Renin-angiotensin system inhibitors

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 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.

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. 

Answer This patient has congestive heart failure from long-standing hypertension. In addition, the patient has compromised liver function, limiting the choice of drug. Drugs that inhibit the renin-angiotensin system, specifically ACE inhibitors, are... 

Ang II inhibits renin secretion. The inhibition, which results from a direct action of the peptide on the juxtaglomerular cells, forms the basis of a short-loop negative feedback mechanism controlling renin secretion. Interruption of this feedback with inhibitors of the renin-angiotensin system (see below) results in stimulation of renin secretion. 

Inhibition of the renin-angiotensin system with ACE inhibitors or ARBs may be incomplete because the drugs disrupt the negative feedback action of Ang II on renin secretion and thereby increase plasma renin activity. Other antihypertensive drugs, notably hydrochlorothiazide and other diuretics, also increase plasma renin activity. Aliskiren not only decreases baseline plasma renin activity in hypertensive subjects but also eliminates the rise produced by ACE inhibitors, ARBs, and diuretics and thereby results in a greater antihypertensive effect (Figure... 

Other possible ovarian regulators include tumour necrosis factor-alpha, catecholaminergic input, luteinization inhibitor, gonadotrophinbinding inhibitors, oocyte maturation inhibitor and the ovarian renin-angiotensin system. Ovarian renin-angiotensin has been detected in follicular fluid (Lightman et al., 1989). 

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