The renin angiotensin system in the development of cardiovascular disease: role of aliskiren in risk reduction.
An association has been shown between plasma renin activity (PRA) and the risk of cardiovascular disease. There is also evidence that angiotensin II exerts detrimental effects on progression and instabilization of atherosclerotic plaque. The renin-angiotensin system (RAS) can be inhibited through inhibition of angiotensin I (Ang I) generation from angiotensinogen by direct renin inhibitors, inhibition of angiotensin II (Ang II) generation from angiotensin I by angiotensin-converting enzyme inhibitors and finally by direct inhibition of the action of Ang II receptor level. Aliskiren, the first direct renin inhibitor to reach the market, is a low-molecular-weight, orally active, hydrophilic nonpeptide. Aliskiren blocks Ang I generation, while plasma renin concentration increases because the drugs blocks the negative feed-back exerted by Ang II on renin synthesis. Because of its long pharmacological half-life, aliskiren is suitable for once-daily administration. Its through-to-peak ratio approximates 98% for the 300 mg/day dose. Because of its mechanism of action, aliskiren might offer the additional opportunity to inhibit progression of atherosclerosis at tissue level. Hypertension is an approved indication for this drug, which is also promising for the treatment of heart failure. The efficacy of this drug in reducing major clinical events is being tested in large ongoing clinical trials.
Verdecchia
Paolo
P
Department of Cardiology, Clinical Research Unit Preventive Cardiology, Hospital Santa Maria della Misericordia, and Fondazione Umbra Cuore e Ipertensione - AUCI Onlus, Perugia, Italy. verdec@tin.it
Angeli
Fabio
F
Mazzotta
Giovanni
G
Gentile
Giorgio
G
Reboldi
Gianpaolo
G
D000577:Amides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000808:Angiotensinogen / Q000378:metabolism; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004334:Drug Administration Schedule; D005650:Fumarates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D011498:Protein Precursors / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D016896:Treatment Outcome; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism; D000093342:Prorenin Receptor; D000092502:Renin Inhibitors
D000577:Amides; D000808:Angiotensinogen; D000959:Antihypertensive Agents; D002317:Cardiovascular Agents; D005650:Fumarates; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D012083:Renin; D025262:Vacuolar Proton-Translocating ATPases; D000093342:Prorenin Receptor; D000092502:Renin Inhibitors; C458319:ATP6AP2 protein, human; C446481:aliskiren