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)

In hypertensive patients with bilateral renal artery stenosis (RAS) or RAS of a solitary kidney, reversible decrease of glomerular filtration rate (GFR) or acute renal failure has been observed following captopril administration. Decrease of GFR has been ascribed to preferential efferent vasodilatation. To test this hypothesis, acute changes of mean arterial pressure (MAP), renal plasma flow (RPF), GFR, plasma renin activity (PRA) and PGE2-excretion after 50 mg captopril orally were measured in post-transplant hypertensives with and without transplant renal artery stenosis (TRAS) during treatment with diuretics. The fall in MAP was similar in both groups; RPF did not change significantly; GFR decreased from 58 +/- 14 (s.d.) to 49 +/- 14 ml/min (TRAS, n = 8) and from 60 +/- 15 to 50 +/- 16 ml/min (without TRAS, n = 8). There was no evidence of postglomerular dilatation in patients with TRAS, and filtration fraction decreased only in patients without TRAS. Increase of PRA after captopril was not significantly different between the two groups. PGE2-excretion did not change significantly. In one patient with severe TRAS, long term angiotensin converting enzyme (ACE) inhibition and acute normalization of MAP with sodium nitroprusside both induced a comparable decrease of GFR. The results demonstrate that acute postglomerular vasodilatation does not necessarily occur after ACE inhibition in patients with TRAS and a high-renin state.
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PMID:Does captopril reduce renal function in renovascular disease by postglomerular vasodilatation? 391 Jul 70

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

Renal extraction and renal plasma clearance of atrial natriuretic peptide from pigs with complete unilateral ureteral obstruction (UUO) and from intact anaesthetized pigs were determined from arteriovenous differences in plasma atrial natriuretic peptide and measured renal plasma flow. The effect of administration of either a cyclooxygenase inhibitor or an angiotensin converting enzyme inhibitor was examined during UUO. Renal extraction ratio and renal clearance rate of plasma atrial natriuretic peptide (ANP) in the intact pig was stable during the 15 h observation period. UUO resulted in a significant (P < 0.05) temporary increase in renal extraction ratio and a significant (P < 0.05) reduction in the renal clearance rate of atrial natriuretic peptide. During cyclooxygenase inhibition there was a significant increase in the renal extraction ratio of ANP. During angiotensin II converting enzyme inhibition, renal handling of atrial natriuretic peptide did not differ from that observed in control animals. The present data demonstrate that atrial natriuretic peptide is extracted by the obstructed kidney. Despite the significant reduction in renal blood flow during indomethacin administration, renal clearance of ANP was unaltered. The increase in ipsilateral renal extraction of atrial natriuretic peptide immediately after ureteral obstruction and indomethacin administration could be explained either by a direct influence of PGE2 on the renal haemodynamics altering renal extraction of ANP, or by a compensatory mechanism attempting to preserve renal function.
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PMID:Renal clearance of atrial natriuretic peptide during acute unilateral complete ureteral obstruction in the pig. 760 Dec

Greater protein intake increases glomerular eicosanoid production in rats. Bilateral ureteral obstruction (BUO) also enhances glomerular eicosanoid production in experimental animals. To examine the effects of dietary protein intake on glomerular eicosanoid production in ureteral obstruction, we measured the in vitro production of the vasodilatory prostaglandins, PGE2, and 6-keto PGF1 alpha, and the vasoconstrictor, TxB2, and the mass of cyclooxygenase in glomeruli of sham-operated control (SOC) rats and rats with BUO of 24 hr duration fed a low- (6% casein) or a high- (40% casein) protein diet for approximately 4 weeks. The animals were pretreated or not with the angiotensin converting enzyme inhibitor, enalaprilat, prior to sham-operation or ureteral obstruction. Glomeruli from SOC rats fed a high-protein diet produced significantly greater amounts of PGE2, 6-keto PGF1 alpha, and TxB2, and had substantially increased mass of cyclooxygenase when compared with glomeruli from SOC rats fed a low-protein diet. Pretreatment of animals with enalaprilat prior to sham operation prevented the increase in glomerular eicosanoid production and cyclooxygenase content in SOC rats fed a high-protein diet and the levels observed were similar to those in SOC rats fed a low-protein diet. Both eicosanoid production and cyclooxygenase mass were further increased in glomeruli from rats with BUO fed a high-protein diet when compared with glomeruli of SOC rats fed the same diet. The increased levels of these measurements in BUO rats fed a high-protein diet fell markedly when the rats were pretreated with enalaprilat in vivo. The values were essentially comparable to those of SOC rats fed a low-protein diet. By contrast, there was no substantial increase in the production of PGE2, 6-keto PGF1 alpha, and TxB2 and in the mass of cycloxygenase in glomeruli of BUO versus SOC rats fed a low-protein diet. Enalaprilat did not affect glomerular eicosanoid production or cyclooxygenase content in SOC and BUO rats fed a low-protein diet. Taken together, the present study indicates that dietary protein affects BUO-induced increases in glomerular eicosanoid production by altering the activity of the cyclooxygenase pathway mainly via the reninangiotensin system. Thus, protein content in a diet may modify an alteration in renal hemodynamics caused by BUO by changing the glomerular production of eicosanoids and the activity of the renin-angiotensin system.
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PMID:Effects of dietary protein on glomerular eicosanoid production in rats with bilateral ureteral obstruction. 793 55

The influential studies by Hostetter and associates [103] as well as by others in the last decade have firmly established the association between adaptive increases in renal hemodynamics as well as tubular reabsorption and the progression of renal disease. Many different vasoactive hormones may be involved in such regulatory processes. On the other hand, many investigators have observed that compensatory renal growth, although initially helping to restore functional renal tissue, may be rather harmful in the long-term for renal function, even in the absence of concomitant hemodynamic changes. These apparently separate areas of renal pathophysiology have become united by the identification of the growth regulatory properties of many vasoactive substances. Thus, a perturbation of vasoconstrictors and vasodilatory substances may not only influence vascular tone, glomerular filtration rate and renal plasma flow but also the growth regulation of distinct populations of cells along the nephron. As a generalization, it appears that vasoconstrictors stimulate growth of renal cells (mitogenesis and hypertrophy), whereas vasodilators inhibit the growth response. It can be speculated that similar effects of different hormones may depend on the activation of common second messenger pathway, e.g. the ANG-II-, AVP-, ET-induced mesangial proliferation through the phosphorylation of a common set of target proteins, or the antimitogenic effects of ANP, EDRF and PGE2 through an increase in intracellular cGMP. However, the majority of the growth regulatory effects of vasoactive substances have been studied in relatively artificial cell culture systems. Nevertheless, the well-documented protective effects of ACE inhibitors on renal function in several models include effects on renal growth. The rapid development of new vasoactive drugs like the recently introduced nonpeptide ANG II receptor antagonists may also offer an opportunity to influence renal growth [104]. The mechanisms of the progression of renal disease have become fascinatingly complex, and the next years will most likely witness major achievements in the elucidation of chronic renal pathophysiology on both cellular and molecular levels.
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PMID:Vasoactive substances as regulators of renal growth. 808 63

Studies were performed to determine whether the inhibition of the decidual cell reaction induced by intrauterine infusion of the angiotensin converting enzyme inhibitor enalaprilat in rats is reversed by activation of Ca2+ influx. Influx of Ca2+ was shown to be stimulated by angiotensin II in endometrial cells in this study. Ovariectomized, adult female rats were sensitized for the decidual cell reaction with steroid treatments. For experiments in vivo, intrauterine infusions of enalaprilat alone, or in combination with the Ca2+ ionophore A23187, a synthetic diacylglycerol, and dioctanoyl-sn-glycerol (diC8), and PGE2 were initiated on the day of uterine sensitivity. Enalaprilat inhibited the increases in uterine PG concentrations and uterine weight that occur following infusion of the vehicle. Concurrent infusion of A23187 partially, but not completely, reversed the inhibition of uterine weight increase; diC8 did not affect the inhibition of enalaprilat. A23187 did not reverse the effects of enalaprilat on uterine PG concentrations. Concurrent infusion of A23187 and PGE2 fully reversed the inhibitory effect of enalaprilat on uterine weight. For experiments in vitro, endometrial stromal and epithelial cells were obtained from uteri on the day of sensitivity and maintained in suspension. Cytosolic free calcium concentration ([Ca2+]i) was monitored in cell suspensions by fluorescence spectrophotometry using the Ca(2+)-sensitive probe, indo-1. Angiotensin II induced a transient increase in [Ca2+]i of endometrial stromal cell suspensions, but not of epithelial cells; PGE2 did not increase [Ca2+]i in stromal or epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Requirement for Ca2+ mobilization and increased prostaglandin production for maximal decidualization in rats and the involvement of angiotensin II. 841 Aug 7

The effects of the diuretic furosemide (CAS 54-31-9) 1 mg/kg bw i.v., of the angiotensin converting enzyme (ACE) inhibitor captopril (CAS 62571-86-2) 1 mg/kg bw p.o. and the prostaglandin synthesis inhibitor indometacin (CAS 53-86-1) 2 mg/kg bw p.o. on kidney function, salt and water excretion, the excretion of renal prostaglandins PGE2, PGF2a, 6-keto-PGF1a, thromboxane B2 (TXB2) and the plasma renin activity (PRA) were investigated on 29 neonatal piglets. Within 1 h, fuorsemide led to pronounced diuresis and natriuresis, to a rise of the glomerular filtration rate (GFR) (which ist low in neonatal pigs) by 1.8 times, increased the excretion of renal prostaglandins (especially the vasoconstrictor, thromboxane B2 (TXB2 and PGF2a) and raised the PRA significantly. Under captopril, the PRA rose significantly, whereas there was no unequivocal change in the excretion of renal prostaglandins. There was a pronounced decline of the sodium and potassium excretion in the urine with a fall in the concentrations of electrolytes in serum and of the hematocrit. Under indometacin, the excretion of all prostaglandins in the urine declined (this decline was most pronounced for PGE2). There was also a decrease in sodium excretion, whereas there was no significant change in PRA. It can be concluded from the results that the effects of the investigated drugs on the pig neonate kidney is at least partially attributable to an influence on hormonal factors.
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PMID:Effects of furosemide, captopril and indometacin on the renin-angiotensin system and the renal prostaglandins in anesthetized neonatal piglets. 857 31

The efficacy of angiotensin converting enzyme inhibitors in the treatment of heart disease is due in part to the accumulation of bradykinin (BK). Since BK can exert its effect by influencing cell proliferation, we chose to study the effect of BK on the growth of A10 vascular smooth muscle cells. Ligand binding studies to determine which BK receptor subtypes are present on A10 cells showed that both B1 and B2 receptors were present in approximately equal numbers. Examination of RNA synthesis demonstrated that BK inhibits uridine incorporation in a dose-dependent manner. This decrease in RNA synthesis was blocked by both B1 and B2 receptor antagonists, as well as by addition of indomethacin, a cyclooxygenase inhibitor. The latter result suggested that prostaglandins mediate the biological actions of BK. Consequently, we examined the direct effect of two prostaglandins, PGE2 and PGI2 (prostacyclin), on A10 cells. PGE2 caused a decrease in RNA synthesis, thus mimicking the effect of BK, while PGI2 did not. Therefore, the inhibition of RNA synthesis in A10 vascular smooth muscle cells by BK requires both B1 and B2 receptor subtypes and this action of BK is apparently mediated by de novo synthesis of prostaglandins.
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PMID:Inhibition of RNA synthesis by bradykinin involves both the B1 and B2 receptor subtypes. 863 19

We have investigated the modulatory effect of dietary perilla oil which is rich in the n-3 polyunsaturated fatty acid, alpha-linolenic acid, on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in male F344 rats. Animals were given three weekly subcutaneous injections of AOM (15 mg/kg body weight) to induce ACE. The rats were fed a basal diet containing either 12% olive oil, 12% safflower oil, 12% perilla oil, 6% perilla oil plus 6% olive oil, or 3% perilla oil plus 9% olive oil for 5 weeks, starting 1 week before the first dosing of AOM. All rats were sacrificed 2 weeks after the last AOM injection. The amount of food consumed and body weight gain were identical among every dietary group. The frequency of ACF was significantly lower in the rats fed 12% perilla oil than in those fed 12% olive oil or 12% safflower oil (P < 0.01 and P < 0.05, respectively). The suppressive effect of perilla oil was dose-dependent, as the number of ACF was 20.7, 40.7 and 47.4% of those of the 12% olive oil-fed controls in rats fed 12% perilla oil, 6% perilla oil plus 6% olive oil and 3% perilla oil plus 9% olive oil, respectively. Perilla oil significantly reduced ras expression as well as the AgNORs count (cell proliferation biomarkers) in the colonic mucosa, as compared with olive oil or safflower oil (P < 0.01, respectively). Marked increases in n-3 polyunsaturated fatty acids in membrane phospholipid fractions and decreased PGE2 levels were observed in colonic mucosa of perilla oil-fed rats. These results suggest that perilla oil, even in small amounts, suppresses the development of aberrant crypt foci, and is therefore a possible preventive agent in the early stage of colon carcinogenesis.
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PMID:Suppressing effect of perilla oil on azoxymethane-induced foci of colonic aberrant crypts in rats. 868 45

1. The effect of pretreatment with bacterial endotoxin (LPS, 10 micrograms, i.v., 24 h) on the bradykinin B1 and B2 receptor-induced oedema in the rat paw, and the interaction of B1-mediated responses with other inflammatory mediators, was investigated. 2. Intraplantar (i.pl.) injection of the selective B1 agonist, des-Arg9-BK (DABK, 100 nmol) in naive animals pretreated with the angiotensin converting enzyme inhibitor, captopril caused a small increase in paw volume (0.04 +/- 0.003 ml, mean +/- s.e. mean, n = 6), while the B2-selective agonist, tyrosine8-bradykinin (T-BK, 3 nmol) induced marked oedema (0.36 +/- 0.02 ml). However, i.pl. injection of DABK (3-300 nmol) in rats pretreated with LPS (24 h beforehand) resulted in a marked dose- and time-related increase in paw volume, with mean ED50 of 24.1 nmol. In contrast, oedema caused by T-BK (3 nmol) was reduced by 79 +/- 4% in animals treated with LPS when compared with naive animals. 3. Oedema caused by prostaglandin E2 (PGE2, 10 nmol) was unaffected by LPS treatment, while oedema induced by histamine (100 nmol), 5-hydroxytryptamine (5-HT, 10 nmol) and substance P (SP, 3 nmol) was reduced (P < 0.05). 4. The selective B1 antagonist, des-Arg9[Leu8]-BK (100-300 nmol), produced dose-dependent inhibition of DABK (100 nmol)-induced paw oedema in LPS-treated animals with mean IC50 of 134 nmol, while the selective B2 antagonists, Hoe 140 and NPC 17731 (each 10 nmol), had no effect. 5. Treatment of animals with dexamethasone (0.5 mg kg-1, s.c.) 24 or 48 h prior to LPS injection resulted in a graded inhibition of DABK (100 nmol)-induced oedema formation (58 +/- 3 and 82 +/- 2%, respectively), and almost reversed to control value oedema formation induced by T-BK (3 nmol) in LPS-pretreated rats. Cycloheximide (1 mg kg-1, s.c.) or indomethacin (2 mg kg-1, i.p.) pretreatment 24 and 1 h prior to LPS injection, respectively, markedly inhibited DABK (100 nmol)-induced paw oedema (98 +/- 2 and 50 +/- 4%, respectively). 6. Intraplantar injection of submaximal dose of DABK (10 nmol) in LPS-treated rats produced modest paw oedema (0.09 +/- 0.03 ml). However, i.pl. injections of PGE2, prostacyclin (PGI2), calcitonin-gene-related peptide (CGRP), SP, 5-HT, or platelet activating factor (PAF) (each 1 nmol), which alone caused little or no paw oedema, resulted in a potentiation of the DABK-induced oedema. The increases in paw volume (in ml) were: PGE2 + DABK (0.31 +/- 0.03), PGI2 + DABK (0.39 +/- 0.02), CGRP+DABK (0.35 +/- 0.04), DABK+SP (0.33 +/- 0.04), DABK + 5-HT (0.40 +/- 0.02) and DABK+PAF (0.38 +/- 0.016) ml. In contrast, histamine (1 nmol) was ineffective in potentiating the response to DABK. 7. The selective B1 receptor antagonist, DALBK (100-300 nmol), produced dose-dependent inhibition of paw oedema potentiation induced by co-injection of DABK and other mediators with mean ID50S (nmol) of: 180, 160, 139 and 135 in the presence of PGE2, PGI2, SP and 5-HT, respectively. 8. These results demonstrate that DABK-induced increase in paw volume in LPS-treated rats is probably mediated by induction of B1 receptors, associated with downregulation of B2 receptors. The induction of B1 receptors by LPS is sensitive to dexamethasone and cycloheximide treatment and requires activation of cyclo-oxygenase pathway. In addition, B1 receptors, when upregulated following LPS treatment, can interact in a synergistic manner with several inflammatory mediators such as PGI2, PGE2, CGRP, PAF and 5-HT. Such results indicate that induction of the B1 receptor might have a significant pathophysiological role in modulating chronic inflammatory diseases.
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PMID:Upregulation of B1 receptor mediating des-Arg9-BK-induced rat paw oedema by systemic treatment with bacterial endotoxin. 885 92


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