arterial BP [8].…”

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confidence: 99%