Role of the renin-angiotensin aldosterone system in hypertension and blood pressure control

The primary aim of our research is to understand the role of the renin-angiotensin system in the regulation of blood pressure and tissue perfusion. We previously showed that this kidney-derived system reacts to maintain blood pressure and tissue perfusion when sodium intake is low and reciprocally turns off when sodium intake, perfusion pressure, or blood pressure are elevated. In certain people the system does not suppress appropriately. Such patients develop hypertension, which can be treated with anti-renin system drugs. In both population studies and in animal models we showed that hypertension associated with high renin levels is more likely to result in heart attacks and strokes than other forms of hypertension.

Current research questions address the mechanism whereby the renin system maintains pressure and tissue perfusion. We have recently developed evidence for a specific receptor for renin. Prorenin also binds to this receptor. We are now investigating the hypothesis that prorenin has two roles. Firstly, it is the biosynthetic precursor of renin in the kidneys. Secondly, it may be a natural competitive antagonist of renin, acting at specific target sites to protect vital organs from the ischemic effects of renin.

Specifically, our research involves the production of recombinant prorenin, infusion of recombinant prorenin into rats to determine its effect on blood pressure and tissue perfusion, biochemical characterization, and molecular cloning of the renin/prorenin receptor and immunohistochemical characterization of the prorenin-renin-angiotensin system in the kidneys of hypertensive rat models.