Central sympathoinhibitory action of a direct-acting vasodilator, budralazine, in anesthetized rats.
Previous data on budralazine, 1-[2-(1,3-dimethyl-2-butenylidene)-hydrazino]-phthalazine, has indicated that it is a direct-acting vasodilating agent that does not produce marked tachycardia. The present study was undertaken to elucidate what effects may be seen on the central sympathetic nerve activity when budralazine is given systemically to rats. Budralazine (0.5, 1.0 and 5.0 mg/kg, i.v.) produced a dose-dependent reduction of mean arterial pressure. At doses of 0.5 and 1.0 mg/kg, budralazine induced bradycardia accompanied with a decrease in cardiac sympathetic nerve activity. Preganglionic adrenal sympathetic nerve activity was also reduced by budralazine (1.0 mg/kg, i.v.). A dose of 0.5 mg/kg of budralazine neither influenced carotid sinus nerve activity nor augmented aortic depressor nerve activity. On the contrary, a high dose of budralazine (5.0 mg/kg) produced simultaneous increases in the heart rate and cardiac sympathetic nerve activity along with a marked suppression of aortic depressor nerve activity. Plasma norepinephrine and epinephrine concentrations were also increased at a dose of 5.0 mg/kg. These findings suggest that budralazine doses of 0.5 and 1.0 mg/kg may reduce the sympathetic outflow that is mediated via central sympathoinhibitory action. Baroreceptor-mediated tachycardia occurred after high dose budralazine (5.0 mg/kg) administration in anesthetized rats.
Yoshioka
M
M
First Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Yahagi
H
H
Minami
M
M
Saito
H
H
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D003714:Denervation; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013565:Sympatholytics
D000959:Antihypertensive Agents; D013565:Sympatholytics; D006830:Hydralazine; C006153:budralazine; D009638:Norepinephrine; D004837:Epinephrine