Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Cardiac failure is a clinical syndrome of symptoms and signs, which can be confirmed by imaging or invasive haemodynamic techniques. It may be caused by systolic or diastolic dysfunction, but systolic dysfunction rarely occurs alone. It is important to ascertain the degree to which each contributes, and the precise aetiology of the condition, particularly in relation to surgically correctable lesions. 2. Non-pharmacological approaches including weight loss, salt restriction and lifestyle changes may be beneficial in some patients, and diuretics, which reduce the load on the heart, are the traditional baseline therapy. 3. Digitalis has been used where problems with contractility predominate, but its beneficial effect has been disputed, and expectations of improvement in patients in sinus rhythm should not be too high. 4. Vasodilators have been considered as the next line of treatment. Arteriolar dilators tend to increase cardiac output, but have little effect on pulmonary artery wedge pressure, and venodilators tend to have the opposite effect. Probably both actions are necessary and angiotensin converting enzyme (ACE) inhibitors, which have both, have proved effective in terms of symptoms and survival. 5. Various other inotropic agents have been tried. Phosphodiesterase inhibitors improve exercise tolerance, but may increase the probability of serious arrhythmias, already a significant cause of sudden death. beta 1-partial adrenoceptor agonists such as xamoterol have shown some promise, and anti-arrhythmic therapy has also been considered. 6. Drugs which prevent progression of myocardial damage would prove a great advance, and beta-adrenoceptor antagonists and calcium channel blockers appear to have considerable potential in this area.
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PMID:Treatment of congestive heart failure--state of the art and future trends. 257 53

In our studies we investigated the vasodepressor effects of bradykinin in vivo in normotensive and hypertensive subjects. Bradykinin was injected intravenously and intraarterially (40-6050 pM/kg) respectively was infused intraarterially (40-6050 pM/kg/min). The investigations were performed in 21 normotensives and 15 hypertensives. Bradykinin injections were performed after the following pharmacological interventions: salt restriction (10 mmol Na/d), salt loading (300 mmol Na/d), captopril (50 mg), ramipril (5 mg), lisinopril (20 mg), ketotifen (2 x 1 mg), indomethacin (2 x 50 mg), and propranolol (80 mg). The results show that bradykinin lowers blood pressure dose related by marked reduction in peripheral vascular resistance. The blood pressure reduction was strongly correlated with the increase in kinin concentration. This effect of bradykinin appears to be independent of changes in sodium metabolism, of beta adrenoceptors, of histamine-1 receptors, and of prostaglandins. ACE-inhibitors potentiate the blood pressure lowering effect of bradykinin about 20- to 50-fold. In case of an intraarterial injection of bradykinin in only 2-5% o the intravenously used dose of bradykinin are needed to produce an identical fall in blood pressure. From this experiments a pulmonary clearance rate of bradykinin over 95% can be calculated. In the pulmonary arteries bradykinin has no effect on the vascular resistance. In patients suffering from primary or renovascular hypertension the blood pressure response to bradykinin was enhanced. The bradykinin potentiating effect of the ACE-inhibitors was not altered in the hypertensives. In patients suffering from bradykinin hypertension or primary hyperaldosteronism bradykinin developed the same blood pressure lowering effect as in the normotensives.
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PMID:[Effect of bradykinin on systemic and pulmonary hemodynamics in the human]. 258 15

In female patients with intermitting or permanent inclination to oedemas and intake of diuretics after exclusion of cardiac, renal, venous and lymphogenic causes should be thought of the clinical picture of the idiopathic and diuretic-induced oedema, respectively. Pathophysiologically, the two forms underlie an activation of the renin-angiotensin-aldosterone system with subsequent retention of water and common salt. In these cases the intake of diuretics is not indicated and may lead to the chronification of the oedemas. Therefore the physician is confronted with the responsible task to finish the permanent intake of diuretics by adequate explanation of the pathophysiological and pharmacological connections and to care for the frequently neurotic female patients in this difficult time. For a short time a treatment with aldosterone antagonists can be recommended and first therapeutic experiments with the application of ACE-inhibitors were successful. A special diet poor in common salt is not necessary and in the individual case a psychotherapeutic treatment of the female patients should be carried out.
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PMID:[Idiopathic and diuretic-induced edema]. 258 25

In general, rises in systolic blood pressure to over 200 mm Hg during exercise with a workload of 100W are regarded as pathological. Excessive exercise blood pressure values are to be expected in principle in all hypertensives. However, there are so far no generally accepted criteria for diagnosis of isolated systolic exercise hypertension (with normal values of resting blood pressure). The incidence of isolated systolic exercise hypertension is estimated to be about 10% of a selected population. In patients with excessive rises in blood pressure during exercise who want to engage actively in sport, general measures (reduction of obesity, restriction of alcohol and salt intake) and endurance training should be recommended initially. For endurance training, sporting activities that involve dynamic exercise are to be recommended (walking, running, mountain hiking, cycling, swimming, cross-country skiing). Activities involving isometric exercise (rowing, diving, tennis) and sport of a competitive nature are not suitable. In moderately severe and severe hypertension (diastolic blood pressure values in excess of 105 mm Hg), sporting activities and endurance training are contraindicated. If the exercise blood pressure values cannot be lowered below 220 mm Hg with the general measures mentioned, pharmacotherapy is to be considered. The drugs of choice for suppressing excessive rises in blood pressure during exercise are beta-blockers. In this group, beta 1-blockers are to be preferred to non-selective beta-blockers because of the metabolic neutrality of the former. beta-Blockers without intrinsic sympathomimetic activity (ISA) lower the blood pressure-pulse rate product more effectively than beta-blockers with ISA. Alternatively, calcium antagonists of the verapamil type and ACE inhibitors can be employed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Management of hypertension in actively exercising patients. Implications for drug selection. 264 57

EXP6155 (2-n-butyl-1-[4-carboxybenzyl]-4-chloroimidazole-5-acetic acid) and EXP6803 (methyl 2-n-butyl-1-[4-(2-carboxybenzamido)benzyl]-4-chloroimidazole -5-acetate, sodium salt) are shown to be novel, nonpeptide, antihypertensive, specific angiotensin II receptor antagonists. In rabbit aorta, they competitively inhibited the contractile response to angiotensin II with pA2 values of 6.54 and 7.20 and did not alter the response to norepinephrine or KCl. In guinea pig ileum, both agents blocked the responses to angiotensin I and II and did not alter the responses to bradykinin and acetylcholine. A similar specific angiotensin II antagonism was shown in vivo in the spinal pithed rat model. In renal artery-ligated rats, a high renin hypertensive model, EXP6155 and EXP6803 given intravenously, decreased blood pressure with ED30 of 10 and 11 mg/kg, respectively. Both compounds did not alter blood pressure when given orally at 100 mg/kg. Unlike saralasin, EXP6155 and EXP6803 given intravenously did not cause a transient increase in blood pressure in the renal artery-ligated and normotensive rats. Our results indicate that EXP6155 and EXP6803 are selective angiotensin II receptor antagonists and antihypertensive agents. Since neither compound had partial agonist activities or bradykinin potentiation effects, unlike the existing peptide angiotensin II receptor antagonists and angiotensin converting enzyme inhibitors, respectively, they may represent preferred probes for studying the physiological roles of angiotensin II.
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PMID:Nonpeptide angiotensin II receptor antagonists. IV. EXP6155 and EXP6803. 265 19

1. Renal nerve discharge may contribute to renal arteriolar hyperplasia and hypertrophy but the kidney is not the major site of increased vascular resistance in hypertension. 2. Natriuretic and diuretic responses to dietary salt are dissociated in some SS hypertensives. Experiments with perfused rat kidneys indicate that this dissociation is due to circulating catecholamines and not to increased renal nerve activity. 3. Reduced tubular dopamine production may be involved in SS hypertension but decreased dopaminergic nerve activity is not apparent. 4. Increased salt intake initiates a generalized increase in vascular resistance in SS hypertensives. The small amount of salt retained over 5-7 days could not produce the observed increase in blood pressure by altering ECF volumes or transmembrane ion gradients which suggests that a systemic vasoconstrictor, such as renin, is involved. In these patients, inappropriate renal nerve activity could shift the balance between salt intake, blood pressure and renin release since low level renal nerve activity raises the blood pressure required to inhibit renin release. Reversal of SS hypertension with ACE inhibitors is consistent with this hypothesis.
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PMID:Renal nerves in the pathogenesis of hypertension: a review. 266 45

Short term angiotensin converting enzyme inhibition may induce a transient salt and water retention in patients with hypertension or heart failure. To verify the glomerular and tubular effects of short term converting enzyme inhibition, thirteen patients with mild to moderate essential hypertension (WHO I-II) were treated orally either with perindopril (4 mg o.d.) or captopril (25 mg b.i.d.) for one week. Both drugs reduced supine mean blood pressure significantly (p less than 0.01) (perindopril from 126 +/- 11 to 108 +/- 7 mmHg, mean +/- SD, and captopril from 132 +/- 12 to 121 +/- 16). Plasma volume (radio-iodinated albumin space) was unchanged while mean extracellular fluid volume (inulin space) increased although not significantly (from 5.05 +/- 1.32 l/sqm to 5.71 +/- 2.21 with perindopril and from 4.96 +/- 2.6 to 5.6 +/- 1.7 with captopril). Sodium clearance decreased (from 1.4 +/- 0.6 to 1.1 +/- 0.5 ml/min 1.73 sqm with perindopril, p less than 0.05, and from 0.97 +/- 0.44 to 0.88 +/- 0.51 with captopril, n.s.). In 9 patients (6 on captopril and 3 on perindopril) extra-cellular fluid volume increased simultaneously with reduction in glomerular filtration rate and in proximal tubule sodium re-absorption as well as an increase in distal tubule sodium reabsorption. In these patients the changes in proximal and distal tubule sodium reabsorption were significantly (p = 0.05) different from those of the patients with no extra-cellular fluid expansion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Volume of the extracellular liquid and renal function during short-term administration of angiotensin converting enzyme inhibitors in essential hypertension]. 267 Jun 57

The renin inhibitor CGP 29,287 was administered continuously for 7 days (30 mg/kg per day, intraperitoneally, via osmotic minipumps) to normotensive marmosets fed a low-salt diet. As a control, another group of marmosets was given vehicle only. After 7 days of treatment, the mean arterial blood pressure of the CGP 29,287-treated marmosets was significantly lowered by about 23 mmHg. Plasma immunoreactive total and active renin were increased 10- and sevenfold, respectively, whereas plasma renin activity (PRA) was reduced by 95%. Plasma angiotensin II (Ang II) and aldosterone were also reduced (by 97 and 85%, respectively). Serum angiotensin converting enzyme activity was unchanged and there were no differences in plasma concentrations of electrolytes, urea or creatinine between CGP 29,287-treated and control marmosets. These results indicate that although renin release is markedly stimulated after continuous administration of a renin inhibitor for 7 days, the formation of Ang II and aldosterone, the active hormones of the renin-angiotensin system, is substantially reduced.
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PMID:Biochemical effects of prolonged renin inhibition in marmosets. 268 8

Renal and hemodynamic effects of diet alone and of single oral doses of the nonsulphydryl angiotensin converting enzyme (ACE) inhibitor, benazepril (10 mg), were investigated in eight healthy volunteers under stable conditions of high salt intake (300 mmol NaCl/day) and low salt intake (10 mmol NaCl/day), in a double blind, placebo controlled study. There were no changes in blood pressure between the two dietary extremes either during the run-in period or once sodium balance had been achieved. Mean renal plasma flow was higher, by approximately 10% and renal vascular resistance lower by 15%, on high salt diet compared to low salt diet. Glomerular filtration rates were found to be similar irrespective of the state of salt balance. Both plasma urate concentration and plasma renin activity were significantly elevated in the low salt compared to high salt state. Benazepril caused a greater fall in blood pressure in the sodium depleted state. Significant increases in the mean renal plasma flow, in the order of 15-20%, were seen over 6 h postbenazepril when compared with placebo response, regardless of the level of salt intake. Glomerular filtration rate over the same period remained unaltered. Benazepril doubled the urinary excretion of sodium over the first 4 hours after dosing whilst on the low salt diet; the equivalent increase during salt loading was approximately 20%. These results suggest that benazepril may exert direct effects on renal tubular function additional to those achieved through ACE blockade.
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PMID:Effect of salt balance on the renal and hemodynamic actions of benazepril in normal men. 268 36

The interaction of blood pressure, salt intake and the inhibition of angiotensin converting enzyme activity with cardiac hypertrophy were examined in the Dahl rat model. Eight-week-old salt sensitive and salt resistant rats were each separated into two colonies, one of which was maintained on a low salt and the other on a high salt diet for three weeks, at the end of which time both salt sensitive colonies were hypertensive. Each colony was then separated into two groups, one received no medication the other was given lisinopril until normotension was achieved. After 11 weeks of therapy, intra-arterial blood pressures and heart rates were recorded. The rats were sacrificed and heart weight to body weight ratios were determined. Both untreated salt sensitive groups displayed marked cardiac hypertrophy which correlated well with diastolic blood pressure irrespective of salt intake. Lisinopril therapy lowered blood pressures to normotensive levels in all groups except for salt sensitive rats ingesting a high salt diet where, despite a 10-fold increase in drug dose, normotension was not achieved. Significant cardiac regression accompanied lisinopril therapy in rats receiving low salt diets but high salt intake severely attenuated regression in both strains. There was no significant correlation between heart weight and blood pressure in the treated groups. The results suggest that cardiac regression appears to be mediated by other factors besides ventricular afterload pressure and that high salt intake adversely affects blood pressure and heart weight response to lisinopril therapy.
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PMID:Cardiac hypertrophy in experimental hypertension: interaction of the sodium ion, blood pressure and lisinopril. 283 32


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