Effect of an oral contraceptive on spontaneous running activity of female rats

Abstract

Dietary administration of Enovid® at 7.5 mg/kg of food for 11 days to intact female rats reduced their cyclic running activity and induced changes in vaginal cytology characteristic of estrus. There was a linear relationship between the logarithm of the dose of Enovid® ingested and the percent decrease in running activity from the average observed before drug administration. Dietary administration of norethynodrel, one of the two components of Enovid®, at 7.5 mg/kg of food for 21 days decreased the magnitude of the running activity slightly but failed to affect its cyclic nature. In contrast, dietary administration of mestranol at either 0.125 or 0.54 μg/kg of food for 24 and 29 days respectively reduced running activity and increased the length of the estrus cycle. Hence, the effect of Enovid® on the running activity of intact rats is probably attributable to the mestranol contained in it. An apparent escape from the effects of chronic administration of mestranol on spontaneous running activity was observed from 20 to 30 days after beginning treatment with either dose used. The escape was characterized by a reinitiation of cyclic running activity during chronic drug administration. Elucidation of the mechanism of the escape phenomenon will require further study.

Renal and Myocardial Adrenoceptors in Steroid Contraceptive‐induced Hypertension in Rats

“…We found that chronic low dose EE2/NG treatment caused an accelerated weight gain in rats, whereas EE2 alone had little effect on bodyweight. This finding is in contrast to those of Fregly (1972Fregly ( , 1973 and of Fowler et al (1985), who reported attenuated bodyweight gain when high doses of either an oestrogen (mestranol, 2 pg/day) or a progestagen (norethynodrel, 120 pg/day) were administered alone in the diet. High doses of oestrogen inhibit food intake via an action on the central nervous system (Wade 1972) and the presence of contraceptive steroids in the gut may reduce food intake by interfering with gastrointestinal function (Fregly 1973).…”

“…Oestrogen treatment (with and without progestagen) induced a gradual rise in SBP which was followed by renal and ventricular hypertrophy. This supports earlier data showing that combined OC induce mild hypertension in rats (Fregly 1972(Fregly , 1973. Progestagen (both NG and norethisterone) treatment alone also induced hypertension, but this was transient and unaccompanied by renal or ventricular hypertrophy.…”

“…Oral contraceptives (OC) induce hypertension in a small percentage of women (Royal College of General Practitioners 1977). Similarly, steroid contraceptives, administered orally or by injection, elevate systemic blood pressure in rats (Fregly 1972(Fregly , 1973Saruta et al 1975;Geraghty et al 1985). Although the precise mechanism of OC-induced hypertension is unknown, stimulation of the renin-angiotensin system is a major possibility.…”

Does Oral Contraceptive (Enovid) Treatment Enhance Renal Hypertension in Rats by Inducing Sympathetic Hyperactivity?

“…The daily dose of Enovid was 200/ag/rat (containing 134 yag of norcthynodre! and 3 jug of mestranol): this dose is about 5.6 times larger than that used clinically for contraception (12). To assess effects of autonomicblockade, systolic pressure and heart rate were recorded before, and I It after, oral administration of either mecamylamine hydrochloride (Inversine), 200 and 400 mg, or /)/.-propranolol hydrochloride (Inderal), 1.6 mg; doses expressed in amounts of the respective salt given per 100 g body weight.…”