The Acute Hemodynamic Effects of L-Alpha Methyldopa

Vincent, William A.; Kashemsant, Udomporn; Cuddy, Richard P.; Smulyan, Harold; Eich, Robert H.

doi:10.1097/00000441-196311000-00006

Cited by 15 publications

(5 citation statements)

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“…Inspection of Figure 3 reveals that the combined treatment was responsible for these differences. There was also a significant interactive component for the two groups of curves, F = 3.58 (18,171), p < 0.01 and F = 4.34 (18,126), p < 0.01, respectively. This interactive effect indicates that combined treatment resulted in a greater than additive effect.…”

Section: Effect Of Hemicholinium-3 On the Hypotensive Response To Metmentioning

confidence: 89%

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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Section: Effect Of Hemicholinium-3 On the Hypotensive Response To Metmentioning

confidence: 89%

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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“…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: Discussionmentioning

confidence: 99%

“…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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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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“…Pargyline and a-methyldopa also produce a further blood pressure reduction in an upright position, but the effect does not appear to be related to venous pooling. With both drugs the cardiac output is maintained at normal levels in the erect position, while the increase in peripheral resistance is abolished (91,(93)(94)(95)(98)(99)(100).…”

Section: Herrlodynamics Of Hypertensionmentioning

confidence: 99%

The Hemodynamics of Hypertension and Anti Hypertensive Therapy

Bender¹

1966

Angiology

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It has been amply demonstrated that lowering systemic arterial pressure betters the prognosis of patients with hypertension. When the cause of the hypertension is known, the treatment of choice is the removal of the lesion. If the pathogenesis of the blood pressure elevation is unknown, however, treatment must necessarily be empirical and irrational. Despite this approach there is general agreement that controlling blood pressure with antihypertensive drugs results in a longer life expectancy for patients with essential hypertension and a reduction in the incidence of associated disabling cardiac, cerebrovascular, and renal complications (1, 2). HerrLOdynamics of hypertensionWhile there are some exceptions, especially in its early stages (3, 4), essential hypertension is associated with an increase in peripheral vascular resistance with a normal cardiac output (5-7). The cause of the elevation does not appear to be the result of increased sympathetic tone, but rather a narrowing of the resistance vessels brought about by progressive arteriosclerosis and, occasionally, degenerative changes in elastic tissue (5).Initially, it was suggested that each of the major vascular beds, with the exception of the kidney, contributed equally to the elevation in peripheral resistance. In the kidney resistance is slightly more intense, with the result that renal plasma flow is moderately reduced (8-10). On the other hand cerebral blood flow (11, 12), coronary blood flow (13), and hepatic blood flow (14,15) are within normal limits.The results of other studies (7, 16) indicate that the vasculature of skeletal muscle does not share in the increased resistance. Furthermore, the results suggest a parallel between the hemodynamic pattern of hypertension and that exhibited by normal subjects during mild exercise. In view of the unchanged cardiac output (7) and the increase in skeletal muscle flow, the results imply a reduction in flow to other major vascular beds.Objectives of antihyperten,sive therapy The primary objective of antihypertensive therapy is, of course, to reduce arterial blood pressure. It is equally apparent that it is desirable to decrease blood pressure by a mechanism which causes little or no compromise of cardiovascular function. From the examination of the relationship Blood pressure = peripheral vascular resistance X cardiac output at The University of Iowa Libraries on June 20, 2015 ang.sagepub.com Downloaded from

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The Acute Hemodynamic Effects of L-Alpha Methyldopa

Cited by 15 publications

References 0 publications

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

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

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

The Hemodynamics of Hypertension and Anti Hypertensive Therapy

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