The acute hemodynamic effects of α-methyldopa in man

Wilson, William R.; Fisher, F. David; Kirkendall, Walter M.

doi:10.1016/0021-9681(62)90059-0

Cited by 25 publications

(4 citation statements)

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“…Most short-term studies on the effect of orally given a-methyldopa have shown a reduction in BP due to a reduction in total peripheral resistance, with no or only small changes in the cardiac output (CO) (1,10,11,13). In some acute studies clear reductions in CO have been found (8,10,12,14) but the drop in MAP has sometimes been relatively greater and, consequently, there has been a fall in the total peripheral resistance (8,10).…”

Section: Discussionsupporting

confidence: 89%

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Hemodynamic Changes in Long‐term Α‐methyldopa Therapy of Essential Hypertension

Lund‐Johansen

1972

Journal of Internal Medicine

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Thirteen men with untreated essential hypertension in WHO stage I, all working, have been studied ambulatorily. Oxygen consumption, heart rate, cardiac output (Cardiogreen) and intra‐arterial brachial pressure were recorded at rest in supine and sitting position and during steady state work at 300, 600 and 900 kpm/min. The subjects were treated with α‐methyldopa as the sole drug for one year and the hemodynamic study was repeated. The reduction in the intra‐arterial pressure was usually due to a decrease in the cardiac output, with little effect on the calculated total peripheral resistance. The pressure reduction was greatest at rest and during light work. During submaximal exercise the differences between the hemodynamic parameters before and after therapy were small.

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Section: Discussionsupporting

confidence: 89%

“…Before this treatment can be generally accepted, more information about the long-term hemodynamic effect of a-methyldopa would seem relevant. There are several studies on the hemodynamic effect of short-term therapy with this drug (1, 6, 7, 8, 10,11,12,13,14).…”

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confidence: 99%

Hemodynamic Changes in Long‐term Α‐methyldopa Therapy of Essential Hypertension

Lund‐Johansen

1972

Journal of Internal Medicine

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“…Rokseth et al (1962) studied 22 patients before 534 GUANETHIDINE AND METHYLDOPA: A HIEMOD YNAMIC STUDY and after guanethidine, all except one of whom had pulmonary but not systemic hypertension; the drug was administered intravenously and the observations were made in the supine position. Wilson et al (1962) measured the cardiac output in five patients before and after intravenous methyldopa, and again the observations were made in the supine position. These results are, therefore, not necessarily relevant to the everyday treatment of hypertension.…”

Section: Discussionmentioning

confidence: 99%

GUANETHIDINE AND METHYLDOPA: A HAeMODYNAMIC STUDY

Chamberlain¹,

Howard²

1964

Heart

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Guanethidine and methyldopa are commonly used drugs in the treatment of hypertension, but the manner in which they act on the circulation to lower the blood pressure remains controversial. Systemic arterial pressure depends on both cardiac output and total peripheral resistance, and a reduction in either of these can result in a fall of pressure. Guanethidine has been said by some to act principally by lowering peripheral resistance (Lichtlen, Schaub, and Biihlmann, 1960;Roy, Mathur, and Bhatia, 1961;Taylor et al., 1962), while others have considered a fall in cardiac output to be the most important factor (Richardson et al., 1960;Rokseth et al., 1962). Dollery, EmslieSmith, and Shillingford (1961) thought the postural hypotensive effect was to some extent due to a failure of vasoconstriction to compensate for the normal reduction in cardiac output on standing.There is a similar lack of agreement about the action of methyldopa. Sannerstedt, Varnauskas, and Werko (1962) reported a dominant action on peripheral resistance, whereas Wilson, Fisher, and Kirkendall (1962) noted a fall in cardiac output with no significant change in peripheral resistance. Onesti et al. (1962) and Dollery, Harington, and Hodge (1963) found a reduction in both peripheral resistance and cardiac output in most of the patients they studied.There are several reasons for the apparent disparity in the results obtained by different workers. First, in some series, observations were made with subjects supine, and are of limited value in investigating the action of drugs that produce their greatest effect with patients in the upright position. Secondly, most hiemodynamic studies were of the acute effects of the drugs given intravenously: their pharmacology is complicated, and the results may not be comparable to those obtained in investigations of the long-term action of orally administered drugs. Thirdly, the response of patients in heart failure to hypotensive agents is peculiar in that a fall in atrial filling pressure resulting from venous pooling may increase cardiac output (Freis et al., 1953): data obtained from a study of patients with raised venous pressure are therefore not applicable to those in whom it is normal. Finally, there is almost certainly more than one mechanism by which guanethidine and methyldopa reduce blood pressure, and the pattern of response may vary from patient to patient.In this paper, we report the effects on blood pressure, heart rate, and cardiac output of routine treatment of hypertensive patients with oral guanethidine and methyldopa. We have made our observations with the patients supine, propped upright, and walking, both before treatment and after stabilization. We have, therefore, collected our data under conditions that are as relevant as possible to the normal management of hypertension. PATIENTS AND METHODSFifteen patients with a diagnosis of essential hypertension (9 men and 6 women, whose ages ranged from 36 to 71 years) agreed to take part in this study. None had any history of frank heart failure, al...

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“…Generally, when methyldopa is slowly infused over a 30-to 60-minute period, arterial pressure is reduced within 3 hours, and heart rate is unchanged or occasionally decreased. 17 " 19 One potential cardiovascular adverse reaction associated with intravenous methyldopa is a "paradoxical" pressor response. 2021 Although this side effect can be minimized by employing a slow infusion rate, animal 22 and human 20 studies have demonstrated that this side effect is potentially lethal.…”

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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The acute hemodynamic effects of α-methyldopa in man

Cited by 25 publications

References 7 publications

Hemodynamic Changes in Long‐term Α‐methyldopa Therapy of Essential Hypertension

Hemodynamic Changes in Long‐term Α‐methyldopa Therapy of Essential Hypertension

GUANETHIDINE AND METHYLDOPA: A HAeMODYNAMIC STUDY

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

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