enalapril and Ischemia

The purpose of this study was to evaluate the structural and functional effects of systemic oxygen therapy and enalapril in patients with diabetic macular ischemia (DMI). This randomized clinical trial consisted of 105 eyes with DMI divided into three groups. Group I received systemic oxygen by face mask at a flow rate of 10 L/min; Group II received 5 mg enalapril daily; and Group III received placebo tablets for 3 months. Best-corrected visual acuity (BCVA), central macular thickness (CMT) measured by optical coherence tomography (OCT), extent of foveal avascular zone (FAZ) on fluorescein angiograms, and electroretinograms (ERG) were obtained at baseline and after 3 and 6 months. Overall, 102 patients completed the study. Baseline characteristics were not significantly different among groups. Significant improvement in BCVA and decrease in CMT and FAZ occurred at months 3 and 6 in oxygen group compared to deterioration in enalapril and control groups (All P values <0.001). ERG parameters were significantly better in oxygen group compared to enalapril group at months 3 and 6 and better than those in control group at month 3. Normobaric oxygen therapy for 3 months in DMI decreased CMT and FAZ and improved BCVA and ERG parameters. Enalapril did not show any favorable effect.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Diabetic Retinopathy; Enalapril; Female; Humans; Ischemia; Macula Lutea; Macular Edema; Male; Middle Aged; Oxygen; Retinal Diseases; Tomography, Optical Coherence; Visual Acuity

Angiotensin-converting enzyme inhibitors have different effects on the cardiovascular system. The aim of this study was to investigate the effect of enalapril on skeletal muscle angiogenesis in diabetic and diabetic hind limb ischemic rats.. We studied 24 male diabetic rats (induced by streptozotocin, 55 mg/kg, ip) divided into four groups. Groups 1 and 2 were diabetic sham (surgical procedure without femoral artery ligation). Groups 3 and 4 were diabetic animals subjected to induced hind limb ischemia. Groups 2 and 4 received enalapril (15 mg/kg/day, i.p) and groups 1 and 3 received an equal volume of saline. After 21 days, capillary density, capillary to fiber (cap/fib) ratio and serum concentrations of nitric oxide (NO), Vascular Endothelial Growth Factor (VEGF) and soluble VEGF Receptor-1 (sVEGF-R1) were evaluated.. Enalapril significantly increased serum NO and VEGF concentrations and reduced serum sVEGF-R1 concentrations in diabetic sham and hind limb ischemic rats (p<0.05). Administration of enalapril significantly increased capillary density and cap/fib ratio in diabetic sham and hind limb ischemic animals compared with nontreated groups (p<0.05).. Enalapril restores skeletal muscle angiogenesis in diabetic hind limb ischemia and can be considered for the prevention and treatment of peripheral artery disease in diabetic subjects.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Enalapril; Hindlimb; Ischemia; Male; Muscle, Skeletal; Neovascularization, Physiologic; Nitric Oxide; Rats; Rats, Wistar; Receptors, Vascular Endothelial Growth Factor; Vascular Endothelial Growth Factor A

Enalapril, an angiotensin-converting enzyme (ACE) inhibitor, reduces cardiovascular events in patients with acute myocardial infarction. However, whether the beneficial effect of enalapril is mediated in part through endothelial progenitor cells (EPCs) has yet to be elucidated. This study investigated the role of the CD26/dipeptidylpeptidase IV (DPP IV) system in enalapril-modulated EPC mobilization. C57 BL/6 mice were divided into control and enalapril-treated groups. Peripheral EPCs were enumerated before and after ischemic stress. CD26/DPP IV activity and stroma-derived factor-1alpha (SDF-1alpha) levels were measured in the blood and the bone marrow. In response to ischemic stress, the enalapril group displayed a significant increase in circulating EPCs (with a 3.6-fold increase of sca-1+KDR+ cells and a 2.2-fold increase of c-kit+CD31+ cells versus controls at 12 h). Enalapril also caused a sixfold increase in the contribution of bone marrow-derived EPCs to the ischemia-induced neovascularization. In the bone marrow, enalapril did not alter CD26+ cell numbers; however, it did amplify DPP IV activity. In the blood, through the anti-inflammatory effect, enalapril significantly decreased CD26+ cell numbers, leading to a decrease in total DPP IV activity. These phenomena were associated with a lower SDF-1alpha concentration in the bone marrow but higher in the blood in the enalapril group, compared to the controls. All these findings were not demonstrated without ischemic stress. The effect of enalapril on EPC mobilization could be substantially blocked by Diprotin-A, a DDP IV antagonist. This study demonstrates that one of the pleiotropic effects of enalapril on the cardiovascular system involves the modulation of circulating EPC numbers via the CD26/DPP IV system, which may serve as a potential target for mobilizing EPCs for therapeutic purposes.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood; Bone Marrow Cells; Cell Differentiation; Cells, Cultured; Chemokine CXCL12; Chemokines, CXC; Cytokines; Dipeptidyl Peptidase 4; Enalapril; Epithelial Cells; Humans; Ischemia; Lower Extremity; Male; Mice; Mice, Inbred C57BL; Oligopeptides; Stem Cells

The purpose of our research was to study the pattern of post-ischemic cerebral hemodynamic changes and observe the impact of enalapril on the course of these changes in cats.. The experiments were carried out on anesthetized cats using the autohemoperfusion method in cerebral and peripheral vessels with a stable volume of blood. Transitional peripheral (lower limb) and brain ischemia was simulated by stopping the autohemoperfusion pump for 15 minutes, tying various anastomoses in the neck region, and reducing arterial blood pressure (ABP) to 40-30 mm Hg, followed by reinfusion of the shed blood.. Intravenous administration of enalapril solution in a dosage of 0.25 mg kg-1 in the early phase of reperfusion (10 minutes into the postischaemic period) prevented the development of long-term "no-reflow"of cerebral blood flow, as observed in the controls. There was a 40.8+/-3.2% reduction of cerebrovascular tone, 39.3+/-3.1% in peripheral vessels, and 44.7+/-1.5% lower arterial blood pressure at the end of 120 minutes.. Enalapril caused a reduction of cerebrovascular tone, completely eliminating the "no-reflow" syndrome after brain ischemia and somewhat potentiated the hyperperfusion phase. At the same time, the drug did not aggravate the general hypotension observed after ischemia in the controls.

Topics: Animals; Arteriovenous Anastomosis; Brain; Brain Ischemia; Cats; Cerebrovascular Circulation; Enalapril; Extremities; Ischemia

The inappropriate use of antihypertensive medications may cause hypotensive responses associated with organ failure. We describe a patient who developed nonocclusive splanchnic ischemia leading to death following the administration of enalapril to treat postoperative hypertension. The mechanisms and consequences of refractory hypotension induced by angiotensin-converting enzyme inhibitors are discussed.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arthritis, Rheumatoid; Colon; Enalapril; Fatal Outcome; Female; Humans; Hypertension; Ischemia; Multiple Organ Failure; Necrosis; Postoperative Complications; Splanchnic Circulation

A reduction in glomerular filtration rate (GFR) is a primary characteristic of ischemic acute renal failure. The present study was undertaken to examine the roles of angiotensin II, tubuloglomerular-feedback (TGF) mechanism, and tubular obstruction for the GFR reduction in the post-ischemic kidney. Renal ischemia was induced by occlusion of the bilateral renal arteries for 60 min, and renal function was examined at 2 and 24 h after the onset of reflow. After the end of 2-h reflow, the GFR was not significantly changed, but the urine flow increased significantly. On the other hand, at the end of 24-h reflow, the GFR and urine flow decreased markedly along with increased filtration fraction. The renal blood flow significantly decreased at 24 h, but not 2 h, after reflow, which was accompanied by increased total renal vascular resistance. Furosemide infusion (1 mg/min/kg) after 24 h of reflow prevented the reduction in GFR and filtration fraction without no changes in renal blood flow and total renal vascular resistance. Pretreatment of enalapril and losartan did not prevent the reduction in GFR, indicating that angiotensin II was not involved. In morphological examinations, tubular obstruction was seen in the proximal and distal tubules of kidneys both at 2 and 24 h after the onset of reflow. In two rabbits subjected to 48 h of reflow, the tubular obstruction was not observed, despite GFR remained depressed. These results suggest that the late reduction in GFR in postischemic kidneys is not mediated by angiotensin II, but is mediated, at least in part, by the TGF mechanism. The tubular obstruction may be not prerequisite for the GFR reduction in rabbits.

Topics: Acute Kidney Injury; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Biomarkers; Creatinine; Enalapril; Female; Glomerular Filtration Rate; Ischemia; Kidney; Kidney Tubules; Losartan; Male; Rabbits; Renal Circulation; Urodynamics

Rats recovering from acute renal ischemia exhibit tubule loss and interstitial fibrosis followed by development of proteinuria and glomerular sclerosis. The current study assessed the contribution of angiotensin II (AngII) to these processes. The contribution of AngII to early tubule loss and interstitial fibrosis was assessed in rats studied for 35 d after right nephrectomy and transient occlusion of the left renal artery. One group of rats received no treatment, while a second group received losartan beginning at 2 d following ischemia. Studies at 35 d showed that losartan did not improve GFR (2.04 +/- 0.30 ml/min treated, 2.16 +/- 0.21 ml/min untreated), reduce the fraction of glomeruli that were no longer connected to normal tubule segments (42 +/- 9% treated, 42 +/- 13% untreated), or limit expansion of the interstitial volume fraction (25 +/- 3% treated, 25 +/- 4% untreated). The contribution of AngII to progressive glomerular injury following initial recovery from ischemia was assessed in similarly prepared rats studied for 140 d. One group of rats received no treatment, while a second group received enalapril beginning at 35 d following ischemia. Enalapril markedly reduced proteinuria (78 +/- 17 mg/d treated, 229 +/- 52 mg/d untreated) and the prevalence of segmental glomerular sclerosis (14 +/- 9% treated, 45 +/- 10% untreated). Untreated rats developed sclerotic lesions in glomeruli not connected to normal tubules, as well as in glomeruli connected to normal tubules. Enalapril prevented injury in both classes of glomeruli. These results indicate that AngII does not contribute to interstitial fibrosis during recovery from ischemic injury. Reduction of AngII activity, can, however, prevent secondary glomerular injury in kidneys initially damaged by ischemia.

Topics: Acute Disease; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Disease Progression; Enalapril; Ischemia; Kidney; Losartan; Male; Rats; Rats, Sprague-Dawley; Renal Circulation; Time Factors

Angiotensin-converting enzyme (ACE) inhibitors have proven to be effective in the reduction of ischemia/reperfusion damage after myocardial ischemia. Whether this favorable effect can be related to other models of ischemia and reperfusion has not yet been investigated. Therefore, we studied in a model of syngeneic liver transplantation in the rat the effect of recipient enalapril treatment on postischemic liver injury. Untreated animals served as the control group. Treatment with enalapril was started 5 minutes before reperfusion by intravenous infusion of enalapril at a dosage of 5 mg/kg/h. By means of in vivo microscopy, the sinusoidal perfusion rate and leukocyte adherence in sinusoids and postsinusoidal venules were analyzed during 45 to 60 minutes of reperfusion. Liver function was monitored by measuring bile output over a period of 60 minutes. Analysis of coagulation factors (prothrombin time, factor V, fibrinogen) and liver enzymes (alanine transaminase [ALT], aspartate transaminase [AST]) served for the evaluation of organ dysfunction and damage secondary to ischemia/reperfusion injury. The sinusoidal perfusion rate was significantly improved by enalapril treatment (94.7% [1.0] vs. 75.3% [3.8]; mean [SEM]; P = .005). In addition, leukocyte-sticking in both liver sinusoids and postsinusoidal venules was remarkably reduced in enalapril-treated animals as compared with controls (stickers/lobule: 21.0 [3.3] vs. 59.2 [2.1]; P = .0004; stickers/mm2 venular surface: 20.5 [4.7] vs. 110.3 [18.1]; P = .0004). Moreover, bile output was increased (1.13 [0.35] vs. 0.43 [0.18] g bile/60 min x 100 g liver; P = .06). Values for PT (22.5% [2.1] vs. 9.7% [1.8]; P = .005), factor V 99.4% [9.5] vs. 49.5% [8.5]; P = .007), and fibrinogen (64.1% [7.7] vs. 12.8% [3.2]; P = .001) were significantly improved, paralleled by a remarkable reduction in serum ALT (1,428 U/L [190] vs. 2,315 [248]; P = .02). Our data show for the first time that ACE inhibition in the liver recipient by enalapril attenuates hepatic ischemia/reperfusion damage after experimental liver transplantation. Our results may offer a novel approach to reduce ischemia/reperfusion injury in clinical liver transplantation.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Enalapril; Ischemia; Liver; Liver Transplantation; Male; Microcirculation; Rats; Rats, Inbred Lew; Reperfusion Injury

Previous studies have shown that the renin-angiotensin axis plays a pivotal role in vasoconstriction of the gastric, intestinal, and hepatic circulations during cardiogenic shock. The aim of this study was to evaluate the fundamental hemodynamic mechanism of pancreatic ischemia during cardiogenic shock induced by pericardial tamponade.. Cardiogenic shock was induced by pericardial tamponade. Cardiac output (and total peripheral vascular resistance) was determined by thermodilution. Pancreatic blood flow (and vascular resistance) was determined with radiolabeled microspheres.. Graded increases in pericardial pressure produced corresponding decreases in cardiac output to 42% +/- 1% and arterial pressure to 67% +/- 3% of baseline and increases in total peripheral vascular resistance to 146% +/- 5% of baseline. Pancreatic blood flow decreased disproportionately to 30% +/- 3% of baseline, because of a disproportionate increase in pancreatic vascular resistance to 220% +/- 19% of baseline. Previously confirmed blockade of the renin-angiotensin axis ablated this response, whereas confirmed blockade of the alpha-adrenergic system or vasopressin system had no significant effect. Without shock, central intravenous infusions of angiotensin II closely mimicked this selective vasoconstriction.. Angiotensin-mediated selective pancreatic vasoconstriction results in significant pancreatic ischemia during cardiogenic shock.

Topics: Adrenergic alpha-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Animals, Newborn; Cardiac Tamponade; Enalapril; Hemodynamics; Ischemia; Pancreas; Phenoxybenzamine; Regional Blood Flow; Shock, Cardiogenic; Swine

Multiunit and single-unit recordings of afferent renal nerve activity (ARNA) were obtained in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats between 35 and 150 days of age. Intrapelvic backflow of urine at 20 mmHg excited ARNA at all ages in SHR (152 +/- 18% above control) and WKY rats (262 +/- 24%). In SHR, complete renal ischemia was more excitatory in rats older than 120 days (1,233 +/- 103%, n = 8) than in younger SHR (317 +/- 28%, n = 42). Single-unit recordings showed that this was related to the appearance of R1 chemoreceptors in older SHR and coincided with a decline in the proportion of R2 chemoreceptors in the renal nerves. Other chemoreceptive responses were identified in single units that did not show complete R1 or R2 characteristics, some of which showed responses consistent with a transformation process from R2 to R1 receptor type. R1 chemoreceptors were not present in WKY rats studied up to 150 days of age and, unlike SHR, the proportion of R2 chemoreceptors did not decline with age. Accordingly, complete renal ischemia in WKY rats caused a comparable excitation in multiunit ARNA at all ages (285 +/- 33%, n = 43). Oral enalapril from weaning to 100 days of age prevented hypertension in SHR but did not impair the responsiveness of ARNA to any stimulus. In WKY rats, enalapril treatment for the same period resulted in exaggerated ARNA response to renal ischemia (1,250 +/- 377% above control).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Afferent Pathways; Aging; Animals; Chemoreceptor Cells; Electrophysiology; Enalapril; Hypertension; Ischemia; Kidney; Nervous System; Neurons; Potassium Chloride; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Renal Circulation; Urine

The influence of the renin-angiotensin system on renal hemodynamics, tubular pressure and tubulo-glomerular feedback was investigated with the angiotensin converting enzyme inhibitor MK 421 (enalapril), in uninephrectomized rats with and without ischemia-induced acute renal failure. In animals with normal renal function proximal tubular pressure and tubulo-glomerular feedback response were lowered by enalapril long-term treatment, whereas glomerular filtration rate and renal blood flow were not influenced by the drug. After 45 and 70 minutes ischemia there was no difference between treated and untreated animals in the severely impaired glomerular filtration rate. Renal blood flow remained unaffected by the treatment. The histological damage due to ischemia (tubular casts, tubular necrosis and medullary capillary congestion) was not influenced by enalapril. As tubulo-glomerular feedback had been significantly inhibited during renin-angiotensin inhibition, its importance in mediating acute renal failure remains doubtful; other factors such as tubular obstruction and medullary congestion may be crucial.

Topics: Acute Kidney Injury; Angiotensin-Converting Enzyme Inhibitors; Animals; Enalapril; Feedback; Female; Hemodynamics; Ischemia; Kidney Glomerulus; Kidney Tubules; Rats; Rats, Inbred Strains; Renal Artery Obstruction; Renal Circulation; Thrombosis