Captopril, enzyme inhibition

Chymostatin-sensitive Il-generating enzyme Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction Trial Collaborative Study Captopril Trial ( The Effect of Angiotensin-Converting Enzyme Inhibition on Diabetic Nephropathy ) calcium channel blocking agents Candesartan in Heart Failure Assessment of Reduction in Morbidity and Mortality Trial congestive heart failure, but the latest recommendations use HF for heart failure chronic kidney disease cardiac output... 

Bjorck JE. (1999) Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension The Captopril Prevention Project (CAPPP) randomised trial. Lancet 353 611-616. 

Ali SM, Laping NJ, Fredrickson TA et al. (1998) Angiotensinconverting enzyme inhibition attenuates proteinuria and renal TGFpimRNA expression in rats with chronic renal disease. Pharmacology 57 20-27 Ashab I, Peer G, Blum M et al. (1995) Oral administration of L-arginine and captopril in rats prevents chronic renal failure by nitric oxide production. Kidney Int 47 1515-1521 Bardoux P, Martin H, Ahoulay M et al. (1999) Vasopressin contributes to hyperfiltration, albuminuria, and renal hypertrophy in diabetes mellitus Study in vasopressin-deficient Brattleboro rats. Proc Natl Acad Sci USA 96 10397-10402... 

Scott RA, Barnett DB. Lower than conventional doses of captopril in the initiation of converting enzyme inhibition in patients with severe congestive heart failure. Chn Cardiol 1989 12(4) 225-6. 

Hansson L, Lindholm LH, Niskanen L, Lanke J, Hedner T, Niklason A, Luomanmaki K, Dahlof B, de Faire U, Morlin C, Karlberg BE, Wester PO, Bjorck JE. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension the Captopril Prevention Project (CAPPP) randomised trial. Lancet 1999 353(9153) 611-16. 

Textor SC, Tarazi EM, Novick AC, Bravo EL, Eouad EM. Regulation of renal hemodynamics and glomerular filtration in patients with renovascular hypertension during converting enzyme inhibition with captopril. Am J Med 1984 76 (suppi) 29-37. 

Luderer JR, Demers LM, Harrison TS, Hayes AH. Converting enzyme inhibition with captopril in patients with primary hyperaldosteronism. Clin Pharmacol Ther 1982 31 305-11. 

Laffel LM, McGill JB, Gans DJ. The beneficial effect of angiotensinconverting enzyme inhibition with captopril on diabetic nephropathy in normotensive IDDM patients with microalbuminuria. North American Microalbuminuria Study Group. Am J Med 1995 99 497-504. 

Captopril competitively inhibits angiotensin I-converting enzyme, resulting in the prevention of angiotensin I conversion to angiotensin II, a potent vasoconstrictor that also stimulates aldosterone secretion. This action results in a decrease in sodium and fluid retention, increase in diuresis, and a decrease in BP. 

Bradykinin increases because the enzyme inhibited by captopril, converting enzyme, normally degrades kinins in addition to synthesizing angiotensin II (see Figure 11-4). The answer is (D). The most potent vasodilator discovered to date is calcitonin gene-related peptide. The answer is (E). 

Peptidyl-dipeptidase A (angiotensin-I converting enzyme, ACE, EC 3.4.15.1) plays a pivotal role in the control of blood pressure [80]. It has been established that its active site contains an essential Zn-atom that functions like that of carboxypeptidase A [2], ACE is inhibited by peptides having a proline or aromatic amino acid at the C-terminal position. These observations as well as the similarities with the active site of carboxypeptidase A have allowed a rational design of effective inhibitors of ACE (e.g., captopril (3.4) and enalapril (3.5)) used in the treatment of hypertension [81]. 

Angiotensin-converting enzyme (ACE) inhibitors such as captopril exert a long-term reno-protective effect. Among other effects, they lower systemic blood pressure and renal plasma flow and effectively reduce urinary protein excretion. Renal delivery of ACE-inhibitors may increase this efficacy and reduce extra-renal side-effects. Renal targeting of an ACE-in-hibitor can also be useful in clarifying the contribution of local ACE inhibition to these reno-protective effects. 

Like captopril, enalapril selectively suppresses the rennin-angiotensin-aldosterone system, inhibits angiotensin-converting enzyme, and prevents conversion of angiotensin I into angiotensin 11. 

ACE) inhibitors, such as captopril. Up to 20% of these patients may develop a cough with ACE inhibitors. The cause is not known for certain, but it may be related to the accumulation in the lungs of bradykinin or other inflammatory mediators. Inhibiting ACE leads to an increase in bradykinin, which is normally broken down by this enzyme. The rash was originally attributed to a sulfhydryl group in captopril but is known to occur with other non-sutfhydryl-containing ACE-inhibitors. 

Captopril, many others Inhibit angiotensin converting enzyme Reduce angiotensin II levels reduce vasoconstriction and aldosterone secretion increase bradykinin Hypertension heart failure, diabetes Oral Toxicity Cough, angioedema teratogenic... 

Mercaptoacyl pharmacophore library. Zinc metalloproteases are inhibited by small molecules that contain mercaptans (thiols -CH2SH), carboxylic acids (-CO2H), and hydroxamic acids (-CONHOH). These functional groups chelate the active-site metal disrupting normal enzyme function. The angiotensinconverting enzyme (ACE) inhibitor Captopril is an example of a thiol-based metalloprotease inhibitor. Thiols, carboxylic acids, and hydroxamic acids are consequently affirmed pharmacophores for this protease family. A historical example of a pharmacophore-... 

FIGURE 50.2 Captopril and garlic inhibit angiotensin-converting enzyme. 

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