α-Methylnoradrenaline induced hypotension and bradycardia after administration into the area of the nucleus tractus solitarii

Nijkamp, Frans P.; Jong, W. De

doi:10.1016/0014-2999(75)90305-2

Cited by 27 publications

(6 citation statements)

References 8 publications

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“…This contention is supported by the findings of others obtained in anesthetized animals that reflex bradycardia produced by elevation of arterial pressure is facilitated by the intracisternal administration of clonidine, an a-adrenergic agonist, 34 ' 35 that norepinephrine injected directly into NTS acutely and transiently lowers blood pressure and HR (an effect, blocked by a-adrenergic antagonists), 7 and that the depressor effects of a-methylnorepinephrine is mediated, in part, through a-adrenergic receptors within the NTS itself. 36 Although we failed to obtain chronic changes in HR following microinjection of 6-OHDA into the NTS, others have noted that the injection of norepinephrine directly into NTS produces bradycardia. 7 Since we have not directly injected norepinephrine into the NTS, we can only speculate as to the reasons for the discrepancy between our results and those of others.…”

Section: Discussionmentioning

confidence: 65%

Chronic lability of arterial pressure produced by selective destruction of the catecholamine innervation of the nucleus tractus solitarii in the rat.

Snyder¹,

Nathan²,

Reis³

1978

Circulation Research

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The effects of selective destruction of the catecholamine innervation of the nucleus tractus solitarii (NTS) on arterial pressure (MAP) and heart rate (HR) were examined in unanesthetized rats in which 6-hydroxydopamine (6-OHDA), 1 ;J, was injected bilaterally into the nucleus at the level of the obex. Control rats received 1 fil of vehicle or were uninjected. Baroreceptor reflex activity was tested by measuring the reflex bradycardia in response to graded doses of phenylephrine. 6-OHDA, 2 /ig, did not alter MAP or HR; 12 /ig, a dose producing necrosis of NTS, resulted in the development within 4-6 hours of fulminating arterial hypertension and tachycardia. 6-OHDA, 4 fig, produced an elevation of MAP which returned to control levels by 48 hours without changing HR. By 6 hours, however, the arterial pressure became extremely labile. Lability of MAP in the absence of hypertension or change of HR persisted for the longest period of observation, 2 weeks. Baroreceptor reflex activity remained, although the sensitivity of the reflex was depressed. 6-OHDA, 4 /ig, failed to produce histological damage to NTS. Biochemically, it resulted after 14 days in a reduction of the activity of dopamine /3-hydroxylase, a specific marker of noradrenergic and adrenergic neurons, to 40% of control without altering the activity of choline acetyltransferase, a marker of cholinergic neurons. We conclude that selective removal of a substantial portion of the catecholamine innervation of the NTS, mostly noradrenergic, results in persistent lability without elevation of arterial pressure. The results suggest that the catecholamine innervation of NTS modulates rather than mediates baroreceptor reflexes, serving to maintain arterial pressure within narrow limits.

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Section: Discussionmentioning

confidence: 65%

Chronic lability of arterial pressure produced by selective destruction of the catecholamine innervation of the nucleus tractus solitarii in the rat.

Snyder¹,

Nathan²,

Reis³

1978

Circulation Research

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“…This nucleus, which receives the major part of the afferent sino-aortic baroreceptor fibres (see Palkovits and Zfiborszky, 1977), is densely innervated by catecholaminergic terminals and contains catecholaminergic cell bodies (DahlstrSm and Fuxe, 1964;Fuxe, 1965;Palkovits and Jacobowitz, 1974). Previous studies showed that local bilateral application of adrenaline, noradrenaline and a-methylnoradrenaline in the NTS caused a decrease of blood pressure and heart rate (De Jong, 1974;Nijkamp and De Jong, 1975;De Jong and Nijkamp, 1976). The A2-region (described by DahlstrSm and Fuxe 1964) was the part of the NTS in which injections of a-methylnoradrenaline were found to be most effective (Zandberg and De Jong, 1977a).…”

Section: Introductionmentioning

confidence: 99%

Effect of catecholamine-receptor stimulating agents on blood pressure after local application in the nucleus tractus solitarii of the medulla oblongata

Zandberg

Jong

Wied

1979

European Journal of Pharmacology

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160

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Effect of catecholamine-receptor stimulating agents on blood pressure after local application in the nucleus tractus solitarii of the medulla oblongata, European J. Pharmacol. 55 (1979) 43--56.The effect of various catecholamines and a-mimetics, given by microinjection in the A2-region of the nucleus tractus solitarii (NTS), on blood pressure was investigated in anesthetized male rats. A dose-dependent decrease of blood pressure and heart rate was induced by adrenaline as the most effective drug, followed by noradrenaline, dopamine, a-methylnoradrenaline and octopamine. Ablation of the rostral or caudal part of the NTS, or removal of the area postrema did not diminish the effect of a-methylnoradrenaline. Higher doses of noradrenaline and a-methylnoradrenaline caused an initial rise of blood pressure, while the blood pressure lowering effect of noradrenaline was diminished, and that of a-methylnoradrenaline and dopamine delayed. Isoprenaline and the (+)-stereoisomers of noradrenaline and a-methylnoradrenaline were ineffective. The hypotensive effect of dopamine was not prevented by systemic injection of the dopamine ~-hydroxylase inhibitor FLA 63. Prior application of haloperidol, yohimbine and phentolamine antagonized the hypotensive response to dopamine and a-methylnoradrenaline. Application of peripherally effective a-mimetics into the A2-region had no or little effect, while high doses increased blood pressure. Tyramine and clonidine caused some decrease of blood pressure. Clonidine also decreased blood pressure when it was applied in the area of the locus coeruleus. Application of isoprenaline in the locus coeruleus also decreased blood pressure while in contrast adrenaline, noradrenaline, dopamine and 0l-methylnoradrenaline increased blood pressure. The present data suggest that the catecholaminergic receptors in the A2-region of the NTS differ from the classic vascular a-receptor and that the NTS also may contain structures which can antagonize the decrease in blood pressure. Catecholamines a-Mimetics Locus coeruleusDecrease of blood pressure Nucleus tractus solitarii

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“…The antihypertensive substance a-methyldopa reduces blood pressure after neuronal uptake and metabolization to amethylnoradrenaline, an c2-adrenoceptor agonist, by a centrally mediated effect on the autonomic nervous system (for review see Henning, 1984). The X2-receptors, that are stimulated by a-methylnoradrenaline, are presumably located in the nucleus tractus solitarii (NTS) (Nijkamp & De Jong, 1975;De Jong & Nijkamp, 1976).…”

Section: Introductionmentioning

confidence: 99%

α‐Methyldopa induces a naltrexone‐insensitive antinociception and hypomotility in rats

Giersberge

Duinkerken

Sweep

et al. 1990

British J Pharmacology

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1. This study served to investigate whether endogenous opioid peptides play a role in the putative antinociceptive and the sedative actions of alpha-methyldopa. 2. In conscious normotensive rats, alpha-methyldopa induced hypotension, starting around 1 h and reaching a maximum 3-4 h after administration. Pretreatment with naltrexone resulted in an inhibition of alpha-methyldopa-induced hypotension. 3. alpha-Methyldopa dose-dependently increased hot plate latency which became evident after a 4 h lag period and reaching a maximum effect at 6 h. The antinociceptive effect of alpha-methyldopa was not affected by naltrexone. 4. In a small open field, alpha-methyldopa dose-dependently suppressed locomotion and sniffing behaviour. These effects of alpha-methyldopa were apparent 1 h after administration and were naltrexone-insensitive. 5. No changes in the level of beta-endorphin-like immunoreactivity in plasma and cerebrospinal fluid were observed after administration of alpha-methyldopa. 6. The results indicate that endogenous opioid peptides are involved in the hypotensive action of alpha-methyldopa but not in alpha-methyldopa-induced hypomotility and antinociception.

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α-Methylnoradrenaline induced hypotension and bradycardia after administration into the area of the nucleus tractus solitarii

Cited by 27 publications

References 8 publications

Chronic lability of arterial pressure produced by selective destruction of the catecholamine innervation of the nucleus tractus solitarii in the rat.

Chronic lability of arterial pressure produced by selective destruction of the catecholamine innervation of the nucleus tractus solitarii in the rat.

Effect of catecholamine-receptor stimulating agents on blood pressure after local application in the nucleus tractus solitarii of the medulla oblongata

α‐Methyldopa induces a naltrexone‐insensitive antinociception and hypomotility in rats

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