Effects of oxybutynin on the cardiovascular system in dogs

: The effects of oxybutynin, an anticholinergic and antispasmodic agent, on the cardiovascular system were studied in comparison with those of atropine in anesthetized dogs. Oxybutynin (0.1-10 mg/kg, i.v.) caused a transient hypotension, tachycardia, increases in femoral, stomach, mesenteric and common carotid arterial blood flows and a decrease in renal arterial blood flow. Atropine (0.1-10 mg/kg, i.v.) caused a stronger and more prolonged hypotension with bradycardia, accompanied by weaker blood flow changes than those by oxybutynin. In open-chest dogs, oxybutynin caused increases in cardiac output and coronary sinus outflow and decreases in heart rate and left ventricular pressure. The agent augmented dLVP/dt/P at doses up to 3 mg/kg, i.v., but reduced it at 10 mg/kg, i.v. Atropine caused stronger cardiosuppressive responses than those of oxybutynin. Coronary sinus outflow was decreased by atropine, unlike in the case of oxybutynin. The pressor responses of norepinephrine, epinephrine and tyramine were potentiated by pretreatment with oxybutynin (15 mg/kg, i.v.). However, pressor or depressor responses induced by histamine, isoproterenol, serotonin and DMPP were unaffected by oxybutynin. Intraarterial injections of oxybutynin, atropine and papaverine caused femoral and renal arterial vasodilations dose-dependently, in the following order of potency: papaverine greater than oxybutynin greater than atropine. In the isolated blood-perfused canine papillary muscle preparation, oxybutynin and atropine caused a negative inotropic action, whereas papaverine caused a positive inotropic action. From the above results, it is suggested that oxybutynin has milder cardiosuppressive and hypotensive effects than atropine in terms of potency and duration of action, and in addition, oxybutynin has a vasodilating action probably ascribable to its anticholinergic and antispasmodic actions.