Exaggeration of experimental hypertension in rats by contraceptive steroids (Enovid)

The possibly additive pressor effects of contraceptive steroids were studied by treating hypertensive rats chronically with Enovid. Renal hypertensive rats were unaffected by drug treatment during the first 5 weeks, but, from the 6th to the 8th week, Enovid-treated rats had much higher systolic pressures than those given corn oil alone. However, these differences dwindled and became insignificant from the 9th to the 16th week despite continued treatment. Subsequently, other rats were pretreated with Enovid or corn oil for 5 weeks before hypertension was induced by implanting deoxycorticosterone acetate (Doca). In contrast to the equivocal results obtained previously, Doca hypertension was consistently more pronounced in rats treated with Enovid than in those given corn oil. This pressure difference was later verified by direct measurement of phasic aortic pressures from indwelling catheters and by the postmortem finding that Enovid-treated rats had larger hearts than corn oil-treated ones. The exact mechanism by which Enovid enhances Doca hypertension is still undetermined, but sympathetic hyperactivity was considered an unlikely explanation, since responses to posterior hypothalamic stimulation, norepinephrine, or ganglion blockade with pentolinium were unaltered.