title: Inhibition of dopamine beta-hydroxylase in blood vessels by picolinic acid derivatives in vivo and their anthypertensive effects.
abstract: 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).
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents; D001011:Aorta / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003864:Depression, Chemical; D004299:Dopamine beta-Hydroxylase / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D006973:Hypertension; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010848:Picolinic Acids / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012077:Renal Artery / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D010848:Picolinic Acids; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine