19-norprogesterone and Body-Weight

Fifty-day-old unilaterally nephrectomized and 1% saline-drinking Sprague-Dawley CD male rats were divided into three comparable groups on the basis of blood pressure, body weight, and fluid intake. The control group received vehicle only, the second group received 19-nor-progesterone [19-nor-pregn-4-ene-3,20-dione (19-Nor-Prog)] in a dose of 250 micrograms/24 h, and the third group received aldosterone-acetate (Aldo-Ac) in a dose of 125 micrograms/24 h, by means of Alzet osmotic minipumps implanted sc for 21 days. Both the 19-Nor-Prog- and the Aldo-Ac-treated rats became hypertensive to a similar degree in the course of the study. Rats given Aldo-Ac also developed polydipsia, decreased body weight, cardionephromegaly, and hypokalemia. The 19-Nor-Prog-treated rats showed no significant changes in heart and kidney weights. The hypertensinogenicity of 19-Nor-Prog is unrelated to significant changes in heart and kidney weight, as is the case with potent mineralocorticoids.

Topics: Animals; Blood Pressure; Body Weight; Drinking; Heart; Hypertension; Kidney; Male; Nephrectomy; Norprogesterones; Organ Size; Rats; Rats, Inbred Strains

The mineralocorticoid potency of 19-nor-progesterone was evaluated by both its effect on electrolyte excretion in adrenalectomized animals and its ability to cause hypertension and electrolyte changes in mononephrectomized, salt-loaded rats. The mineralocorticoid activity, measured using an adrenalectomized rat bioassay, indicated that 19-nor-progesterone was 2.5% as potent as aldosterone but did not antagonize the effect of aldosterone when both were administered. In mononephrectomized rats, the daily administration of 1 mg/day quickly caused an enhanced consumption of 1% saline and induced severe hypertension within 3-4 weeks. Some severely hypertensive animals had marked anemia, but other did not; as a group they were found to have hypernatremia and hypokalemia. Hypertensive animals were found during life to display a relative hypothermia and, at necropsy, to have heart and kidney enlargement with severe and extensive vascular lesions in both organs, but not adrenal hypertrophy. It is concluded that 19-nor-progesterone has the characteristics of a potent mineralocorticoid and, as such, is capable of causing hypertension. It is not yet clear why this should be accompanied by hypothermia.

Topics: Adrenalectomy; Aldosterone; Animals; Blood Pressure; Body Temperature; Body Weight; Drinking; Female; Hypertension; Kidney; Mineralocorticoids; Norpregnenes; Norprogesterones; Organ Size; Potassium; Rats; Rats, Inbred Strains; Sodium