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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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