Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endogenous peptidases participate in a major way in the formation of peptide pressor substances such as angiotensin II (A II) and endothelin (ET) as well as in the degradation of depressor substances, e.g. atrial natriuretic peptide (ANP) or bradykinin. They include on the one hand the angiotensin converting enzyme (ACE) and endothelin converting enzyme (ECE), on the other hand kinase II for bradykinin and neutral endopeptidase 24.11 (NEP) for ANP. Inhibition of these enzymatic reactions leads to a decline of vasopressors A II and ET and conversely delays the break-down of vasodilatating bradykinin and ANP. The main haemodynamic consequence of this double inhibition is a reduced peripheral vascular resistance and decline of the blood pressure. The concurrent block of both systems (dual inhibition) is more effective than the isolated block of one substance. The first dual endopeptidase inhibitors were ACE inhibitors blocking the conversion of angiotensin I to A II and inhibiting at the same time the degradation of bradykinin by kininase II which is identical with ACE. At present further substances were synthetized with a dual inhibitory effect e.g. on ECE and on NEP (phosphoramidone, thiorphan, ecadatril etc.). Under experimental conditions they have a long-term antihypertensive effect on the vascular wall and heart muscle. The development of another dual ACE and NEP inhibitor has reached already the stage of clinical tests and the first clinical studies. The preparation omapatrilate in amounts of 2.5-80 mg significantly reduced the BP in a dose-dependent way in mild and medium advanced essential hypertension. Normalization of the blood pressure, i.e. a drop below 140/90 mm Hg, was achieved with omapatrilate monotherapy in as many as 83% of patients with hypertension stage I and in 53% patients with essential hypertension stage II. The drop of blood pressure after 20-80 mg/day depended on the degree of hypertension and was comparable or better than monotherapy with lisonopril 20 mg/day or amlodipine 10 mg/day. Treatment with omapatrilate was well tolerated. Dual peptidase inhibitors interfering with the formation of pressor substances and with the degradation of depressor substances seem to be a perspective class of antihypertensives also useful in the treatment of other cardiovascular diseases (heart failure, primary pulmonary hypertension). Before its final inclusion in the therapeutic pattern, further comparative and clinical mortality studies must be implemented.
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PMID:[Dual endopeptidase inhibitors--a new direction in the development of hypertensive agents]. 1104 16

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are increased in conditions with cardiac ventricular volume and pressure overload. The general physiological and potential therapeutic roles of natriuretic peptides in respiratory disease, right ventricular (RV) dysfunction, and pulmonary arterial hypertension (PAH) are reviewed. BNP levels can be used to differentiate between dyspneic patients with a pure respiratory defect and those with RV dysfunction. BNP levels also correlate with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) in patients with PAH (atrial septal defect, chronic thromboembolic disease, and scleroderma). BNP is a predictor of mortality in patients with primary pulmonary hypertension (PPH). These are important clinical implications in that a noninvasive blood test may be used to identify high-risk patients for more invasive procedures such as cardiac catheterization. BNP or NT-proBNP measurements may also be used to guide therapy (e.g., pulmonary vasorelaxants) in PAH since upregulation of the natriuretic peptide pathway has been shown to reduce cardiac hypertrophy and PAH. Additionally, there may be therapeutic potential via recombinant BNP or neutral endopeptidase inhibitors in RV dysfunction and PAH.
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PMID:The natriuretic peptides and their role in disorders of right heart dysfunction and pulmonary hypertension. 1536 14

B-type natriuretic Peptide (BNP) is elevated in conditions with ventricular volume and pressure overload. The physiological, diagnostic and therapeutic role of BNP in right ventricular (RV) dysfunction and pulmonary arterial hypertension (PAH) are reviewed in this article. BNP levels can be used to differentiate between breathless patients with a respiratory disease and those with PAH. BNP has been shown to correlate with mean pulmonary arterial pressure and pulmonary vascular resistance in patients with PAH, whether primary or secondary. BNP is also a predictor of mortality in patients with primary pulmonary hypertension. These are important clinical implications in that a non-invasive blood test may be used to identify patients who require more invasive procedures (such as cardiac catheterization). There is increasing evidence that BNP or NT-proBNP measurements may also be used to guide therapy (e.g. pulmonary vasorelaxants) in PAH. Enhancement of the natriuretic peptide pathway has been shown to reduce cardiac hypertrophy and PAH and hence, there may be therapeutic potential via recombinant BNP or neutral endopeptidase inhibitors in RV dysfunction and PAH.
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PMID:B-type natriuretic Peptide and the right heart. 1551 57