The renin-angiotensin system (RAS) functions as a primary regulator in the short-term and long-term control of blood pressure. Pharmacologic inhibition of the RAS with angiotensin-converting enzyme (ACE) inhibition is effective for treating systemic hypertension and congestive heart failure. As a more specific therapy, the development of renin inhibitors has evolved through various approaches: specific renin antibodies, peptides developed from prosegments of renin precursor, oligopeptides related to pepstatin a universal inhibitor of aspartyl proteinase enzyme, and analogs of angiotensinogen (the renin substrate). Angiotensinogen analogs are promising as therapeutic agents because of high potency, metabolic stability, and good oral bioavailability. Ongoing research is directed towards the application of renin inhibition, the treatment of various cardiovascular disorders, and as a biological probe for understanding the role of the RAS in control of blood pressure and blood volume.

Systemic hypertension, a vascular disease with multiple origins, now is being linked to subtle abnormalities in glucose metabolism, which include insulin resistance and hyperinsulinemia. These conditions often occur together in patients with obesity, noninsulin-dependent diabetes, or both. Hyperinsulinemia and insulin resistance may cause systemic hypertension through multiple mechanisms. Insulin has a salt-retaining effect on the kidney. Also, insulin can augment catecholamine release, increase vascular sensitivity to vasoconstrictor substances, and decrease vascular sensitivity to vasodilator substances. In addition, insulin can increase production of tissue growth factors and help retain sodium and calcium in cells. Insulin resistance in patients can be treated with regular aerobic exercise, weight reduction, and a high-fiber diet. Pharmacologic approaches include hypoglycemic drugs, weight-reducing agents, and certain antihypertensive drugs that may have a favorable impact on both blood pressure and insulin resistance.