The effects of alpha-methyldopa on renal function in hypertensive patients

Mohammed, Shakil; Hanenson, Irwin B.; Magenheim, Herbert; Gaffney, Thomas E.

doi:10.1016/0002-8703(68)90290-1

Cited by 49 publications

(13 citation statements)

References 11 publications

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“…XXV, November 1969 role in the control of renin release (11), and methyldopa can produce at least partial adrenergic nerve blockade in man (6,12). Although there is no evidence that methyldopa impaired sympathetic reflexes in the present study, it is possible that the reduced plasma renin activity may be related to an effect of this drug on sympathetic neurones.…”

Section: Adrenergic Mechanisms Play An Importantmentioning

confidence: 49%

“…It has been demonstrated that methyldopa can produce partial adrenergic nerve blockade in man (6,12) and it is likely that this contributes to the hypotensive effect of this drug. Our observation that methyldopa can decrease plasma renin activity raises the Circulation Research, Vol.…”

Section: Adrenergic Mechanisms Play An Importantmentioning

confidence: 99%

“…Mohammed et al (6) also found that methyldopa decreased the renal vascular resistance in hypertensive patients in the supine position, a position presumed to be associated with minimal reflex sympathetic activity. Cannon et al (7) also observed a decrease in renal vascular resistance in 5 of 7 supine hypertensive patients treated with methyldopa and suggested that this drug might have a direct effect on renal vessels.…”

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confidence: 93%

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Effect of Methyldopa on Plasma Renin Activity in Man

Mohammed

Fasola

Privitera

et al. 1969

Circulation Research

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The effect of methyldopa on plasma renin activity was studied in one hypertensive and four normotensive human volunteers. Peripheral venous blood for the estimation of plasma renin activity was obtained with the subjects supine and in a 70° head-up tilted position before, during and, in two subjects, after treatment with oral methyldopa. Despite a reduction in mean arterial pressure, the plasma renin activity was decreased by methyldopa in each subject. The increase in plasma renin activity associated with tilting, however, was not significantly suppressed by methyldopa. These results indicate that treatment with methyldopa can simultaneously decrease mean arterial pressure and plasma renin activity and it is possible that these effects may be causally related.ADDITIONAL KEY WORDS renin-angiotensin system pressure-control antihypertensive drug hypotensive mechanism• It is generally believed that the mechanism of the hypotensive effect of methyldopa is partial sympathetic nerve blockade due to replacement of the natural transmitter norepinephrine by a less potent "false" transmitter amethyl-norepinephrine (1). However, both substances have been shown to have identical pressor potency in dogs (2, 3) and rats (4). These observations suggest that the hypotensive effect of methyldopa, at least in some species, may not be explained on the basis of a reduced potency of a-methyl-norepinephrine. Although the pressor potency of norepinephrine was reported to be more than that of amethyl-norepinephrine in man (5), only a small range of doses of these two amines has been tested.Recently, Mohammed et al. (3) found that, in contrast to reserpine or guanethidine, chronic treatment with methyldopa significantly reduced the vascular resistance of denervated hindlegs of dogs. Mohammed et al. (6) also found that methyldopa decreased the renal vascular resistance in hypertensive patients in the supine position, a position presumed to be associated with minimal reflex sympathetic activity. Cannon et al. (7) also observed a decrease in renal vascular resistance in 5 of 7 supine hypertensive patients treated with methyldopa and suggested that this drug might have a direct effect on renal vessels. In contrast, the adrenergic neuronal blocking drug guanethidine does not decrease renal vascular resistance in supine man (8). These results viewed collectively suggest that methyldopa may attenuate a mechanism of pressure control other than the sympathetic nervous system, e.g. the renin-angiotensin system. This possibility was investigated in human volunteers in the present study. MethodsFour normotensive healthy males aged 23 to 28 years, and one 45-year-old woman with essential hypertension were studied. The investigative nature of the study was explained to each subject and written consent to participate was obtained.

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Section: Adrenergic Mechanisms Play An Importantmentioning

confidence: 49%

Section: Adrenergic Mechanisms Play An Importantmentioning

confidence: 99%

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confidence: 93%

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Effect of Methyldopa on Plasma Renin Activity in Man

Mohammed

Fasola

Privitera

et al. 1969

Circulation Research

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“…In contrast, Mohammed et al (25) reported a preservation of both GFR and RPF in six hypertensive patients with mild renal impairment. Sannerstedt et al (26) also reported a preservation of RPF and GFR in 11 hypertensive patients.…”

Section: Drugs Interacfing With A-adrenergic Receptorsmentioning

confidence: 85%

Antiadrenergic Antihypertensive Drugs: Their Effect on Renal Function

Bernstein¹,

O’Connor²

1984

Annu. Rev. Pharmacol. Toxicol.

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Peripheral alpha antagonists not only preserve renal hemodynamics, but decrease RVR and maintain renal perfusion autoregulation in the face of decreased systemic perfusion pressures. On the other hand, central alpha agonists appear to have variable effects. Clonidine preserves RBF and GFR both acutely and chronically, guanabenz decreases RBF acutely but not chronically, and alpha-methyl dopa preserved RBF but decreases GFR. Beta blockers also have variable effects on RBF: the most-often-studied beta blocker, propranolol, has reduced RBF by 10-20% while other commonly used beta blockers, such as nadolol and metoprolol, may preserve RBF. This may reflect propranolol's inability to maintain renal perfusion autoregulation in the face of decreased systemic blood pressure. This failure of propranolol is not completely understood but may be a function of its lack of cardioselectivity or ISA (49). It is also possible that inhibition of renal vasodilators such as the kallikrein-kinin system plays a role (49). Finally, it appears that patients with normal renal vascular tone may be at highest risk to suffer decrements in RBF with beta blockers. Perhaps most importantly, the clinical impact of propranolol's effect on renal function is unclear, since the reductions in GFR have not been sufficient to produce azotemia.

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“…18 Antihypertensive agents differ in their effects on the kidney because of the different mechanisms by which they lower blood pressure. 3,19,24 Renal blood flow is reduced maximally by agents which lower cardiac output and may be increased by a direct relaxant effect on renal arterioles or by interference with sympathetic reflexes. Reports of renal hemodynamic changes with diazoxide have been conflicting.…”

Section: Discussionmentioning

confidence: 99%

Diazoxide and renal function in man

Johnson

1971

Clin Pharma and Therapeutics

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In 14 patients with hypertension, 4 mg. at diazoxide per kilogram of body weight iniected intravenously caused an 18 per cent reduction in mean blood pressure, 18 per cent reduction in para‐aminohippurate (PAH) clearance, 27 per cent reduction in inulin clearance, and 50 per cent reduction in uric acid clearance. Marked reduction in urinary sodium, potassium, and chloride excretion occurred. Whereas all of these effects were immediate in onset and sustained, free water clearance fell progressively in over half the subiects and became negative in 7 during the second hour after iniection. There was no correlation between antinatriuresis and change in renal hemodynamics, blood pressure, or tree water clearance. In 6 patients with hypertension, 2 mg. of diazoxide per kilogram injected intravenously caused no change in blood pressure or clearances of inulin or PAH. However, uric acid clearance fell 23 per cent, and clear reductions in urinary electrolyte excretion occurred. In 2 subiects, free water clearance fell progressively and became negative 1.5 to 2.5 hours after iniection. On a constant diet, 300 mg. of diazoxide daily by mouth caused weight gain and sodium retention with minimal change in blood pressure or creatinine clearance. This dosage did not alter free water clearance during sustained water diuresis. The acute antihypertensive effect of diazoxide is associated with reduced renal blood flow and glomerular filtration rate (GFR). Antinatriuresis can occur without change in blood pressure or GRF and is probably caused by a direct tubular action of diazoxide. Frequent marked reduction in free water clearance suggests stimulation of pituitary release of antidiuretic hormone. Diazoxide also suppresses tubular uric acid excretion.

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The effects of alpha-methyldopa on renal function in hypertensive patients

Cited by 49 publications

References 11 publications

Effect of Methyldopa on Plasma Renin Activity in Man

Effect of Methyldopa on Plasma Renin Activity in Man

Antiadrenergic Antihypertensive Drugs: Their Effect on Renal Function

Diazoxide and renal function in man

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