A comparative study of methyldopa and labetalol in the treatment of hypertension.
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1 Twenty patients with essential hypertension completed a double-blind, dose-tritrated, cross-over comparison of methyldopa and labetalol. 2 Average lying BPs (systolic/diastolic) were reduced by 28/15 mmHg with methyldopa and by 23/15 mmHg with labetalol. 3 Average standing BPs (systolic/diastolic) were reduced by 29/14 mmHg with methyldopa and by 29/15 mmHg with labetalol. 4 Both lying and standing heart rates were reduced with labetalol. 5 It is concluded that the antihypertensive properties of labetalol and methyldopa are similar but that larger patient populations are needed to study the relative incidence of subjective adverse effects. (+info)
Evidence for a predominantly central hypotensive effect of alpha-methyldopa in humans.
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We examined the time course and extent to which central and peripheral mechanisms contribute to the short-term effects of a 500-mg oral dose of alpha-methyldopa on supine mean arterial pressure, cardiac output, and total peripheral resistance, as well as its effects on total urinary excretion of norepinephrine and its metabolites, in five subjects with essential hypertension. Total peripheral resistance was reduced significantly 1 hour after alpha-methyldopa administration and remained so for the ensuing 7 hours of the study (p less than 0.05). A small but significant reduction in mean arterial pressure occurred 7 hours after the dose (p less than 0.05), while cardiac output did not change significantly. Total 24-hour urinary norepinephrine and metabolite excretion was reduced by 8.1 mumol (35% compared with placebo). The relative distribution of urinary norepinephrine metabolites was unaffected by alpha-methyldopa, and the catecholamine metabolites of alpha-methyldopa, alpha-methylnorepinephrine and alpha-methylnormetanephrine did not account for this reduction. Competitive inhibition of methyldopa transport across the blood-brain barrier and into the central nervous system by large oral doses of isoleucine antagonized most of the effect of alpha-methyldopa. The effects on total peripheral resistance were completely abolished, and small, insignificant changes during the 7-hour study were similar to those observed after placebo. Changes in mean arterial pressure were not significant; however, 24-hour total urinary norepinephrine and metabolite excretion increased by 6.1 mumol to 22.7 mumol (24.7 mumol excreted after placebo). Adding benserazide to the alpha/methyldopa-isoleucine dose regimen in an attempt to inhibit any residual, presumably peripheral, effects of alpha-methyldopa caused little, if any, further antagonism.(ABSTRACT TRUNCATED AT 250 WORDS) (+info)
The plasma noradrenaline and growth hormone response to alpha-methyldopa and clonidine in hypertensive subjects.
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The mechanism of the antihypertensive effect of alpha-methyldopa was compared with clonidine by administering equipotent single doses of clonidine (0.2 mg) and alpha-methyldopa (750 mg) to nine hypertensive patients. Plasma noradrenaline was followed for 8 h thereafter as an index of peripheral sympathetic activity. alpha-Methyldopa and clonidine produced the same hypotensive response at 6 and 8 h after dosing with a similar fall in plasma noradrenaline levels at these times. Linear regression analysis between the systolic blood pressure fall and the corresponding plasma noradrenaline fall, showed that the slopes of the two regression lines were similar for alpha-methyldopa as for clonidine. Equipotent doses of alpha-methyldopa and clonidine produce the same fall in plasma noradrenaline. This supports the current hypothesis that an alpha-methyldopa metabolite acts centrally, like clonidine, to reduce peripheral sympathetic activity. (+info)
Effects of methamphetamine and methyldopa on ethanol induced hypothermia in mice.
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The effects of D-methamphetamine HCl (1, 2 and 4 mg/kg, i.p.) and alpha-methyldopa (1, 2 and 4 mg/kg, i.p.) on rectal temperature and on ethanol (3 g/kg, i.p.)-induced hypothermia have been investigated in mice. Methamphetamine caused a dose-dependent hyperthermia, but methyldopa induced hypothermia, which decreased with increases in dose. Methamphetamine antagonized the hypothermic effect of ethanol, but methyldopa (1 and 2 mg/kg) did not affect it. Methyldopa (4 mg/kg), however, reversed ethanol hypothermia. Ethanol pretreatment significantly potentiated the hypothermic effect of methyldopa (4 mg/kg), and it prevented methamphetamine-induced hyperthermia. A possible central action for the tested drugs on biogenic monoamines and a peripheral component in their thermoregulatory effects are discussed in this report. (+info)
Factors associated with the blood pressures of children born to women who were hypertensive during pregnancy.
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At age 7.5 years the supine blood pressures of 216 children born to women who had been hypertensive during pregnancy were recorded. No associations were found between the blood pressures of the children and their mothers. The blood pressures of children whose mothers received methyldopa during pregnancy did not differ from those of children whose mothers had no specific treatment. Four boys whose mothers had taken methyldopa for more than 150 days had significantly lower systolic and diastolic pressures than those in whom the treatment had been of shorter duration. Significant findings from multiple regression analyses were: positive associations between boys' systolic and diastolic pressures and current weight, and diastolic pressure and maternal weight; negative associations between boys' systolic and diastolic pressures and birthweight; and a positive association between girls' systolic pressure and current weight. (+info)
Alpha-methyladrenaline: a possible active metabolite of alpha-methyldopa in the rat brain.
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To determine whether or not alpha-methyladrenaline (MA) is an active metabolite of alpha-methyldopa, a centrally-acting hypotensive compound, we measured MA in the rat brain using the high-performance liquid chromatographic electrochemical detection method. After five daily treatments of alpha-methyldopa given twice daily a dose of 40 mg/kg, we found trace amounts of MA in the hypothalamus and C1-C2 area (hypothalamus, 23.7 +/- 2.3 picomole/g, n = 7; C1-C2 area, 5.4 +/- 0.4 picomole/g, n = 4), as well as large amounts of alpha-methylnoradrenaline (MNA) (Hypothalamus, 16.6 +/- 0.4 nanomole/g, n = 7; C1-C2 area, 7.0 +/- 0.2 nanomole/g, n = 4). In these brain areas, the amount of endogenous adrenaline was reduced to 10.6% and 16.1% of the control values, respectively. The amounts of MA were only 9.0% and 6.2% of that of endogenous adrenaline in these respective areas whereas MNA was detected at approximately the same level as endogenous noradrenaline. These findings indicate that MA is synthesized from alpha-methyldopa to a very minute extent in the hypothalamus and C1-C2 area, and a large amount of MNA was synthesized in these areas. These are of interest considering the changes of endogenous adrenaline and noradrenaline. Our results raise doubts about the participation of MA on the main determinant of the central hypotensive effect of alpha-methyldopa. (+info)
Effects of antihypertensive drugs on blood velocity in rhesus monkeys.
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Increasing evidence suggests that higher blood velocity, by causing turbulence and high shear rates at the endothelial surfaces of arteries, may be important in the pathogenesis of atherosclerosis. In order to measure the effects of antihypertensive agents on blood velocity, an improved method has been developed for analysis of Doppler ultrasound velocity recordings. The audio signal from a Doppler velocity meter is subjected to spectral analysis; the sonagraph thus obtained is digitized with the use of a magnetic table on-line with a calculator. Four monkeys were maintained at a hypertensive baseline for six weeks by infusion of angiotensin and isoproterenol. The effects on blood velocity of 72-hour infusions of propranolol, clonidine, hydralazine, and methyldopa were studied. In doses that reduced diastolic pressure by 13--28%, propranolol decreased mean blood velocity (mv) by 17%, clonidine decreased mv by 14%, while methyldopa increased mv 12%, and hydralazine increased mv by 52% (p less than .00001). Antihypertensive drugs appear to have different effects on blood velocity; these differences may influence choice of antihypertensive drugs for the prevention of arterial disease. (+info)
On the mechanism of L-dopa-induced postural hypotension in the cat.
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1. The effects of L-DOPA on postural hypotension and carotid occlusion pressor effect were studied, mainly in cats; the recovery of the blood pressure upon tilting was used as a measure of postural hypotension.2. L-DOPA (30 mg/kg) partially depressed the carotid occlusion pressor effect and caused some degree of postural hypotension, L-DOPA (100 mg/kg) had more marked effects; the responses returned to control after 90 to 150 minutes. L-DOPA itself caused a pressor response in all cats.3. The dopa decarboxylase inhibitor N(1)-(DL-seryl)-N(2)-(2,3,4-trihydroxybenzyl) hydrazine (RO4-4602, 50 and 10 mg/kg) had no effect itself on the tilt response but completely prevented the effects of L-DOPA on the carotid occlusion pressor effect and postural hypotension.4. After RO4-4602 (3 and 1 mg/kg), L-DOPA (100 mg/kg) caused a brief rise of blood pressure followed by a longer lasting fall in horizontally-orientated cats (i.e. ;supine' hypotension). No postural hypotension was observed after L-DOPA under these conditions.5. Noradrenaline elicited only small and transient effects on postural hypotension, but dopamine's effects were more marked and longer lasting. Pressor dose-response relationships for noradrenaline were the same before and after L-DOPA, as well as in cats pretreated with L-DOPA for 4 days.6. In cats with kidneys and intestines removed, the tilt reflex was still present. Dose-response curves to L-DOPA were the same as in normal animals. RO4-4602 (3 mg/kg) prevented postural hypotension and block of the carotid occlusion pressor effect; supine hypotension was also observed after L-DOPA.7. The recovery response to tilting in spinal cats was markedly depressed or absent unless the blood pressure was elevated by angiotensin, in which experiments L-DOPA depressed the recovery upon tilting (i.e. induced postural hypotension).8. Blood pressure responses to tyramine were increased after 10 mg/kg of L-DOPA, but depressed after 100 mg/kg. The response to tyramine was not depressed, however, when RO4-4602 was given to block the dopa-dopamine conversion.9. The response to sympathetic stimulation in pithed rats was depressed after L-DOPA and dopamine, but not after alpha-methyldopa.10. alpha-Methyldopa (300 mg/kg) given acutely caused a moderate degree of postural hypotension and a more marked postural hypotension if given for two days.11. It is concluded that it is possible to differentiate between the supine and postural hypotension caused by L-DOPA and that supine hypotension is due to a central effect and postural hypotension to an extracerebral effect. Postural hypotension is discussed in relation to six hypotheses presented to explain its effect. Postural hypotension after L-DOPA is probably not due to a-adrenoceptor blockade, a central effect or any effect on the kidney. The most likely hypothesis is that L-DOPA forms dopamine which acts as a false transmitter in the peripheral sympathetic nervous system. (+info)