Further evidence for a central hypotensive action of α‐methyldopa in both the rat and cat

Finch, L.; Haeusler, G.

doi:10.1111/j.1476-5381.1973.tb08319.x

Cited by 94 publications

(31 citation statements)

References 34 publications

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“…Blood pressure in mm Hg Heart rate in bpm blockade by intraventricularly administered phentolamine prevented the fall in blood pressure caused by a-methyldopa (Finch and Hauesler, 1973). In the present study injection of phentolamine into the area of the nucleus tractus solitarii inhibited both the hypotension and bradycardia induced by ~-methylnoradrenaline.…”

Section: Treatmentsupporting

confidence: 56%

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

Nijkamp¹,

Jong²

1975

European Journal of Pharmacology

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, a-Methylnoradrenaline induced hypotension and bradycardia after administration into the area of the nucleus tractus solitarii, European J. Pharmacol. 32 (1975) 361--364.Bilateral injeetions of a-methylnoradrenaline into the area of the nucleus tractus solitarii of the brain stem caused a dose-dependent decrease of systemic arterial blood pressure and heart rate of anesthetized rats. The effects were prevented and even reversed by a preceding injection of the a-adrenoceptor blocking agent phentolamine. Pressor doses of angiotensin II and of arginine-vasopressin at the same site failed to decrease blood pressure and heart rate.

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Section: Treatmentsupporting

confidence: 56%

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

Nijkamp¹,

Jong²

1975

European Journal of Pharmacology

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“…The persistence of the response to PCPAME after destruction of central noradrenergic inhibitory pathways by 6-OHDA, suggests that a false transmitter acting through central noradrenergic inhibitory pathways is unlikely to mediate the hypotensive response to PCPAME in normotensive rats. The same pretreatment regimen has been shown in other studies to produce a widespread destruction of the nerve terminals of central noradrenergic neurones (Uretsky & Iversen, 1970) and to inhibit the antihypertensive response to a-methyldopa in genetically hypertensive rats (Finch & Hauesler, 1973). There remains the possibility that bundles of noradrenergic neurones involved in such a mediated response could be insensitive to this pretreatment regimen of 6-OHDA.…”

Section: Discussionmentioning

confidence: 54%

PROLONGED EFFECTS OF p‐CHLOROPHENYLALANINE ON THE BLOOD PRESSURE OF CONSCIOUS NORMOTENSIVE AND DOCA/SALINE HYPERTENSIVE RATS

Buckingham

Hamilton

Moore

1976

British J Pharmacology

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In deoxycorticosterone acetate (DOCA) saline hypertensive rats a single dose of p‐chlorophenylalanine methylester (PCPAME) (400 mg/kg i.p.) produced a significant fall in blood pressure (20–43 mmHg) which lasted for at least 8 days and was accompanied by a parallel depletion of brain stem 5‐hydroxytryptamine (5‐HT) but not of noradrenaline (NA). In normotensive rats single doses of PCPAME (200 and 400 mg/kg i.p.) produced a significant hypotension (15–20 mmHg) after a latent period of 5 days. An initial pressor response (12 mmHg) was observed at the higher dose level only on day 3. The hypotensive response to PCPAME (200 mg/kg i.p.) in normotensive rats was not modified by pretreatment with 5,6‐dihydroxytryptamine (5,6‐DHT; 50 μg i.c.v.) or 6‐hydroxydopamine (6‐OHDA; 3 × 250 μg intracerebroventricularly). It is concluded that the hypotensive response to PCPAME in normotensive rats is independent of brain stem depletion of 5‐HT and is probably not mediated by the formation of a false transmitter substance acting via central noradrenergic inhibitory pathways. The mechanism involved in the antihypertensive response to PCPAME in DOCA/saline hypertensive rats has yet to be defined.

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“…However, it is apparent that while the antihypertensive response to methyldopa is prevented by drugs that destroy brain catecholaminergic nerve endings, 29 this response is unaffected by drugs that cause depletion of endogenous brain catecholamines. 6 The implication of these findings is that methyldopa, like clonidine, 3 …”

Section: Discussionmentioning

confidence: 99%

Effect of methyldopa on brain cholinergic neurons involved in cardiovascular regulation. A study in conscious spontaneously hypertensive rats.

Buccafusco¹

1984

Hypertension

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SUMMARY Chemical stimulation of brain cholinergic neurons in many species can produce hypertension. Recent studies in this laboratory have demonstrated that clonidine inhibits this central cholinergic pressor response by inhibiting the biosynthesis of brain acetylcholine. This study was designed to determine whether methyldopa, like clonidine, could inhibit brain cholinergic neurons involved in cardiovascular regulation in freely-moving spontaneously hypertensive rats (SHR). Intravenous (i.v.) injection of methyldopa (50-200 mg/kg) produced a dose-related fall in blood pressure (29/15-54/33 mm Hg) in SHR. Intracerebroventricular (i.c.v.) injection of hemicholinium-3 (HC-3) in SHR evoked a fall in arterial pressure through inhibition of acetylcholine synthesis. Doses of HC-3 (10 /ng, or 15 pLf>, i.c.v.) and methyldopa (50 mg/kg, i.v.) were administered to produce small reductions in arterial pressure in SHR (7-14 mm Hg diastolic, respectively). When the two agents were injected simultaneously, however, a greater than additive response was obtained (p < 0.05). Central injection of echothiophate (a long-acting cholinesterase inhibitor) to potentiate brain cholinergic activity resulted in a sustained hypertensive response (>40 mm Hg) in SHR for at least 150 minutes. Simultaneous injection of or pretreatment with methyldopa (100 mg/kg, i.v.) inhibited the pressor response to echothiophate over a time course similar to its antihypertensive response in untreated SHR. Methyldopa, however, was completely ineffective in altering the hypertensive response to central injection of carbachol (1 /xg, i.c.v.). This difference in methyldopa susceptibility between the indirect-acting (echothiophate) and direct-acting (carbachol) cholinergic agonists may be related to an inhibiting effect of methyldopa on brain acetylcholine release. These data support our previous studies with clonidine and suggest a cholinergic component in the antihypertensive action of these drugs. 1 -2 These receptors, however, do not appear to be located either presynaptically or postsynaptically upon central adrenergic neurons, since the antihypertensive effect of clonidine is not affected by drug treatments which cause depletion of brain catecholamines or which destroy adrenergic nerve endings.3 " 3 Likewise the hypotensive action of methyldopa is unaffected following severe depletion of brain catecholamines. 6 Recent studies in this laboratory haveFrom the

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Further evidence for a central hypotensive action of α‐methyldopa in both the rat and cat

Cited by 94 publications

References 34 publications

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

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

PROLONGED EFFECTS OF p‐CHLOROPHENYLALANINE ON THE BLOOD PRESSURE OF CONSCIOUS NORMOTENSIVE AND DOCA/SALINE HYPERTENSIVE RATS

Effect of methyldopa on brain cholinergic neurons involved in cardiovascular regulation. A study in conscious spontaneously hypertensive rats.

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