Inhibitors, renin-angiotensin

In some patients with hypertension and in all patients with cardiac failure, the renin-angiotensin system is activated to an undesired degree, burdening the heart. The consequences of diminished ANG II generation by ACE inhibitors are multiple. In patients with hypertension, blood pressure is reduced as a result... 

Renin-Angiotensin-Aldosterone System ACE Inhibitors Nuclear Factor-icB... 

Renin-Angiotensin-Aldosterone System Epithelial Na+ Channels ACE Inhibitors... 

Aliskiren blocks the renin-angiotensin-aldosterone system at its point of a activation, which results in reduced plasma renin activity and BP. It provides BP reductions comparable to an ACE inhibitor, ARB, or CCB. It also has additive antihypertensive effects when used in combination with thiazides, ACE inhibitors, ARBs, or CCBs. It is approved for monotherapy or in combination with other agents. 

Renin-angiotensin system, 5 148, 158 Renin inhibitors, 5 158—159 Rennets, 10 296 Rennin, 12 64 Reocorin... 

There have been sustained efforts in recent years to use the carrier systems of the brush-border membrane of intestinal mucosa to increase absorption of orally administered drugs [29] [30]. One system of particular interest is the intestinal peptide carrier (hPEPTl) whose physiological function is the absorption of di- and tripeptides and whose xenobiotic substrates include /3-lactam antibiotics, renin inhibitors, and angiotensin-converting enzyme (ACE) inhibitors [31]. 

E. H. Ulm, W. J. Greenlee, Inhibitors of the Renin-Angiotensin System Enzymes , in Design of Enzyme Inhibitors as Drugs , Eds. M. Sandler, H. J. Smith, Oxford University Press, Oxford, 1989, p. 146- 177. 

Fig. 1. Renin-angiotensin system. RI renin inhibitor, ACEI ACE inhibitor, ARB Ang II receptor blocker, Mas-R orphan G-protein coupled receptor.

Renal function impairment In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (eg, patients with severe CHF), treatment with ACE inhibitors and angiotensin receptor antagonists has been associated with oliguria or progressive azotemia and with acute renal failure or death (rarely). No dosage adjustment is necessary for patients with renal impairment unless they are volume-depleted. AIIRAs are not dialyzable. 

Scheme 9.1. Renin-angiotensin system with sites of blockade by inhibitors or antagonists.

A rather new development is the orally available renin inhibitor aliskiren. It was approved by the U.S. Food and Drug Administration in 2007 for the treatment of hypertension. As mentioned above renin is a protease released on various stimuli from the jux-taglomerula apparatus in the kidney. Its release is the limiting step in the whole renin-angiotensin cascade. Since renin is highly substrate-specific its inhibition can be expected to have very little unspecific side effects. The result of an effective blockade of this enzyme is a reduced angiotensin I and angiotensin II formation. In contrast to ACE-inhibition or ATi-receptor blockade, the plasma concentrations of both peptides stay low. No interaction with other systems like the Kallikrenin-Bradykinin system seems to take place. 

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