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)

Bartter's syndrome (B.S) is often difficult to distinguish from pseudo-Bartter's syndrome (pseudo-B.S), a condition which may be caused by "loop" diuretics abuse. Although our patient firmly denied ingestion of diuretics or laxatives, all screening of urine samples gave consistently positive results for furosemide, even during hospitalization. A 25-year-old married woman with persistent hypokalemia had many characteristics of B.S, including hypokalemic hypochloremic alkalosis, hyperactivity of the renin-angiotensin-aldosterone system, normotension, insensitivity to the pressor effect of angiotensin II (A.II), increased urinary excretion of prostaglandin E2 and kallikrein, and marked reduction of distal fractional reabsorption of chloride in Henle's loop, as estimated by CH2O/CH2O+C.Cl, under conditions of hypotonic saline diuresis. Furthermore, hypotension occurred with [1-Sar, 8-Ile] A.II and with the angiotensin converting enzyme inhibitor (Captopril). Renal biopsy revealed juxtaglomerular hyperplasia. A tentative diagnosis of B.S was made. Indomethacin (IDM), an inhibitor of prostaglandin synthesis was prescribed and the pressor response to A.II improved. Impaired fractional chloride reabsorption was also improved significantly under IDM, but the value was low compared to the normal. The value for basal plasma human atrial natriuretic polypeptide (hANP) was slightly above the normal ranges and was suppressed by IDM. We conclude that manifestations B.S in this patient may have been fostered significantly by the long-term surreptitious use of furosemide, taken to lose weight. The analysis of urine for detection of diuretics was only finding distinguishing her clinical state from "true" B.S and leading to a final diagnosis. Pathophysiologic relationships between B.S and pseudo-B.S due to furosemide are discussed.
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PMID:[Pseudo-Bartter's syndrome induced by surreptitious ingestion of furosemide to lose weight: a case report and possible pathophysiology]. 302 52

We evaluated the influence of indomethacin on the pharmacological actions of Enalapril in 9 uncomplicated essential hypertensives. While on chronic treatment with Enalapril, these patients randomly received indomethacin (50 mg bid) or a corresponding placebo for 1 week and the opposite treatment after a 2 week interval. Indomethacin, which decreased serum thromboxane B2 and urinary 6-keto prostaglandin-F1 alpha, reduced the plasma renin activity (PRA) increased by Enalapril. Indomethacin did not modify serum ACE, whose activity had been reduced by the ACE inhibitor. Mean blood pressure (MBP) values, which were significantly and to a similar extent reduced by Enalapril at the beginning of the cross-over, after placebo addition and at the end of the two week interval, were significantly increased by indomethacin, despite being still significantly lower than baseline values. These data show that systemic and renal prostaglandin (PG) synthesis inhibition induced by indomethacin can blunt the antihypertensive effect of chronic Enalapril treatment in patients with essential hypertension.
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PMID:Indomethacin reduces the antihypertensive action of enalapril. 303 18

We investigated the effect of captopril, an orally active angiotensin converting enzyme inhibitor, on urinary protein excretion in puromycin aminonucleoside nephrotic rats. The administration of captopril (10 mg/100 g body weight) decreased proteinuria on days 10-14 following the administration of puromycin aminonucleoside (73.0 versus 125.0 mg, p less than 0.01), without affecting glomerular filtration rate. The beneficial effect of captopril was not abolished by the continuous intravenous infusion of angiotensin II (10 micrograms/kg/h for 9 days) or subcutaneous injections of aprotinin (50,000 KIU/day for 3 days). Indomethacin, in moderate (5 mg/kg/day for 3 days) or high (10 mg/kg/day) doses, abolished the captopril attenuation in urinary protein excretion. The salutory effect of captopril was characterized by a reduction in the fractional excretion of protein without compromising the glomerular filtration rate. No difference in renal ultrastructure was noted in captopril-treated versus control animals. Captopril was ineffective in reducing urinary protein excretion in rats with adriamycin-induced glomerulopathy. We conclude that captopril acts to reduce proteinuria in renal disease states arising from depletion of the glomerular basement membrane polyanion. The mechanism of action is postulated to be an alteration in renal hemodynamics, namely increased blood flow and a decrease in the ultrafiltration coefficient, that are the consequence of increased intrarenal prostaglandin production.
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PMID:The effect of captopril on urinary protein excretion in puromycin aminonucleoside nephrosis in rats. 389 1

In order to evaluate the participation of prostaglandins and bradykinin in autoregulation of renal blood flow, the pressure-flow relationships were examined before and during the infusion of prostaglandin E2, sodium arachidonate or bradykinin in the pump-perfused kidney of anesthetized dogs. Renal arterial pressure was changed in a step-wise fashion between 60 and 200 mmHg by means of a pneumatic resistance. Renal blood flow revealed an effective autoregulation against the pressure changes between 100 and 200 mmHg. Infusion of prostaglandin E2 (30 and 100 ng/min), sodium arachidonate (200 and 500 micrograms/min) or bradykinin (100 and 300 ng/min) into the renal artery increased renal blood flow dose-dependently, but had no influence on the autoregulation of renal blood flow. We also examined the effect of endogenous bradykinin and prostaglandins by the intravenous administration of captopril (1 mg/kg), a kininase II inhibitor, and indomethacin (2.5 mg/kg), a cyclo-oxygenase inhibitor, respectively. Captopril increased renal blood flow, but did not impair the autoregulation. Indomethacin decreased renal blood flow and had no effect on the renal autoregulation. It is considered that prostaglandins and bradykinin which induced renal vasodilation have no role in the autoregulation of renal blood flow in the dog kidney.
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PMID:No role for prostaglandins and bradykinin in the autoregulation of renal blood flow. 393 25

The effects of three angiotensin converting enzyme (ACE) inhibitors - captopril, MK-421 diacid, and teprotide - on renal vascular responses to graded (50, 100, 200 ng) injections of norepinephrine (NE) were examined in rat isolated perfused kidneys, having a mean basal perfusion pressure of 78 +/- 10 mm Hg. The minimum dose of captopril (0.05 microgram/ml, low dose) that abolished the vasoconstrictor responses to 100 and 200 ng angiotensin I did not affect NE-induced renal vasoconstriction, whereas a dose 100 times greater (high-dose captopril, 5 micrograms/ml) reduced the vasoconstrictor action of NE. MK-421 diacid also at high dose (1 microgram/ml), caused similar reduction in renal vasoconstrictor responses to NE. In contrast, a high dose of teprotide (50 micrograms/ml) did not affect renal vascular responsiveness to NE. The threshold dose of NE that released prostaglandins, measured by bioassay, was 50 ng. Indomethacin (1 microgram/ml) prevented NE-induced release of prostaglandins but did not affect the ability of captopril to attenuate NE-induced vasoconstriction. We conclude that captopril and MK-421 diacid decreases vascular reactivity in the rat isolated kidney by a mechanism independent of ACE inhibition and unrelated to a prostaglandin-dependent vascular mechanism. Moreover, the presence of mercapto function in the ACE inhibitor is not essential since captopril, which has a sulfhydryl group, and MK-421 diacid, which lacks this group, have similar effects on renal vascular responsiveness.
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PMID:Decreased vascular responsiveness produced by angiotensin-converting enzyme inhibitors in the rat isolated kidney. 617 73

The relationship of the vascular effect of captopril to angiotensin converting enzyme activity and prostaglandin-dependent mechanism was studied in rat isolated kidneys, perfused with Krebs-Henseleit at 20 ml/min per 2 kidneys, with basal perfusion pressures of 78 +/- 1 mm Hg (Mean +/- S.E.M.). Two doses of captopril were used; both low (0.05 microgram/ml) and high doses (5 microgram/ml) inhibited maximally the vasoconstrictor responses to 100 and 200 ng of angiotensin I. Captopril at the low dose did not affect the renal vasoconstrictor responses to norepinephrine (NE) (25-400 ng), whereas high-dose reduced the vasoconstriction to all doses of NE. Treatment with captopril tended to diminish dose-related release of prostaglandins in response to NE. Indomethacin (1 microgram/ml) prevented NE-induced release of bioassayable and radioimmunoassayable prostaglandins but did not affect the ability of captopril to reduce NE-induced vasoconstriction. High-dose captopril also decreased the vascular reactivity to angiotensin II (5 ng) and lysine vasopressin (10 mU); however, the renal vasoconstriction caused by PGE2 (80 ng) was unaffected by captopril. We conclude that high-dose captopril decreased vascular reactivity by a mechanism independent of converting enzyme inhibition and unrelated to a prostaglandin-dependent vascular mechanism.
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PMID:Captopril decreases vascular reactivity independently of changes in converting enzyme activity and prostaglandin release in the rat isolated kidney. 629 42

Cyclic analogs of bradykinin (CBK) and kallidin (CK) have a weak myotropic activity and a marked and prolonged hypotensive effect unlike linear bradykinin (BK) and kallidin (K) which produce a short-term hypotension and considerable contraction of rat uterus smooth muscles. Myotropic effects of BK and CK were significantly inhibited by phentolamine, methysergide, papaverine and verapamil. Atropine, diphenhydramine and propranolol have no influence on the kinin-induced myotropic responses. The prolonged decrease in blood pressure induced by CBK and CK is observed in un- and anesthetized normotensive, spontaneously hypertensive rats and rats with renovascular hypertension and is absent from anesthetized cats and guinea-pigs. This indicates the species specificity of cyclokinins. Indomethacin, diphenhydramine and methysergide failed to influence the BK- and CK-induced hypotensive effects on anesthetized rats. CaCl2 did not influence the magnitude of the hypotensive effect of BK and CK, however, it significantly shortened the duration of the CK-induced hypotensive effect. In vitro CBK and CK inhibited activity of kininase II in a similar manner (at a concentration range of 10(-5) M) but to a less extent than BK (10(-7)-10(-6) M). It is suggested that the hypotensive effect of CK is mediated at least partly via Ca2+-dependent systems and inhibition of kininase II.
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PMID:[Mechanism of action of cyclokinins]. 631 9

The circulatory effects of captopril, an angiotensin I-converting enzyme inhibitor, and saralasin, a competitive angiotensin II antagonist, were studied during halothane anaesthesia in spontaneously hypertensive (SH) rats. Captopril decreased blood pressure significantly in unanaesthetized rats. Pretreatment with indomethacin, a prostaglandin synthesis inhibitor, did not modify the antihypertensive action of captopril. During 1 MAC halothane anaesthesia, the mean arterial pressure (MAP) in unmedicated SH control rats was maintained at a relatively high level (16.2 +/- 0.7 kPa, mean +/- s.e. mean), while in captopril-treated rats MAP decreased to 8.8 +/- 1.1 kPa. Indomethacin somewhat inhibited MAP decrease in the captopril-medicated group. Saralasin infusion in halothane-anaesthetized rats decreased MAP in the same way as captopril alone. The tolerance to haemorrhagic shock was markedly impaired in rats receiving captopril or saralasin, compared to untreated controls. During halothane anaesthesia, the plasma renin activities in the captopril, captopril + indomethacin, and saralasin groups were significantly higher than in untreated animals. Plasma kininogen was unaffected by any of the medications. The results suggest that the renin-angiotensin system is important in maintaining blood pressure in halothane anaesthesia, and that the tolerance to haemorrhagic shock is particularly impaired by drugs inhibiting the renin-angiotensin system.
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PMID:Circulatory effects of renin-angiotensin system antagonists during halothane anaesthesia in hypertensive rats. 634 Apr 6

Previous studies in adult animals have indicated that plasma angiotensin converting enzyme (ACE) activity is inhibited by endotoxin. Reduced ACE activity may decrease plasma angiotensin II (AII) levels, contributing to the refractory hypotension we have previously reported in neonatal septic shock. In this study, hemodynamic function, plasma renin activity (PRA), AII, prostacyclin (PGI2), and thromboxane B2 (TxB2) levels were measured in 17-20-day-old dogs before and 1, 2, and 3 hr after endotoxin administration (1 mg/kg, Escherichia coli lipopolysaccharide-B). PRA and AII levels rose significantly 60 min post-endotoxin, returning to baseline values by 180 min; PGI2 and thromboxane B2 levels rose post-endotoxin and remained elevated. Indomethacin or captopril was given by oral gavage 30-35 min before endotoxin. Captopril significantly blunted the rise in PRA and AII, while indomethacin blocked the rise in PGI2 and TxB2. Mean arterial blood pressure and cardiac output fell 60 min after endotoxin challenge without pharmacologic intervention and remained depressed. Our data suggest that renin and AII responses to endotoxin challenge remain intact in the neonatal subject. Maintenance of hemodynamics in indomethacin-pretreated dogs may be due to unopposed stimulation of the peripheral vasculature by AII. Thromboxane B2 in maintenance of vasomotor tone may be minimal in the young.
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PMID:Role of angiotensin II in neonatal sepsis. 850 19

1. Substance P (SP) and capsaicin induced a mechanical hyperalgesia when injected into rat knee joints. 2. The NK1 receptor antagonists CP 99994 (10-100 nmol) and RP 67580 (0.1-1 nmol) blocked the development of, and also reversed, SP-induced hyperalgesia. Capsaicin (10 nmol)-induced hyperalgesia was blocked by capsazepine (0.5-5 nmol). 3. Capsaicin-induced hyperalgesia was prevented and reversed by the NK1 receptor antagonists CP 99994 (100 nmol) and RP 67580 (1 nmol). 4. The bradykinin B2 receptor antagonist icatibant (5 pmol) blocked the development of both SP and capsaicin-induced hyperalgesia. Icatibant (100 pmol kg-1, i.v.) also reversed an established SP and capsaicin-induced hyperalgesia. 5. Both low dose SP (1 nmol) and capsaicin (1 nmol)-induced hyperalgesia were potentiated by the kininase II inhibitor captopril (100 micrograms). 6. The B1 receptor antagonists desArg9Leu8-bradykinin (BK) (0.5-5 nmol) and desArg10[Hoe 140] (5-50 pmol) only blocked the development of SP-induced hyperalgesia for 30 min after administration. desArg9Leu8-BK (10 nmol kg-1 i.v.) did not reverse an established SP-induced hyperalgesia. 7. Capsaicin-induced hyperalgesia was blocked by desArg9Leu8-BK (0.5 nmol) and this antagonist also reversed an established capsaicin-induced hyperalgesia. 8. Interleukin-1 receptor antagonist (IL-1ra 0.1 microgram) reduced the development of SP-induced hyperalgesia up to 4 h after administration, but did not reverse an established hyperalgesia. IL-1ra (0.1 microgram) also blocked the development of and reversed an established capsaicin-induced hyperalgesia. 9. Indomethacin pretreatment (1 mg kg-1, s.c.) did not reduce the development of either SP- or capsaicin-induced hyperalgesia but following indomethacin-pretreatment desArg9Leu8-BK (10 nmol kg-1, i.v.) failed to reverse a capsaicin-induced hyperalgesia. 10. In conclusion, both SP and capsaicin can induce behavioural hyperalgesia when injected into the knee joint of rats. In addition, blockade of NK1, bradykinin B1, B2 and IL-1 beta receptors can substantially modulate this hyperalgesia.
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PMID:Substance P and capsaicin-induced mechanical hyperalgesia in the rat knee joint; the involvement of bradykinin B1 and B2 receptors. 886 63


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