Enhancement of the anti-hypertensive effect of methyldopa and other anti-hypertensive drugs by carbidopa in spontaneously hypertensive rats.
1. A peripheral inhibitor of L-aromatic amino acid decarboxylase, carbidopa [(-)-L-alpha-hydrazino-3,4-dihydroxy-alpha-methylbenzenepropanoic acid monohydrate], at doses up to 25 mg/kg intraperitoneally or 30 mg/kg orally had no effect on directly recorded arterial pressure of spontaneously hypertensive rats derived from the Wistar/Okamoto strain. It enhanced, however, the anti-hypertensive effects of methydopa, hydrallazine, guanethidine and clonidine, and, to a lesser extent, reserpine and hydrochlorothiazide. The mechanism of this enhancement is presently unkonwn, but biochemical studies support the assumption that carbidopa is likely to reduce sympathetic nervous system activity. 2. The conversion of [3H]tyrosine (given intraperitoneally) to dopa (3,4-dihydroxypheylalanine) and catecholamines was measured in the hearts and adrenals of control rats and animals pretreated with carbidopa (100 mg/kg, intraperitoneally). Carbidopa significantly decreased the accumulation of 3H-labelled catecholamines in both organs and increased their total tyrosine content and the specific radioactivity of tyrosine.