Modeling sex differences in the renin angiotensin system and the efficacy of antihypertensive therapies

The renin angiotensin system is a major regulator of blood pressure and a target for many anti-hypertensive therapies; yet the efficacy of these treatments varies between the sexes. We use published data for systemic RAS hormones to build separate models for four groups of rats: male normotensive, male hypertensive, female normotensive, and female hypertensive rats. We found that plasma renin activity, angiotensinogen production rate, angiotensin converting enzyme activity, and neutral endopeptidase activity differ significantly among the four groups of rats. Model results indicate that angiotensin converting enzyme inhibitors and angiotensin receptor blockers induce similar percentage decreases in angiotensin I and II between groups, but substantially different absolute decreases. We further propose that a major difference between the male and female RAS may be the strength of the feedback mechanism, by which receptor bound angiotensin II impacts the production of renin.