Prostaglandin E2-induced hyperplasia of the rat antral epithelium is followed by a secondary inhibition of the mitotic activity.

The aim of the study was to examine the mitotic activity in the antral and duodenal epithelium of Sprague-Dawley rats given trophic doses of E2 prostaglandins during a prolonged period of time. Natural prostaglandin E2 (dose range: 0.2-5.0 mg.k-1) and 15 (R) 15 methyl prostaglandin E2 (dose range: 0.03-2.0 mg.kg-1) were administered for 11 days, and mitoses were arrested with vincristine for 4 h before estimation of the cumulative mitotic index. A dose-related hyperplasia of the antral glands was observed after treatment with prostaglandin E2 and the synthetic analogue (p less than 0.05). The proliferative zone was enlarged in rats treated with high doses of the analogue but natural prostaglandin E2 did not affect the limits of the proliferative zone. A dose-related reduction of the mitotic index was observed in animals treated with prostaglandin E2 despite the presence of hyperplastic changes. All doses of the analogue induced antral hyperplasia without affecting the mitotic index except in rats given the highest dose who had a significantly lower mitotic index than controls (p less than 0.05). Hyperplasia of both crypts and villi was observed in the duodenum of rats given high doses of E2 prostaglandins (p less than 0.05) whereas the mitotic index and the growth fraction were not affected by treatments. It is concluded that hyperplasia by prostaglandins is developed in absence of changes of the mitotic activity. The observed reduction of the mitotic index is interpreted as a secondary phenomenon, possibly mediated by a regulatory mechanism of cell proliferation which is triggered to reduce further epithelial growth. It is suggested that prostaglandin E2 might influence such regulatory mechanisms.

Effects of (plus or minus)-propranolol, (plus or minus)-,(plus)-, and (minus)-alprenolol on unanaesthetized dogs with ventricular arrhythmias resulting from coronary artery ligation.

1. The effects of (+/-)-propranolol, (+/-)-, (+)- and (-)-alprenolol were studied in unanaesthetized dogs with ventricular arrhythmias produced by ligation of the left coronary artery. The responses were compared with those of similar control dogs which were given only isotonic saline.2. The ventricular arrhythmias were abolished by cumulative doses of 3.5 mg/kg of (+/-)-alprenolol, 7.5 mg/kg of (-)-alprenolol and (+/-)-propranolol and by 15.5 mg/kg of (+)-alprenolol.3. At the time of maximum antiarrhythmic activity none of the drugs produced significant alterations in mean arterial pressure or atrial rate.4. Cumulative doses of 7.5 mg/kg and 15.5 mg/kg of the four drugs resulted in some instances of lip licking, emesis and/or head tremors while 31.5 mg/kg was invariably lethal.5. Since the beta-adrenoceptor blocking activity of (-)-alprenolol is 100 times greater than that of (+)-alprenolol, suppression of these ventricular arrhythmias was apparently unrelated to antagonism of sympathetic influences.6. Alprenolol and propranolol have myocardial depressant properties apart from their effects on beta-adrenoceptors which could account for the anti-arrhythmic activity observed.