FURTHER EVIDENCE FOR A PERIPHERAL SYMPATHICOLYTIC ACTION OF THE ANTIHYPERTENSIVE CICLETANINE IN RATS

The site and mechanism of action of the antihypertensive agent cicleta nine have been studied. In the pithed rat model, intravenous (i.v.) ci cletanine was able to reduce the elevated blood pressure induced by co ntinuous infusion of the alpha(1)-adrenergic agonist, methoxamine, in a dose-related manner. In strip preparation of the aorta from deoxycor ticosterone (DOCA)-salt-treated rats, cicletanine was found to prevent the contraction induced by 1 mu M noradrenaline. When subeffective do ses of phentolamine (0.25 mg/kg p.o.) plus cicletanine (3 mg/kg p.o.) were given together, a clear-cut antihypertensive effect was observed in DOCA-salt rats. Moreover, subchronic administration of cicletanine (30 mg/kg p.o.), during the one month period of DOCA-salt administrati on to produce high blood pressure readings, was able to prevent cardia c noradrenaline depletion. These data suggest that the antihypertensiv e effect of cicletanine, which is clinically well tolerated, may be du e to a multifactorial mechanism of its action, through which if might alter a number of physiological mediators while exercising a slight po tency on each of them.