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)

In congestive heart failure (CHF) both the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone-system (RAAS) are activated. Both phenomena are only of short-term benefit and inevitably detrimental with prolonged activation. There are many possibilities for interaction between the systems, in particular when they are both in the activated state as in CHF. Renin release from the renal juxtaglomerular cells is stimulated by the SNS via beta 1-adrenoceptors. At a higher level of renal nerve stimulation there is recruitment of antinatriuretic and finally vasoconstrictor activity, mediated by alpha 1-adrenoceptors. The vasoconstrictor potency of angiotensin II (AII) involves both postsynaptic angiotensin II-receptors and also various processes stimulating sympathetic activity and its sequelae. The following sympathetic components may contribute to the effect of angiotensin II:ganglionic stimulation; enhanced release of noradrenaline (tyramine-like effect); inhibited noradrenaline re-uptake; facilitation of noradrenaline release via presynaptic AII-receptors; sensitization of postsynaptic alpha-adrenoceptors. The presynaptic AII-mechanism is probably the most sensitive and relevant process, which is also involved in the vasodilator activity of ACE-inhibitors.
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PMID:Interaction between the adrenergic and renin-angiotensin-aldosterone-systems. 353 60

Enalapril, a novel long acting angiotensin converting enzyme (ACE) inhibitor, was given orally to 12 patients with chronic heart failure (NYHA functional class III and IV) and cardiomegaly. The optimal dose averaged 17 mg given once-daily. Heart rate, systemic arterial blood pressure, pulmonary arterial pressure, right and left ventricular filling pressures and cardiac index were monitored during dose efficacy titration. Eleven patients were recatheterised 3 months later. After stabilisation of cardiac filling pressures, all patients had left ventricular filling pressures in excess of 20 mmHg. Enalapril increased cardiac index acutely by 34% but at 12 weeks follow-up, cardiac index was not different from control levels. Left ventricular filling pressure was reduced acutely by 36% and by 41% at 3 months. Heart rate, systemic arterial and right atrial pressures and plasma concentrations of aldosterone were reduced during the observation period. ACE activity was inhibited at the time of peak haemodynamic effect from 25.3 +/- 9.8 to 4.9 +/- 3.4 U/ml (P less than 0.01). Renin was markedly elevated. These changes were accompanied by marked and sustained clinical improvement and subjective well-being.
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PMID:Acute and long-term response to enalapril in congestive failure. 609 34

Enalapril, a novel angiotensin converting enzyme inhibitor, was given orally to 12 patients with chronic heart failure (NYHA functional class III and VI) and cardiomegaly. Heart rate, systemic arterial blood pressure, pulmonary arterial pressure, right and left ventricular filling pressures and cardiac index were monitored during dose efficacy titration. The optimal dose averaged 17 mg given once-daily. All patients were recatheterized three months later. After stabilization of cardiac filling pressures, all patients had left ventricular filling pressures in excess of 18 mmHg. Enalapril increased cardiac index acutely by 34% but at 12 weeks follow-up, cardiac index was not different from control levels. Left ventricular filling pressure was reduced acutely by 36% and by 41% at three months. Heart rate, systemic arterial and right atrial pressures and plasma concentrations of aldosterone were reduced during the observation period. Renin was markedly elevated. These changes were accompanied by marked and sustained clinical improvement and subjective well-being.
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PMID:Sustained haemodynamic effects of enalapril in left ventricular failure. 610 Jun 3

To assess the effects of enalapril eight hospitalized hypertensive patients on constant sodium intake were treated with incremental doses of this angiotensin converting enzyme blocking drug. After four days of placebo treatment enalapril was given in single daily doses, starting with 1.25 mg and increasing until blood pressure was adequately controlled. On the 1.25 mg dose, angiotensin II (AII) and blood pressure did not change significantly, despite a 50% reduction in converting enzyme activity. There were, however, significant increases in noradrenaline, renin and aldosterone. With high doses a more pronounced reduction in converting enzyme activity was found while AII, aldosterone and blood pressure all fell significantly. Renin levels rose, but noradrenaline and adrenaline were reduced. Orthostatic hypotension did not occur. With continued treatment renal vascular resistance decreased concurrently with enhanced natriuresis and a reduction in body weight. Plasma volume rose slightly. The data indicate that enalapril may lower blood pressure by converting enzyme inhibition, but sodium loss and a decrease in sympathetic activity are associated features.
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PMID:Physiological effects of short-term treatment with enalapril in hypertensive patients. 610 Jun 12

Renin is stored in synaptosomes of rat brain, separately from cathepsin D and intraneuronal angiotensin II (ANG II) has been demonstrated with the electron-microscope. Although the subcellular localization of other components of the renin-angiotensin system (RAS) have still to be investigated, these data suggest possible intracellular synthesis of ANG II in the brain. Brain ANG II is biochemically identical to the plasma peptide and corresponds to (IIe) 5-ANG II. The peptide level is unchanged after bilateral nephrectomy, and angiotensin I (ANG I) accumulation is observed in nephrectomized animals following brain angiotensin converting enzyme blockade. The significantly greater accumulation of ANG I and reduction of ANG II in stroke prone spontaneously hypertensive Wistar-Kyoto rats (WKY) indicates a higher synthesis and turnover rate of ANG II in SHR. Most converting enzyme inhibitors (CEI) penetrate the brain after chronic oral treatment. Part of their blood pressure lowering action may therefore be explained by an inhibition of the brain RAS.
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PMID:The brain angiotensin system: subcellular localization and interferences with converting enzyme inhibitors. 610 Jun 13

The role of the renin-angiotensin system in the control of blood pressure in normal rodents, primates and man has been evaluated using inhibitors which block the system at various stages. Renin plays a major role in the maintenance of blood pressure under volume depletion. In subjects with a normal salt intake, the contribution of the renin-angiotensin system in maintaining blood pressure levels can be evaluated using angiotensin converting enzyme (ACE) inhibitors. The contribution of the renin-angiotensin system can now be evaluated more closely following the development of new substances which block the renin-angiotensinogen reaction. Available data strongly suggest that renin contributes to the maintenance of blood pressure levels in subjects with a normal salt intake, although to a lesser degree than in subjects on a low sodium intake. The renin-angiotensin system plays a role in the regulation of blood pressure levels in normal experimental animals and man--its importance depending on the state of sodium balance.
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PMID:The role of the renin-angiotensin system in blood pressure regulation in normotensive animals and man. 610 Aug 73

There are several approaches for interfering with the renin-angiotensin system. Antibodies against renin and angiotensins I and II (AI and AII) have not been consistently successful in the past, probably because of nonspecific effects; however, recent purification of renin now makes this approach more promising. Renin inhibitors include pepstatin and analogs, lipids and phospholipids, and renin-substrate analogs. Pepstatin and analogs are the most potent and specific but they are not orally active. The phospholipids are the most effective in vivo but their specificity is yet to be established. Renin-substrate analogs have been developed that have biologically significant effects but are not orally active. Some of the most potent and specific agents available for interfering with the renin-angiotensin system are the AII receptor antagonists. While these compounds effectively prevent the actions of AII, they suffer from several severe deficiencies: partial agonist activity, short duration of action, and lack of oral activity. The recent development of angiotensin-converting enzyme (ACE) inhibitors that are orally active has provided the greatest degree of clinical success for inhibitors of the renin-angiotensin system and, consequently, the impetus to develop still better compounds. Captopril (SQ 14,225) is the prototype ACE inhibitor, being highly potent and specific with no other demonstrated pharmacological activity. Captopril is effective in all forms of human and animal models of hypertension except mineralocorticoid hypertension, which requires concomitant diuretic therapy. Because ACE is the same enzyme as kininase II, the enzyme that degrades kinins, the possibility exists that kinins are involved in the cardiovascular action of captopril, although this prospect is unlikely.
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PMID:Inhibitors of the renin-angiotensin system as new antihypertensive agents. 617 73

There are several approaches for interfering with the renin-angiotensin system. Antibodies against renin angiotensins I and II (AI and AII) have not been consistently successful in the past, probably because of nonspecific effects; however, recent purification of renin now makes this approach more promising. Renin inhibitors include pepstatin and analogs, lipids and phospholipids, and renin-substrate analogs. Pepstatin and analogs are the most potent and specific but they are not orally active. The phospholipids are the most effective in vivo but their specificity is yet to be established. No renin-substrate analogs have been developed that have biologically significant effects. Some of the most potent and specific agents available for interfering with the renin-angiotensin system are the AII-receptor antagonists. While these compounds effectively prevent the actions of AII, they suffer from several severe deficiencies: partial agonist activity, short duration of action, and lack of oral activity. The recent development of angiotensin-converting enzyme ACE) inhibitors that are orally active has provided the greatest degree of clinical success for inhibitors of the renin-angiotensin system and, consequently, the impetus to develop still better compounds. Captopril (SQ 14,225) is the prototype ACE inhibitor, being highly potent and specific with no other demonstrated pharmacological activity. Captopril is effective in all forms of human and animal models of hypertension except mineralocorticoid hypertension, which requires concomitant diuretic therapy. Because ACE is the same enzyme as kininase II, the enzyme that degrades kinins, the possibility exists that kinins are involved in the cardiovascular action of captopril, although this prospect is unlikely.
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PMID:Drugs inhibiting the renin - angiotensin system. 626 16

We investigated the alteration of the ACE in different parts of the circulation in 21 patients with essential hypertension, who suffered from angina pectoris attacks. Blood samples were taken during diagnostic cardiac catheterisation. The ACE was fluorimetrically measured and compared to 48 normotensive patients. In 11 patients the Plasma Renin Activity (PRA) was additionally determined by means of bioassay. The ACE was significantly (p less than 0.001) elevated in all investigated regions but a different distribution was not observed. We found a positive correlation between the ACE from the left ventricle and the systolic, mean arterial and diastolic blood pressure. Furthermore, we observed a negative correlation between ACE and PRA. No relationship could be calculated between ACE and electrolytes, creatinine or haemodynamic parameters. Our results indicate that the ACE may contribute to the pathogenesis of so-called essential hypertension.
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PMID:Elevated angiotensin-I-converting enzyme (ACE) in patients with essential hypertension. 628 14

Direct renal effects of angiotensin I converting enzyme inhibitors (CEIs), captopril, SA446 and MK421, were examined in isolated rat kidneys perfused with a renin-substrate-free medium. Among three CEIs, only captopril induced a significant natriuresis, whereas SA446 and MK421 did not. UKV, renal vascular resistance and creatinine clearance were not affected by any of these CEIs. Renin release from perfused rat kidneys were not influenced by CEIs under the present experimental conditions. These results suggest that among three different types of CEIs, only captopril possesses natriuretic action in the isolated perfused rat kidney and that this action may be independent of its inhibitory action on angiotensin converting enzyme. It is also suggested that these three CEIs themselves do not have a direct effect on the renal vascular bed.
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PMID:Effects of angiotensin I converting enzyme inhibitors on the renal excretory function, hemodynamics and renin release in isolated perfused rat kidney. 632 82


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