INFLUENCE OF DIFFERENT PROGESTOGENS ON BLOOD-PRESSURE OF NONANAESTHETIZED MALE SPONTANEOUSLY HYPERTENSIVE RATS

The aim of the study was to find out if synthetic progestins with significant antintineralocorticoid activity would have a beneficial effect on blood pressure. Male spontaneously hypertensive rats were treated daily for four weeks with different progestogens by subcutaneous injection. Arterial pressure of the conscious animals was measured at three-day intervals. Progestogens were dosed on the basis of their progestogenic activity, whereby the dosages corresponded to the 10-fold effective dose for inhibition of ovulation in rats. For comparison, spironolactone as well as progesterone itself were included in the study. After four weeks' treatment, plasma volume, extracellular fluid volume (ECFV) and the sodium and potassium concentrations in the plasma were measured. In control animals, there was a slight decrease in blood pressure over the four-week experimental period. Progesterone and spironolactone similarly influenced blood pressure. A new progestin with significant antialdosterone activity, dihydrospirorenone (code No. ZK 30.595), slightly but significantly decreased the ECFV, plasma sodium concentration and slightly but insignificantly decreased blood pressure as compared to vehicle-treated controls. Synthetic progestins lacking this antimineralocorticoid activity did not decrease blood pressure, but rather induced a slight increase in this animal model. The results clearly support the hypothesis that synthetic progestins, like endogenous progesterone,all of them with inherent antialdosterone activity, decrease the ECFV and so might have an impact on extracellular fluid hemostasis as well as blood pressure regulation.