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)

It was demonstrated that angiotensin I-converting enzyme was excreted in human urine. The mean activity of the enzyme in normal urine was found to be 0.38 +/- 0.04 (S.E.M.) units/day (n = 18) and the enzymic activity correlated well with the concentration of the excreted sodium (r = 0.76, p less than 0.005). Urinary angiotensin I-converting enzyme was partially purified. Three different molecular weights of enzyme (greater than 400 000, 290 000 and 140 000) were demonstrated by Sephadex G-200 gel filtration. The enzymic properties of these three enzymes were identical with those of angiotensin I-converting enzyme from human lung with regard to inhibitory effects (bradykinin potentiator c and Arg-Pro-Pro), Cl- dependency, pH optimum and KM value.
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PMID:Angiotensin I-converting enzyme in human urine. 3 May 52

Intravenous infusions of sodium nitroprusside (SNP) at doses of 20, 40 or 80 micrograms/kg min-1 for 30 min produced dose-related decrements in blood pressure in conscious rats fitted with indwelling aortic and vena caval catheters. Immediately upon termination of SNP infusions, blood pressure rebounded to levels which were significantly above pre-SNP control values. The following evidence indicates that the rebound increase in blood pressure was due to increased activity of the renin-angiotensin system: (1) plasma renin activity was increased approximately four-fold by SNP, (2) rebound did not occur in nephrectomized rats, (3) rebound was markedly attenuated in animals treated with an angiotensin converting enzyme inhibitor, SQ14225, (D-3-mercapto-2-methylpropanoyl-L-proline) and (4) beta-adrenergic receptor blockade with propranolol reduced the rebound response. In addition, the magnitude of the rebound following SNP infusions was directly related to the dose of SNP infused. These results are consistent with the hypothesis that renin accumulates during SNP infusion more rapidly than it is metabolized. Consequently, the accumulated renin elicits a hypertensive response when SNP treatment is withdrawn.
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PMID:Role of the renin-angiotensin system in the blood pressure rebound to sodium nitroprusside in the conscious rat. 4 20

1. The acute effects of the kallikrein inhibitor aprotinin (498 ki.u./min), and the kininase II inhibitor SQ 14,225 (250 MICROGRAM), GIVEN INTRAVEnously during saralasin-induced angiotensin blockade, were studied in conscious sham-operated rats and rats with benign and malignant two-kidney, one-clip Goldblatt hypertension during dietary sodium restriction. 2. The blood pressure of conscious sham-operated rats increased significantly in response to aprotinin. It remained unchanged after SQ 14,225 in contrast to the significant vasodepressor effect seen when SQ 14,225 was given to the same rats under surgical stress and pentobarbital anaesthesia. 3. Benignly hypertensive rats showed a consistent vasopressor response to aprotinin and a marked vasodepressor response to SQ 14,225. The effects of both inhibitors were markedly and significantly blunted in malignantly hypertensive rats. 4. Our demonstration that two agents with known opposite actions on the kallikrein-kinin system produced predictable and opposite effects on blood pressure may indicate that this system is involved in the homeostatic regulation of blood pressure. It may play an important antihypertensive role in benign two-kidney, one-clip Goldblatt hypertension, a role which might be impaired in malignant hypertension.
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PMID:The kallikrein-kinin system in blood pressure homeostasis. 9 77

The activities of the Na+--K+-ATPase, succinic dehydrogenase (SDH/, lactic dehydrogenase (LDH/ and glucose-6-phosphat dehydrogenase (G-6-PDH/ were studied in the cortex outer and inner medulla of the kidneys of rats with spontaneous hypertension (SHR) and were compared with those of control normotensive Wistar rats. The SHR aged 6--8 weeks had durint the prehypertensive and the early hypertensive stage the same enzymatic activities as control rats. Rats with a steady SH aged 16-22 weeks had low specific activity of the, Na+--K+-ATPase, SDH and LDH in the outer medulla. The latter can be associated with decreased intensity of the energy metabolism and a reduction of the active sodium transport in the ascending limb of the loop of Henle in the SHR rats and cold cause the phenomenon of exaggerated natriuresis characteristic of hypertension.
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PMID:[Na+--K+-adenosine triphosphatase and some oxidoreductases in the kidney of rats with spontaneous hypertension]. 12 6

In chloralose-anesthetized dogs, we investigated the disappearance of bradykinin on passage across the renal circulation. The peptide was infused into a renal artery at various doses (5-200 ng/kg min-1); renal blood flow and the concentration of kinins in renal venous blood were then determined and the percent survival of bradykinin on passage through the kidney calculated. Bradykinin caused a dose-related increase in renal blood flow, urine flow, sodium excretion, and kinin content of renal venous blood. Intravenous administration of BPP9alpha (300 mug/kg), a peptide kininase II inhibitor, potentiated the renal vasodilator, diuretic, and natriuretic actions of bradykinin and augmented the survival of the kinin on passage through the kidney from 12.72 +/- 1.64% in control dogs to 53.92 +/- 7.48% (P less than 0.001). Furthermore, the values of peptide survival were positively correlated with the increases in renal blood flow (r = 0.92, P less than 0.01), urine flow (r = 0.75, P less than 0.01), and sodium excretion (r = 0.68, P less than 0.01) produced by bradykinin. In addition, BPP9alpha by itself increased renal blood flow (16%, P less than 0.01), urine flow (115%, P less than 0.005), and sodium excretion (167%, P less than 0.02). Similarly, the concentration of kinin in renal venous blood and the excretion of urinary kinins rose from 0.11 +/- 0.03 ng/ml and 4.1 +/- 1.1 ng/min to 0.24 +/- 0.05 ng/ml (P less than 0.005) and 38.5 +/- 12.2 ng/min (P less than 0.02). These studies suggest that kinins generated intrarenally play a role in the regulation of renal blood flow and salt-water excretion and that variations in the capacity of the kidney to inactivate kinins may be a determinant of the intrarenal activity of the kallikrein-kinin system.
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PMID:Disappearance of bradykinin in the renal circulation of dogs. Effects of kininase inhibition. 16 99

To examine the role of angiotensin II in the maintenance of blood pressure and the control of aldosterone secretion in man, eight normal subjects were studied on a tilt table in sodium replete and sodium depleted states prior to and subsequent to the intravenous infusion of an angiotensin converting enzyme inhibitor (CEI). In both the sodium replete or sodium depleted state, upright tilting resulted in an increase in heart rate and a narrowing of pulse pressure. None of the sodium replete or depleted subjects fainted. Tilting was accompanied by a rise in plasma renin activity with an associated rise in plasma aldosterone concentration. When converting enzyme inhibitor was administered, which blocked the generation of angiotensin II, sodium replete subjects were able to compensate for an upright tilt, despite the absence of angiotensin II, without significant hemodynamic change when compared to control state. In sodium depleted subjects, after the administration of converting enzyme inhibitor, there was a sharp and significant decrease in systolic and diastolic blood pressure associated with a significant rise in heart rate. All but one sodium depleted subject fainted within seven minutes. Both plasma aldosterone concentration and plasma renin activity rose on tilting in both sodium replete and sodium depleted subjects. After the administration of converting enzyme inhibitor, plasma aldosterone failed to rise in association with a rise in plasma renin activity. In supine subjects, after the administration of converting enzyme inhibitor, plasma renin activity rose but plasma aldosterone concentration fell. In sodium depleted subjects, after the administration of CEI, aldosterone fell to a level significantly lower than that in supine controls and to a level no different from the supine sodium replete subject. These results indicate that angiotensin II is essential for blood pressure maintenance in sodium depleted individuals, that angiotensin II exerts a direct feedback control on renin secretion, and that angiotensin II is the primary stimulus to aldosterone secretion in response to both sodium depletion and to posture.
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PMID:The role of the renin-angiotensin-aldosterone system in cardiovascular homeostasis in normal human subjects. 17 34

The solubilization of angiotensin I-converting enzyme (peptidyldipeptide hydrolase, EC 3.4.15.1) from rabbit lung was carried out using trypsin treatment. A good recovery of 76% was obtained. The enzyme from solubilized fraction was purified using colums of Sephadex G-200, hydroxyapatite and DEAE-cellulose. The purified enzyme was shown to convert angiotensin I to angiotensin II and also to inactivate bradykinin. The specific activity of the enzyme was 24.3 units/mg protein for hippurylhistidylleucyl hydroxide and 0.182 mumol/min per mg protein for angiotensin I. The enzymic activity obtained after trypsin treatment for 5 h could be divided into two components: (i) an enzyme of molecular weight 300 000 (peak II) and (ii) an enzyme of molecular weight 145 000 (peak III), by Sephadex G-200 gel filtration. The molecular weight of the denatured enzyme was found to be 155 000 by disc gel electrophoresis in the presence of sodium dodecyl sulfate. Km values of peak II and peak III fraction for Hippuryl-His Leu-OH were 2.6 mM.
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PMID:Solubilization of angiotensin I-coverting enzyme from rabbit lung using trypsin treatment. 18 21

One of several novel peptidic inhibitors of angiotensin converting enzyme (CEI) has been studied intravenously both in normal male volunteers and severely hypertensive patients without any clinically significant adversity or intolerance. Hypertensive patients experienced a significant yet gradual reduction in resting arterial pressure without hypotension. The addition of a diuretic agent was observed to potentiate this antihypertensive effect. Normal, sodium replete volunteers received this nonapeptide intravenously in doses up to 2-0 mg/kg without any significant cardiovascular effect. Both patients and normal subjects exhibited reversible dose related increases in angiotensin I and renin levels after receiving the peptide. The plasma renin response to tilting was also potentiated by CEI. These findings suggest that intravenous CEI may be of value in the treatment of severely elevated hypertension and as a tool to evaluate vasoconstrictor and volume factors in hypertension.
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PMID:Endocrine and cardiovascular consequences of angiotensin converting enzyme inhibition. 19 63

We assessed vascular and hormonal responses to inhibition of peptidyldipeptide hydrolase, which converts angiotensin I to angiotensin II (converting enzyme) and degrades bradykinin (kininase II), in subjects given 10 meq of sodium to activate both systems. In nine normal subjects a threshold dose of 30 MICROgram per kilogram of the inhibitor, SQ 20881, modestly influenced mean blood pressure (-5 +/- 1 mm Hg, P less than 0.05), and renal blood flow (+50+/-8 ml per 100 g per minute), plasma renin activity (+ 2.3 +/- 0.6 ng per milliliter per hour), and angiotensin II (-11 +/- 3 pg per milliliter) more strikingly (P less than 0.01). In six patients with essential hypertension the threshold inhibitor dose was reduced to 10 microgram per kilogram; 30 kilogram per kilogram had an enhanced (P less than 0.01) effect on mean blood pressure (-11 +/- 2 mm Hg), renal blood flow (137 +/- 20 ml per 100 g per minute), and angiotensin II concentration (-29 +/- 12 pg per milliliter). SQ 20881 elevated plasma bradykinin concentration (7.4 +/- 2.6 ng per milliliter, P less than 0.02) only in the hypertensive patients. Because both renin-angiotensin and kallikrein-bradykinin systems are influenced, vascular responses to SQ 20881 must be interpreted cautiously, but this agent has excellent antihypertensive characteristics.
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PMID:Accentuated vascular and endocrine response to SQ 20881 in hypertension. 19 3

Brattleboro rats homozygous for hypothalamic hereditary diabetes insipidus (DI rats) were used to investigate the following questions: a) Do exogenous and endogenous angiotensin II (AII) have an antidiuretic effect in diabetes insipidus? b) Does AII mediate the antidiuresis induced by furosemide? The following results were obtained: 1. AII (5 mg/kg s.c. in oil) and furosemide (50 mg/kg i.p.) decreased urine flow and increased urinary sodium excretion. Furosemide led to a two-fold increase of AII plasma concentrations and a decrease of plasma sodium levels. 2. SQ 14 225 (2 x 2.5 mg/kg p.o.), an angiotensin I-converting enzyme inhibitor, led to an increase of urine flow and to a slightly elevated urinary sodium excretion. 3. When the formation of AII was blocked by SQ 14 225 (2 x 2.5 mg/kg p.o.), AII plasma concentrations were 2.5-fold decreased, but furosemide still reduced urine flow. We conclude that plasma AII might have an antidiuretic action in DI rats. However, AII does not mediate the antidiuresis induced by furosemide.
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PMID:Inhibition of the renin-angiotensin-system in Brattleboro rats with hereditary hypothalamic diabetes insipidus. 21 21


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