Effect of contraceptive steroid and enalapril treatment of systolic blood pressure and plasma renin-angiotensin in the rat

Previous work has demonstrated contraceptive steroid-induced hypertension in rats. Here, we examined the relationship between steroid-induced hypertension and components of the renin-angiotensin system. Female Sprague-Dawley rats were injected s.c. with 0.2 micrograms ethynyloestradiol, 2.0 micrograms levonorgestrel, a combination of both or vehicle, six days per week. A second group of rats received 2.0 micrograms enalapril maleate, enalapril plus ethynyloestradiol or levonorgestrel, or vehicle. Systolic blood pressure increased with both ethynyloestradiol. (6 weeks, +17 mmHg; 12 weeks, +32 mmHg) and levonorgestrel (6 weeks, +24 mmHg) treatment. This effect of levonorgestrel was attenuated by co-administration of enalapril, which also reversed the hypertension seen with ethynyloestradiol. Ethynyloestradiol, but not levonorgestrel treatment caused a significant increase in plasma renin concentration, plasma renin activity, and plasma angiotensin II at both 6 and 12 weeks. Plasma renin substrate was increased by ethynyloestradiol at 3, 6 and 12 weeks, prior to the observed increase in systolic blood pressure. Combined steroid treatment had less pronounced effects. Enalapril alone or in combination with ethynyloestradiol decreased plasma renin concentration, activity and angiotensin II, and in combination with levonorgestrel decreased plasma renin concentration, substrate and activity (6 weeks only) but not angiotensin II. The data indicate a positive relationship between hypertension and the renin-angiotensin system with ethynyloestradiol, but not levonorgestrel treatment in rats