Renin inhibition.
OBJECTIVE
Initial attempts to inhibit renin in humans have faced numerous difficulties. Molecular modeling and X-ray crystallography of the active site of renin have led to the development of new orally active renin inhibitors, such as aliskiren. Recent preclinical and clinical data suggest that this drug may be of value for treating patients with cardiovascular and renal disorders.


RESULTS
The once-daily administration of aliskiren to hypertensive patients lowers blood pressure as strongly as, or more strongly than, standard doses of established angiotensin II type 1 receptor blockers. It further decreases blood pressure in combination with hydrochlorothiazide. The biochemical consequences of renin inhibition differ from those of angiotensin I-converting enzyme inhibition and angiotensin II antagonism, particularly in terms of angiotensin profiles and interactions with the bradykinin-nitric oxide-cGMP pathway and possibly the (pro)renin receptor.


CONCLUSIONS
Blockade of the renin-angiotensin system with angiotensin I-converting enzyme inhibitors, angiotensin II type 1 receptor blockers or a combination of these drugs has become one of the most successful therapeutic approaches in medicine. It remains unclear, however, as to how to optimize the renin-angiotensin system blockade to maximize cardiovascular and renal benefits. In this context, renin inhibition to render the renin-angiotensin system fully quiescent is a new possibility requiring further study.
Azizi
Michel
M
Université Paris Descartes, Faculté de Médecine, and Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France. michel.azizi@egp.aphp.fr
D000577:Amides; D000818:Animals; D005650:Fumarates / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D000093342:Prorenin Receptor; D000092502:Renin Inhibitors
D000577:Amides; D005650:Fumarates; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D012083:Renin; D000093342:Prorenin Receptor; D000092502:Renin Inhibitors; C446481:aliskiren