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)

The response to ramipril, 10 and 20 mg on consecutive days, in 9 patients with severe (New York Heart Association functional class III or IV) chronic congestive heart failure was measured. Hemodynamic cannulae were placed more than 2 days before ramipril administration to ensure a stable baseline. Dietary sodium (40 mmol daily) and potassium (80 mmol daily) were constant before and during the study, and maintenance doses of digoxin and furosemide (80 to 1,000 mg daily) were continued unchanged. Ramipril induced pronounced, sustained decreases in angiotensin converting enzyme activity, angiotensin II and aldosterone levels, and a reciprocal increase in plasma renin activity. Plasma catecholamines, antidiuretic hormone and cortisol levels were not altered. Urinary sodium and potassium excretion diminished, plasma sodium decreased and plasma potassium increased. Plasma urea and creatinine levels increased. Ramipril treatment resulted in a decrease in systemic arterial pressure that was sustained for 24 hours, a decrease in heart rate and an increase in cardiac index, but little change in pulmonary artery pressure or right atrial pressure. Three patients were drowsy after ramipril administration, and 1 patient had a marked, temporary reduction in urine output. It was concluded that ramipril is a potent, long-acting angiotensin converting-enzyme inhibitor that is likely to be beneficial in patients with severe cardiac failure.
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PMID:Acute hemodynamic, hormonal and electrolyte effects of ramipril in severe congestive heart failure. 303 25

The emergence of diuretic drugs and angiotensin converting enzyme (ACE) inhibitors ranks amongst the major therapeutic advances of modern medicine. The discovery of these drug groups arose largely by chance, yet each has dramatically influenced the treatment of congestive cardiac failure and arterial hypertension. The central role which diuretics have had in the management of both oedema and hypertension hinges on their ability to induce a net renal excretion of solute and water by selective interference with either active or passive ion transport processes in different segments of the nephron. Irrespective of sites of action, the continued antihypertensive action of diuretics is characterized by a reduction in plasma volume and extracellular fluid (ECF) volume that lasts for as long as the diuretic is given. The mechanism of this effect remains unclear but may involve autoregulatory reactions that leave cardiac output unaltered but maintain a sustained reduction in total peripheral resistance. ACE inhibitors also lower blood pressure by decreasing total peripheral resistance, leaving cardiac output, plasma volume and ECF volume unchanged. The detailed way these haemodynamic changes are achieved remains unknown but inhibition of converting enzyme present not only in the kidney but also in many extrarenal tissue sites, appears important. In both hypertension and cardiac failure, however, the kidney acts as a key target organ for ACE inhibitors. The increased renal vascular resistance and inappropriate renal salt excretion are reversed with enhanced renal blood flow and saluresis. Both angiotensin II (AII) and vasopressin-mediated contraction of glomerular mesangial cells is inhibited, making glomerular filtration more efficient. Reduced aldosterone secondary to blockade of AII formation contributes to saluresis whilst encouraging positive potassium balance. ACE inhibition also impairs breakdown of kinins which may contribute to intrarenal and peripheral vasodilation either on their own or via release of prostaglandins and other vasoactive substances. The hypotensive actions of diuretics are potentiated by ACE inhibition primarily through blockade of AII formation and prevention of secondary aldosteronism. In combination, these drugs permit low doses to be used because of their synergistic effects. Caution has to be exercised whenever ACE inhibition is used, without and especially with diuretics, in the management of renovascular hypertension and other low-perfusion states. In these circumstances, AII plays an important autoregulatory role in preserving glomerular filtration through an increase in post-glomerular resistance.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Evolution of diuretics and ACE inhibitors, their renal and antihypertensive actions--parallels and contrasts. 303 17

Inhibition of the angiotensin converting enzyme (ACE) is associated with a decrease in renal vascular resistance, an increase in renal blood flow and a redistribution of intrarenal blood flow toward juxtamedullary nephrons. In general, ACE-inhibition does not affect normal glomerular filtration rate (GFR) but may increase GFR in patients on a low sodium intake prior to treatment. Since the rise in GFR is smaller than the rise in renal blood flow, in most instances a decrease in filtration fraction will result. In contrast to other vasodilator drugs, the decrease in blood pressure induced by ACE-inhibition is not accompanied by sodium retention, but rather by an initial natriuresis. ACE-inhibition also prevents secondary aldosteronism and thereby avoids renal potassium loss. The initial positive potassium balance after ACE-inhibition may protect patients with heart disease from potentially hazardous arrhythmias. Redistribution of intrarenal blood flow with increased medullary flow, in addition, will antagonize the hydrosmotic effect of vasopressin and thus result in a rise in free-water clearance. Finally, based on experimental evidence, long-term treatment with ACE-inhibitors may have a protective effect on renal function by reducing glomerular filtration pressure.
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PMID:[Inhibition of the angiotensin-converting enzyme--effect on kidney function and electrolyte balance]. 306 59

Nine elderly patients, some with preceding dementia, presented with adipsia, progressive dehydration, impaired consciousness, and hypernatremia following common acute infections without gastrointestinal disturbance. Studies before rehydration revealed inappropriately low plasma arginine-vasopressin (AVP) levels for plasma osmolality, insufficiently concentrated urine, absolutely or relatively low plasma angiotensin II (A-II) concentrations (compared with plasma renin activity and plasma angiotensin I concentrations), and low serum angiotensin I-converting enzyme activities. The plasma AVP concentrations were positively correlated with the plasma A-II concentrations (r = .677) but not with plasma osmolality. The plasma AVP level was raised by an intravenous infusion of A-II in one patient. These findings suggest the following sequence of events: impaired A-II production caused impairment of thirst perception, renal-concentrating capacity, and AVP secretion and contributed to development of hypernatremic dehydration in these elderly patients.
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PMID:Impaired arginine-vasopressin secretion associated with hypoangiotensinemia in hypernatremic dehydrated elderly patients. 327 39

The evidence presented here suggests strongly that the kallikreins-kininogens-kinins-kininase II system has most significant role in regulation of systemic BP. This system is involved in mediation and modulation of renin-angiotensin-aldosterone, PGS and vasopressin in the regulation of sodium water balance, renal hemodynamic and BP. Therefore, reduction in the kinin-formation due to high production of kininase II, and lower formation of tissue kallikrein might result in an increased release of vasoconstrictor angiotensin II on one side, and on the other side much reduced production of PGE, vasodilator. These changes might lead to deranged vascular smooth muscle structures and cell membrane functions, retention of sodium and water, increased plasma volume, and renovascular constriction. These physiological defects might result in the development of essential hypertension (Fig. 4). Although, it is possible now to treat hypertensive conditions with tissue kallikrein and kininase II inhibitors. These discoveries have opened up new vistas to research on the pharmacological applications of kallikreins-kininogens-kinins-kininases in human diseases.
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PMID:Interrelationship between the kallikrein-kinin system and hypertension: a review. 328 Mar 99

In hepatic cirrhosis neurohumoral vasoconstrictor systems are activated to compensate for circulatory disturbances. To study the renin-angiotensin-aldosterone system in more detail, angiotensin converting enzyme in 15 patients with advanced liver disease was inhibited with captopril after moderate sodium restriction. Captopril caused an increase in plasma renin activity (p less than 0.005) and a decrease in plasma aldosterone (p less than 0.025) from an elevated baseline, and a moderate drop in systolic (p less than 0.025) and diastolic (p less than 0.05) blood pressure. Hyperreninaemia after captopril was inversely related to the prevailing plasma sodium level (r = -0.66, p less than 0.01), and the changes in both systolic and diastolic blood pressure were correlated with baseline plasma renin activity (r = 0.49, p less than 0.05 for systolic and r = 0.71, p less than 0.01 for diastolic blood pressure). No change occurred in heart rate or in stimulated plasma noradrenaline and vasopressin levels. The data suggest that in these cirrhotic patients the reactivity of the renin-angiotensin-aldosterone system was still intact, although it occurred at a higher level. They confirm the importance of the renin-angiotensin-aldosterone system in arterial blood pressure regulation in cirrhosis.
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PMID:Effect of captopril on renin and blood pressure in cirrhosis. 331 47

Phenylephrine, vasopressin and glucagon each increased the amount of active (dephospho) pyruvate dehydrogenase (PDHa) in isolated rat hepatocytes. Treatment with 4 beta-phorbol 12-myristate 13-acetate (PMA) opposed the increase in PDHa caused by both phenylephrine and glucagon, but had no effect on the response to vasopressin: PMA alone had no effect on PDHa. As PMA is known to prevent the phenylephrine-induced increase in cytoplasmic free Ca2+ concentration ([Ca2+]c) and to diminish the increase [Ca2+]c caused by glucagon, while having no effect on the ability of vasopressin to increase [Ca2+]c, these data are consistent with the notion that in intact cells an increase in [Ca2+]c results in an increase in the mitochondrial free Ca2+ concentration, which in turn leads to the activation of PDH. In the presence of 2.5 mM-Ca2+, glucagon caused an increase in NAD(P)H fluorescence in hepatocytes. This increase is taken to reflect an enhanced activity of mitochondrial dehydrogenases. PMA alone had no effect on NAD(P)H fluorescence; it did, however, compromise the increase produced by glucagon. When the extracellular free [Ca2+] was decreased to 0.2 microM, glucagon could still increase NAD(P)H fluorescence. Vasopressin also increased fluorescence under these conditions; however, if vasopressin was added after glucagon, no further increase in fluorescence was observed. Treatment of the cells with PMA resulted in a smaller increase in NAD(P)H fluorescence on addition of glucagon: the subsequent addition of vasopressin now caused a further increase in fluorescence. Changes in [Ca2+]c corresponding to the changes in NAD(P)H fluorescence were observed, again supporting the idea that [Ca2+]c indirectly regulates intramitochondrial dehydrogenase activity in intact cells. PMA alone had no effect on pyruvate kinase activity, and the phorbol ester did not prevent the inactivation caused by glucagon. The latter emphasizes the different mechanisms by which the hormone influences mitochondrial and cytoplasmic metabolism.
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PMID:The glucagon-induced activation of pyruvate dehydrogenase in hepatocytes is diminished by 4 beta-phorbol 12-myristate 13-acetate. A role for cytoplasmic Ca2+ in dehydrogenase regulation. 359 19

The roles of vasopressin, the sympathoadrenal system, and the renin-angiotensin system in the production of hypertension after bilateral destruction of the nucleus tractus solitarius (NTS) were examined in chloralose-anesthetized rats. Since the activity of the renin-angiotensin system is high in anesthetized rats, additional studies were performed in unanesthetized, freely moving rats to evaluate the role of the renin-angiotensin system in hypertension caused by NTS lesions. Hypertension produced by bilateral electrolytic NTS lesions in rats was accompanied by elevated plasma levels of vasopressin (approximately 7-fold), norepinephrine (greater than 10-fold), and epinephrine (greater than 10-fold), but not of plasma renin activity. These results suggest that this form of hypertension is due to increased sympathoadrenal activity and increased vasopressin release into plasma and that the renin-angiotensin system is not involved. In rats with NTS lesions, blockade of vasopressin or the sympathoadrenal system, but not the renin-angiotensin system, elicited an acute decrease in arterial pressure. However, blockade of either vasopressin or the autonomic nervous system before production of the lesions had no effect on the resulting hypertension, indicating that in the absence of either one of these systems bilateral NTS lesions still result in severe hypertension. Although the renin-angiotensin system does not normally contribute to this hypertension, it does appear to contribute to the elevation in blood pressure once the actions of vasopressin have been blocked. In rats pretreated with a vasopressin antagonist, plasma renin activity increased following NTS lesions and the angiotensin converting enzyme inhibitor captopril decreased blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Peripheral pressor systems in hypertension caused by nucleus tractus solitarius lesions. 374 68

Oral administration of the angiotensin I-converting enzyme inhibitor captopril produced a substantial reduction of blood pressure in DOCA-salt hypertensive rats. After oral administration of captopril (30 mg/kg), mean blood pressure decreased from 172 +/- 11 to 148 +/- 9 mmHg (P less than 0.01) in one hour and its antihypertensive effects lasted for the next seven hours. Plasma vasopressin levels showed a marked elevation in DOCA-salt hypertensive rats compared with control values (22 +/- 5 versus 5 +/- 3 pg/ml). This increase in vasopressin was significantly reduced by captopril from 25 +/- 5 to 8 +/- 6 pg/ml. In addition, whole body vascular reactivity to norepinephrine was examined. Responsiveness was at first attenuated but returned to control value in spite of reduction of both plasma vasopressin and blood pressure. Thus, captopril reduces blood pressure in DOCA-salt hypertensive rats and the fall in blood pressure is accompanied by reduction of plasma vasopressin and attenuation of vascular reactivity.
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PMID:Depressor effects of captopril in DOCA-salt hypertensive rats: role of vasopressin. 389 13

Arterial blood pressures and heart rates were measured in water-replete and in water-deprived (48 h) conscious, adult rats that had received capsaicin (50 mg kg-1) or its vehicle neonatally. Resting arterial blood pressures and heart rates in capsaicin-treated rats were not different from the controls in either the water-replete or the water-deprived state. Inhibition of the vascular actions of vasopressin (with 1-beta-mercapto,-beta, beta-cyclopentamethylenepropionic acid, 8-D-arginine vasopressin, (d(CH2)5DAVP] had no significant effect on blood pressures in the water-replete animals but caused a significant hypotension in water-deprived rats; the magnitude of the hypotension was the same irrespective of whether the animals had received capsaicin or its vehicle. During angiotensin converting enzyme inhibition (with captopril) and ganglion blockade (with pentolinium), the vasopressin-mediated blood pressure recovery was more gradual in the capsaicin-treated animals than in the controls, but after 60 min blood pressures were similar in all groups. Collectively the results indicate that although the full development of vasopressin-dependent mechanisms following acute hypotension takes longer when a large proportion of unmyelinated afferent fibres have been destroyed by neonatal treatment with capsaicin, 48 h of water deprivation results in a normal involvement of vasopressin-dependent mechanisms in the maintenance of blood pressure.
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PMID:The influence of neonatal treatment with capsaicin on the control of blood pressure in adult rats in water-replete and water-deprived states. 389 38


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