Renin inhibition: a novel therapy for cardiovascular disease

The renin-angiotensin system (RAS) is a major contributor in the regulation of blood pressure, and pharmacologic manipulation of this system has resulted in a beneficial class of therapeutic agents, which include angiotensin-converting enzyme (ACE) inhibitors. However, ACE inhibitors are not specific for RAS, and in addition, they can affect bradykinin and prostaglandin, which can also cause changes in vascular tone. Under development are renin inhibitors that are specific for angiotensinogen and act at the initial, rate-determining step of the RAS cascade. The various pharmacologic approaches to renin inhibition include specific renin antibodies, synthetic derivatives of the prosegment of renin precursor, pepstatin analogs, and angiotensinogen analogs. The last approach is the most promising for patient therapy. Multiple studies have shown the effectiveness of the renin inhibitors in both primates and human beings. Further research is now directed toward the development of an agent with good oral bioavailability for patient treatment and as a biologic probe for helping to understand the role of the RAS in control of blood pressure and blood volume.