Direct renin inhibition with aliskiren in hypertension and target organ damage.
The Joint National Committee and the World Health Organization are in agreement that hypertension in most patients who are treated is controlled inadequately and that rates of cardiovascular morbidity remain high. Additional pharmacologic treatments could ameliorate this situation. The renin-angiotensin-aldosterone system has been a highly successful pharmacologic target, as the system is strongly implicated in the development of hypertension-related target organ damage. However, compensatory increases in plasma renin levels that lead to adjustments in angiotensin production and conversion present limitations for existing renin-angiotensin-aldosterone system inhibitors. A once-daily, orally effective, small-molecule renin inhibitor, aliskiren, is now available to address angiotensin production directly at its rate-limiting step. Studies in humans attest to an effective BP-lowering effect, a side effect profile no different from AT1 receptor blockers, and the option of combination therapies. A novel animal model of high human renin hypertension in the rat attest to target organ protection. Because angiotensin receptor blockade, angiotensin-converting enzyme inhibition, calcium channel blockade, and diuretic therapy all lead to sharp increases in plasma renin activity, aliskiren offers a novel circumvention.
Müller
Dominik N
DN
Medical Faculty of the Charité, Max Delbrück Center for Molecular Medicine, Franz Volhard Clinic, HELIOS Klinikum-Berlin, Berlin 13125, Germany.
Luft
Friedrich C
FC
D000577:Amides / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D005650:Fumarates / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D000092502:Renin Inhibitors
D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren