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)

Results from animal experiments have suggested that treatment with recombinant human erythropoietin (rHuEPO) causes changes in renal hemodynamics which are detrimental to renal function. Therefore, the effects of correction of the anemia by rHuEPO on glomerular filtration rate (GFR; inulin clearance) and effective renal plasma flow (ERPF; PAH clearance) were studied in eight pre-dialysis patients. The studies were done before (Hct 0.24 +/- 0.05 liter/liter) and at 89 +/- 19 days after the start of rHuEPO therapy (Hct 0.39 +/- 0.03 liter/liter). To further evaluate the effects of ACE inhibition, 25 mg of captopril was given orally after baseline values had been obtained. Baseline GFR, renal blood flow (RBF) and filtration fraction (FF) did not change during rHuEPO therapy. At low hematocrit (Hct) captopril induced a significant increase in ERPF and RBF, and a decrease in MAP. After correction of the hematocrit the blood pressure lowering effect of captopril remained unchanged. However, captopril no longer induced changes in ERPF and RBF. We conclude that the increase in hematocrit had no adverse effects on GFR. The results suggest that changes in hematocrit may influence the effects of ACE inhibition on efferent vascular resistance. Therefore, the hematocrit should be taken into account when evaluating studies on the effects of ACE inhibition in the progression of chronic renal failure.
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PMID:Evidence for renal vasodilation in pre-dialysis patients during correction of anemia by erythropoietin. 155 11

Evidence is presented implicating the renin-angiotensin system in the regulation of plasma erythropoietin concentration. Male and female rats were exposed to hypoxia at 0.43 atm for 8 hr. In male rats, individual erythropoietin values showed a positive correlation with renin, renin substrate, and angiotensin I after 8 hr of hypoxia. In female rats, renin was not elevated during hypoxia. However, after renin was injected subcutaneously, plasma renin values became similar to those in male rats and erythropoietin doubled. Individual erythropoietin values of the combined groups showed a positive correlation with plasma renin. A single oral dose of SQ 14225, an angiotensin I-converting enzyme inhibitor, reduced erythropoietin to undetectable levels in renin-injected female rats. Angiotensin II, in subpressor amounts, prevented the suppression of erythropoietin by SQ 14225. SQ 14225 also reduced renin substrate concentration at ambient pressure and during hypoxic exposure. The correlation coefficient between renin substrate and erythropoietin in rats given SQ 14225 to lower substrate or angiotensin II to increase substrate was 0.85; p < 0.0005. The increase in renin substrate that occurred during hypoxia in female rats given angiotensin II correlated positively with erythropoietin, r = 0.86; p < 0.0005.
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PMID:Interrelation of the renin system and erythropoietin in rats. 699 41

Treatment of hypertension with an angiotensin converting enzyme inhibitor (ACEI) may be associated with a decrease in haemoglobin concentration especially in patients with renal insufficiency. This open study in 19 patients with a variety of renal diseases with complicating hypertension investigated the effects of the ACEI, enalapril, on haemoglobin and plasma erythropoietin (EPO) concentrations. Blood samples were obtained at baseline and 2, 60 and 120 days after starting treatment with enalapril. By day 60 there was a significant decrease in mean haemoglobin concentration (mean decrease 7.4 g/l) that was sustained until day 120. Apart from a small, but significant, reduction by day 2, mean plasma EPO concentration remained constant throughout the study. The magnitude of the decrease in haemoglobin concentration was, however, significantly correlated with the baseline plasma creatinine concentration and creatinine clearance. These results suggested that the degree of renal insufficiency was important in determining the haematological response to ACE inhibition. While the mechanism of these changes remains unclear, our findings suggest that inhibition of the renin-angiotensin system, rather than decreasing EPO production, may reduce the erythropoietic activity of the hormone.
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PMID:Effect of enalapril on erythrocytosis in hypertensive patients with renal disease. 749 63

Renovascular hypertension (RVH) remains a leading cause of potentially curable hypertension. Although RVH affects less than 1% of the unselected hypertensive population, between 10% and 35% of appropriately screened patients referred to specialised centres for problematic hypertension may prove to have renovascular disease. Advances in percutaneous transluminal renal angioplasty (PTRA) have renewed interest in developing better noninvasive screening tests for identifying patients with potentially correctable hypertension or renal impairment due to renovascular disease caused by either fibromuscular dysplasia (FMD) or arteriosclerosis. Duplex ultrasound with the two-dimensional Echo-Colour-Doppler technique for measurements of blood flow velocities in the renal interlobar arteries as expressed in the Pulsatility Index (PI) has been evaluated. Experimentally induced changes in renovascular resistance (RVR) in normotensives and in primary hypertensives were registered noninvasively by means of PI-measurements. A significant correlation between the absolute values of PI and RVR was found in hypertensives (r = 0.50, p < 0.002), but not in normotensives. In both groups, the changes of RVR due to angiotensin II infusion and ACE-inhibition were significantly correlated to the changes in PI (normotensives: r = 0.69, p < 0.001, primary hypertensives: r = 0.64, p < 0.001). Normally, the blood flow velocities as expressed by the PI in the renal vasculature of the two kidneys are equal. In hypertensive patients, PI was lower in kidneys with significant renal artery stenosis (RAS) than in kidneys without RAS (p < 0.001). Doppler signals were absent in all kidneys with renal artery occlusion. A bilateral low PI combined with normal side difference in PI may in hypertensive patients indicate bilateral RAS. RVH was correctly diagnosed in 84% of the patients and the presence of RAS in 94%. Provocative testing of an activated renin-angiotensin system by means of an angiotensin converting enzyme inhibitor (ACEI) constitutes the foundation for screening for RVH using gamma camera renography with 99mTc-DTPA as a glomerular filtration marker. In 20 consecutive patients with successfully treated RVH, one-third of the patients were not correctly diagnosed using ACEI-enhanced 99mTc-DTPA gamma camera renography, which indicates that some patients with RVH have compensatory mechanisms to maintain GFR after ACE inhibition. The relationship between the renin-angiotensin system and erythropoietin (EPO) production was studied in 20 patients with RAS and hypertension.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Renovascular hypertension. New diagnostic and therapeutic procedures. 766 14

Enalapril effectively decreases hematocrits in patients with postrenal transplant erythrocytosis (PTE). We studied the effect of enalapril withdrawal on erythropoiesis in 18 patients with PTE who had been treated for 13 +/- 8 months. Hematocrit, reticulocyte count, plasma erythropoietin, and plasma insulin-like growth factor I were measured biweekly for six weeks. Red cell mass, plasma volume, transferrin saturation, and plasma angiotensin II were measured at withdrawal and six weeks later. Hematocrit increased by at least 0.04 in 13 patients ('responders') but changed by -0.08 to 0.01 in five patients ('nonresponders'). In the responder subgroup, hematocrit increased from 0.43 +/- 0.05 to 0.51 +/- 0.05 (P < 0.001), red cell mass increased from 25.4 +/- 5.9 to 28.9 +/- 5.9 ml/kg body weight (P < 0.001), and transferrin saturation decreased from 41 +/- 16 to 27 +/- 9 percent (P < 0.01). Reticulocyte count increased two weeks after withdrawal of enalapril. Plasma volume did not change significantly. No measurement changed in the nonresponder subgroup. Plasma levels of erythropoietin, total erythroid stimulating activity, insulin-like growth factor I, and angiotensin II did not change significantly in either subgroup. Enalaprilat did not inhibit erythropoiesis in cell culture. Thus, erythropoiesis increased in 13 of 18 patients after stopping enalapril and was independent of changes in circulating concentrations of several erythropoietic factors, including erythropoietin. The pathogenesis of PTE and mechanism underlying the beneficial effect of angiotensin converting enzyme inhibition remain undetermined.
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PMID:Erythropoiesis after withdrawal of enalapril in post-transplant erythrocytosis. 785

Twenty-nine patients with unilateral renal artery stenosis or occlusion were investigated. The veno-arterial gradient (VA-gradient) of erythropoietin (EPO), haemoglobin oxygen saturation and plasma renin activity (PRA) was determined separately in each kidney before and 1 h after angiotensin converting enzyme inhibition (ACE-inhibition). The VA-gradient of EPO and of hemoglobin oxygen saturation were the same in the affected and unaffected kidney during basal conditions. During ACE-inhibition the VA-gradient of EPO disappeared on the affected side but not on the unaffected side. A fall in s-EPO after ACE inhibition was demonstrated in the renal vein on the affected side (-1.4 U l-1, p < 0.01), in the contralateral vein (-0.8 U l-1, p < 0.01) and in the aorta (-0.6 U l-1, p < 0.01). The O2-gradients were reduced on both sides after captopril, from 10.8-7.5% (p < 0.04) on the affected side and from 10.8-9.0% (p < 0.04) on the contralateral. It is suggested that the stimulated renin-angiotensin system may be important for EPO production in the affected kidney in unilateral renal disease.
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PMID:Effect of captopril on the renal veno-arterial gradient of erythropoietin and oxygen in unilateral renal artery disease. 814 Mar 97

This report reviews the features of erythropoietin (Epo) production after renal transplantation. Successful kidney transplantation leads to the correction of renal anaemia over an 8-10 week period. An early ineffective peak of serum Epo may occur when there is delayed graft function. A late peak follows the decrease in serum creatinine and this is associated with a rise in haemoglobin. Serum Epo returns to normal when the haematocrit reaches 32%. Acute early rejection causes a striking reduction in serum Epo and reticulocytosis. In some patients the haematocrit continues to increase after complete correction of anaemia, resulting in post-transplant erythrocytosis (PTE). PTE generally appears to be an idiopathic erythrocytosis independent of Epo secretion. A greater Epo sensitivity of erythroid progenitors has been suggested. Theophylline and angiotensin converting enzyme inhibitors, which attenuate Epo production, can be used to treat PTE. The second part of this report describes the possible impact of human recombinant Epo (rHuEpo) on renal transplantation. The avoidance of blood transfusion with rHuEpo should eliminate the initiation of anti-HLA sensitization in uraemic patients without previous pregnancy and prior allograft. In some but not all presensitized patients transfusion withdrawal may reduce the sensitization level. There is currently no evidence that the reversing of anaemia by rHuEpo in kidney recipients impairs early graft function. Our results suggest that treatment with rHuEpo prior to transplantation may prevent the appearance of PTE. rHuEPO will reverse anaemia in patients with a failing graft and severe anaemia with little risk of accelerating graft failure and adverse events.
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PMID:Erythropoietin and erythropoiesis in renal transplantation. 852 79

In patients at risk for chronic renal failure, early clinical interventions have been shown to prevent or delay progression of the disease. A low-protein diet is recommended when the serum creatinine is between 1.5 and 2.5 mg/dl. Benefit from protein restriction can only be achieved if energy intake is greater than 35 kcal/kg/d. To preserve skeletal muscle, correct metabolic acidosis with oral sodium bicarbonate supplementation. For hypertension control and renal protection, start ACE inhibitors when serum creatinine is less than 2 mg/dl. Correct anemia with erythropoietin to improve or maintain quality of life when the hematocrit falls below 30%. For the diabetic, ACE inhibitors and glycemic control have been shown to show the rate of renal failure.
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PMID:Kidney protection: how to prevent or delay chronic renal failure. 870 68

To delineate the pathogenesis of the reduction in hemoglobin occurring in renal transplant patients treated with angiotensin converting enzyme inhibitors (ACEI) and azathioprine (AZA) a controlled, prospective trial of ACEI withdrawal was conducted. The ACEI was replaced by nifedipine or clonidine in 15 kidney transplant patients immunosuppressed with AZA and prednisone (enalapril in 14 and captopril in 1). Before and during 10 to 12 weeks after withdrawal of the ACEI, AZA metabolites, renal function parameters and hematological parameters including erythropoietin and reticulocytes were evaluated. Enalaprilat levels were measured and compared with 15 similar patients matched for transplant function and enalapril dosage immunosuppressed with cyclosporine and prednisone. AZA metabolites did not differ significantly in the presence or absence of the ACEI. Enalaprilat levels also showed no significant difference between the two patient groups treated with AZA or cyclosporine. Hematocrit and hemoglobin increased significantly from 37.5 +/- 6.4 to 39.7 +/- 3.6% (mean +/- SD, P = 0.02) and 12.8 +/- 2.2 to 13.5 +/- 1.2 g/dl, P = 0.04, respectively, 10 to 12 weeks after ACEI treatment had been discontinued. Simultaneously numbers of reticulocytes and erythropoietin concentrations rose significantly after 2, 4 and 10 weeks, with a peak at two weeks (from 14.1 +/- 3.8 to 20.6 +/- 8.0/1000, P < 0.05 and from 14.3 +/- 12.4 to 29.3 +/- 54.5 mU/ml, P < 0.05, respectively). In conclusion, ACEI-related anemia in renal transplant recipients seems to be due to the erythropoietin-lowering effect of this group of drugs. A pharmacokinetic interaction between AZA and enalapril is not likely since plasma enalaprilat levels were independent of the immunosuppressive regimen and AZA metabolite levels were unchanged in the presence and absence of the ACEI. Several mechanisms by which angiotensin converting enzyme blockade may cause a decrease in circulating erythropoietin are discussed.
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PMID:Mechanism of angiotensin converting enzyme inhibitor-related anemia in renal transplant recipients. 887 73

The present study aimed to assess the influence of acetate (AC) and bicarbonate (BI) hemodialysis with a cuprophane membrane on plasma erythropoietin (EPO) levels in 30 patients with chronic renal failure (CRF). Fifteen patients were severely anemic with an Hct below 30%, while 13 were moderately anemic with an Hct equal to or more than 30%. None had received rHuEPO or ACE inhibitors before the study. Blood samples for EPO and pO2 estimation were withdrawn before and after 1, 2 and 5 h of AC dialysis. In 11 of the patients with an Hct < 30% the same protocol was repeated during BI dialysis. In spite of a significant decrease in pO2 during the first hour of AC dialysis, the plasma EPO concentration decreased significantly in both severely and moderately anemic CRF patients from 35.4 +/- 2.6 to 23.6 +/- 3.5 mU/ml after 5 h of hemodialysis (p = 0.0001 by paired t-test) and from 39.5 +/- 8.6 to 27.5 +/- 8.9 mU/ml (p < 0.01) respectively. In contrast to AC dialysis, Bi dialysis failed to change the plasma EPO concentration (from 32.3 +/- 4.1 to 30.3 +/- 4.7 mU/ml after 5 h of hemodialysis). Conclusions AC but not BI hemodialysis shows a significant suppressive effect on plasma EPO levels in anemic CRF patients in spite of a significant decline in pO2. Factors other than pO2 seem to be involved in the regulation of EPO secretion in CRF patients during AC dialysis.
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PMID:Influence of acetate and bicarbonate hemodialysis on the plasma erythropoietin concentration in patients with chronic renal failure. 909 90


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