Effect of dopamine-beta-hydroxylase inhibitors on blood pressure and cardiac norepinephrine levels in rats subjected to immobilization stress.
Fusaric acid and its derivative, FD-008, are selective and potent dopamine-beta-hydroxyalse inhibitors in vitro and in vivo. Effects of the drugs on blood pressure and norepinephrine levels in the heart of spontaneously hypertensive rats (SHR) and normotensive control rats (NCR) in a state of increased sympathetic nerve activity induced by immobilization stress were investigated. The blood pressure of NCR rose immediately after the onset of stress. In SHR, the blood pressure did not rise after stress in spite of a marked increase in heart rate. Fusaric acid or FD-008 (100 MG/KG P.O.) given 4 hours before stress markedly inhibited the increase in blood pressure by stress in NCR and decreased blood pressure in SHR. The increase in heart rate in SHR during stress was completely inhibited by FD-008 but the increase in NCR was not inhibited. Endogenous norepinephrine levels in the heart were decreased by immobilization stress in NCR and SHR, and further significant decreases in norepinephrine levels were caused by FD-008 in SHR and NCR of fusaric acid in SHR. The effect of FD-008  was greater than that of fusaric acid. The effects of picolinic acid derivatives on blood pressure and norepinephrine levels in the heart were more remarkable in a stressed state than in a resting state. The present data support the hypothesis that the hypotensive action of picolinic acid derivatives may be attributable to the decrease in sympathetic nerve norepinephrine release caused by dopamine-beta-hydroxylase inhibition.
D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects*; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors*; D005669:Fusaric Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D009206:Myocardium / Q000032:analysis*; D009638:Norepinephrine / Q000032:analysis*; D010848:Picolinic Acids / Q000494:pharmacology*; D051381:Rats; D012149:Restraint, Physical; D013315:Stress, Psychological
D000959:Antihypertensive Agents; D010848:Picolinic Acids; D004299:Dopamine beta-Hydroxylase; D005669:Fusaric Acid; D009638:Norepinephrine