Central inhibitory effect of α-methyldopa on blood pressure, heart rate and body temperature of renal hypertensive rats

Nijkamp, Frans P.; Ezer, J.; Jong, W. De

doi:10.1016/0014-2999(75)90046-1

Cited by 28 publications

(5 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…preventing the synthesis of false transmitters peripherally) does not alter the hypotensive effect of methyldopa. On the other hand, this action is abolished after decarboxylase inhibition in both the peripheral and the central nervous system (Henning, 1968(Henning, ,1969aDay, Roach &Whiting, 1973;Nijkamp & de Jong, 1974). Thus central actions of methyldopa amine metabolites mediate the anti-hypertensive effect of the drug.…”

Section: Central Transmitters and Hypertensionmentioning

confidence: 94%

“…Since this effect is counteracted by inhibition of dopamine 8-hydroxylase, a-methylnoradrenaline is probably implicated (Henning & Rubenson, 1971 ;Day et al, 1973), apparently acting by direct stimulation of central noradrenaline receptors (Henning & Rubenson, 1971b;Rubenson, 1971 ;Haeusler & Finch, 1972;Heise & Kroneberg, 1972). These are probably located mainly in the brain stem (Henning & van Zwieten, 1968;Nijkamp & de Jong, 1974).…”

Section: Central Transmitters and Hypertensionmentioning

confidence: 98%

See 1 more Smart Citation

Central Sympathetic Transmitters and Hypertension

Henning

1974

Clinical Science

View full text Add to dashboard Cite

1. The aim of this presentation has been to review the current status of some central neurotransmitter mechanisms in the control of arterial blood pressure and in experimental hypertension. In addition, antihypertensive drugs with centrally mediated actions have been considered.2. There is ample evidence for a role of central noradrenaline mechanisms in central cardiovascular regulation. The catecholamine precursor, ~-3,4-dihydroxyphenylalanine, lowers blood pressure by activating sympatho-inhibitory noradrenergic mechanisms in the lower brain stem. The receptors mediating this effect conform to the a-adrenergic type in peripheral tissues. Central noradrenaline receptors also appear to influence blood pressure at suprabulbar levels in the brain. Evidence is accumulating that central adrenergic receptors of the B type are also implicated in cardiovascular control. Central dopamine, 5-hydroxytryptamine and acetylcholine neurons are possibly involved in circulatory regulation but their precise role is less clear at present.3. Considerable work has been done attempting to relate alterations in central neurotransmitter function to arterial hypertension. Central noradrenaline neurons appear to participate in the origin and maintenance of neurogenic hypertension. This may also be the case for other types of experimental hypertension but the results are less conclusive.4. Anti-hypertensive drugs may act by interfering with central neurotransmitter function. The action of ~-a-methyl-3,4-dihydroxyphenylalanine (methyldopa) is largely mediated through an activation by its metabolite, methylnoradrenaline, of noradrenaline mechanisms in the lower brain stem. The central noradrenaline agonist, clonidine, probably acts in an analogous way although some evidence indicates that this drug may influence blood pressure at several levels of central cardiovascular control.

show abstract

Section: Central Transmitters and Hypertensionmentioning

confidence: 94%

Section: Central Transmitters and Hypertensionmentioning

confidence: 98%

Central Sympathetic Transmitters and Hypertension

Henning

1974

Clinical Science

View full text Add to dashboard Cite

show abstract

“…Blood pressure was continuously recorded from a permanent indwelling iliac cannula (Nijkamp et al, 1975) with a Statham transducer (Model P23-AC) connected to a Grass polygraph. The iliac cannula had been implanted under ether anesthesia at least 24 hr prior to the experiment.…”

Section: Methodsmentioning

confidence: 99%

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

Nijkamp¹,

Jong²

1975

European Journal of Pharmacology

Self Cite

View full text Add to dashboard Cite

, 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.

show abstract

“…is a synthetic neutral AA which exerts a hypotensive effect through a central site of action (Nijkamp et al, 1975, Badoer et al, 1983. The importance of competitive transport in determining brain aMD uptake and levels was illustrated by the effects of changes in diet, which result in alterations in plasma neutral AA levels (Fernstrom, 1979).…”

Section: L-alphamethyldopa ( L~m D )mentioning

confidence: 99%

COMPARATIVE PHARMACOKINETICS OF d‐ AND l‐ALPHAMETHYLDOPA IN PLASMA, AQUEOUS HUMOR, AND CEREBROSPINAL FLUID IN RABBITS

Auclair

Laude

Wainer

et al. 1988

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

The 2 stereoisomers of alphamethyldopa (alpha MD) were separately injected IV at 3 different doses (3, 10, 30 mg/kg) in anesthetized rabbits. Samples of plasma, aqueous humor (AH), and cerebrospinal fluid (CSF) were collected over a 300-min period. The concentration of the aminoacid (AA) was determined by liquid chromatography and electrochemical detection. Parameters obtained from kinetic analyses of the plasma concentrations were close to the values reported in other species. Linear elimination kinetics were observed in the dose range studied. A marked dose-dependent entry of alpha MD was observed in AH. A stereospecific active transport of alpha MD was evidenced in the AH since the concentration of the L-isomer reached values above the plasma levels. CSF entry of the AA was small when compared to AH kinetics. A limited passive diffusion of the AA in the brain could account for this phenomenon. However, greater availability of the L-stereoisomer was still observed in CSF. These alpha MD kinetic analyses illustrate the adaptation of AH and CSF removal procedures to the pharmacokinetic studies of the brain and ocular entry of AA isomers.

show abstract

Central inhibitory effect of α-methyldopa on blood pressure, heart rate and body temperature of renal hypertensive rats

Cited by 28 publications

References 27 publications

Central Sympathetic Transmitters and Hypertension

Central Sympathetic Transmitters and Hypertension

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

COMPARATIVE PHARMACOKINETICS OF d‐ AND l‐ALPHAMETHYLDOPA IN PLASMA, AQUEOUS HUMOR, AND CEREBROSPINAL FLUID IN RABBITS

Contact Info

Product

Resources

About