Inhibition of dopamine beta-hydroxylase in blood vessels by picolinic acid derivatives in vivo and their anthypertensive effects.

The effect of picolinic acid derivatives, 5-butylpicolinic (fusaric) acid (FA), 5-(3',4'-DIBROMOBUTYL)PICOLINIC ACID(BPR2FA)and 50(N'N-dimethyldithiocarbamoilmethyl)picolinic acid (YP-279) on dopamine beta-hydroxylase in blood vessels in vivo was studied. Maximum inhibition of the conversion of 14C-dopamine (14C-DA) to 14C-norepinephrine (14C-ne) in rat aorta, mesenteric artery and renal artery was detected 30 min after FA and Br2FA (75 mg/kg) and 60 min after YP-279 (75 MG/KG). NE synthesis from 14C-DA returned to near control values by 6 hr in the blood vessels. NE levels of the aorta and mesenteric artery were sigkificantly reduced by 30 to 50% at 4 hr after Br2FA or FA (75 mg/kg). Dopamine beta-hydroxylase (DBH) activity, using tyramine as substrate, in heart, aorta, mesenteric artery and renal artery was markedly reduced. The concentrations of FA, Br2FA and YP-279 in rat blood following a single i.p, injection of each drug increase rapidly, reaching highest values in 0 to 30 min and decreasing slowly to 0 after 6 hr. These compounds did not affect the uptake of 3H-NE into the rat heart. These three compounds were found to lower blood pressure effectively in normal Wistar rats (above 25 mg/kg).