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Biomedical subjects

E Fleck

Publications and source records attributed to E Fleck.

At least 199 records · Page 11Linked to original sources
PubMed1994

Myocardial cyclic AMP and norepinephrine content in human heart failure.

Impaired production of myocardial cyclic adenosine monophosphate (cAMP) is thought to contribute to contractile dysfunction in end stage heart failure, but myocardial cAMP content has not yet been evaluated in heart failure patients in comparison with controls. We therefore measured the myocardial content of cAMP by radioimmunoassay in endomyocardial biopsies from patients in different stages of heart failure and in controls and correlated it with biochemical and functional parameters. The myocardial content of norepinephrine was determined by HPLC in the same biopsies in order to assess if the myocardium studied was affected by heart failure. Myocardial cAMP (in fmol.microgram-1 non-collagen protein) in 20 patients with heart failure (LVEF: 27 +/- 8%, cAMP: 5.8 +/- 2.0) was unchanged in comparison with eight controls (LVEF: 64 +/- 4.7%, cAMP, 4.9 +/- 2.1). In contrast, myocardial norepinephrine (in pg.microgram-1 non-collagen protein) in the same biopsies was significantly reduced in heart failure (4.0 +/- 3.0) in comparison with the same controls (11.5 +/- 3.0, P < 0.0002). Plasma cAMP in 20 heart failure patients (22.0 +/- 4.2 pmol.l-1) was not different from controls(22.0 +/- 7.8), whereas plasma norepinephrine was increased (heart failure: 460 +/- 257 pg.ml-1, controls 182 +/- 49, P < 0.001). Myocardial cAMP levels are indistinguishable from controls in human heart failure and therefore do not contribute to a further characterization of the cardiac adrenergic system in these patients. This is most likely due to the impossibility of obtaining biopsies with truly unstimulated adenylyl cyclase activity.

Adult↗
PubMed1994

Regulation of the angiotensin receptor subtypes in cell cultures, animal models and human diseases.

With the development of subtype specific angiotensin II (Ang II) receptor antagonists and their introduction into the treatment of heart failure and hypertension, the regulation of the Ang II receptor with its subtypes AT1 and Ang T2 gains clinical importance. In cell cultures, the number of surface AT1 is clearly down-regulated by Ang II exposure. Down-regulation can be due to reversible internalization, to phosphorylation and to reduced synthesis and involves protein kinase C and phospholipase C mediated pathways. In this respect, the AT1 behaves as a typical G-protein coupled receptor. Aldosterone, cAMP, norepinephrine and extracellular glucose concentrations can contribute to AT1 regulation. There are very few data regarding the regulation of the subtype AT2, indicating modulation by a number of growth factors and by Ang II. In whole animal models receptor regulation deviates partially from cell cultures. In the rat, the two subtypes AT1A and AT1B are differentially regulated and the expression of subtypes is organ specific. In most experiments, including our own experiences, the AT1, in the adrenals was up-regulated by Ang II infusion and down-regulated by angiotensin converting enzyme inhibitors (ACEI) or Ang II receptor antagonists. Differing effects were observed in other organs. In humans, a number of studies seeking an association between Ang II levels, Ang II receptor regulation and physiological events have been conducted in platelets. In pregnant women, a negative correlation between plasma Ang II levels and Ang II binding and an association between receptor regulation and pregnancy-induced hypertension has been described.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Clinical results of coronary excimer laser angioplasty: report from the European Coronary Excimer Laser Angioplasty Registry.

From January 1991 to January 1993 the clinical and angiographic data of 470 patients were included in the European Coronary Excimer Laser Angioplasty Registry. Symptoms were CCS class 3 in 23% and CCS class 4 in 14.7%; unstable angina was present in 14.7% and 6.6% of patients had acute myocardial infarction. Of 477 treated lesions, 60% were type B2, and 19% type C. The lesion was located in the LAD in 61%, in the LCX in 16%, in the RCA in 20%, in a protected left main stem in 1.3% and in a saphenous vein graft in 2.5%, respectively. Failure of laser angioplasty occurred in 56 (12%) interventions. By multivariate analysis failure was associated with the intention to treat long segmental lesions (risk ratio (RR) 3.6, confidence interval (CI) 2.9 to 4.4; P = 0.0005), segments with severe prestenotic tortuosity (RR 3.5, CI 2.4 to 4.6; P = 0.02) and total occlusions (RR 2.1; CI 1.4 to 2.8; P = 0.05). Complications included vasospasm (13.4%), dissection (14.7%), flow limiting dissection (4%), reclosure (7.8%), and perforation (1.9%). Myocardial infarction occurred in 2.1%, CABG was requested in 1.9%, and the mortality was 1.5%. Procedural success was achieved in 89%. Individual morphological criteria for a reduced procedural success were the presence of a thrombus (RR 6.4; CI 5.0 to 7.7; P = 0.007) and vessel calcification (RR 2.6; CI 1.9 to 3.2; P = 0.005). Procedural success was slightly lower in type C lesions (86%) than in type B2 (88%) type B1 (95%), and type A lesions (92%), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1994

Isolation and characterization of macrovascular and microvascular endothelial cells from human hearts.

In vivo models to investigate mechanisms of local hemostasis in the macro- and microvascular coronary circulation are not available. Therefore, we established a culture system of human macro- and microvascular endothelial cells with high cellular yield and high endothelial cell purity. Microvascular endothelial cells from human hearts were isolated by enzymatic treatment of cardiac muscle preparations obtained during heart transplantation. The isolated microvessels were used to start cultures that were subsequently separated and purified from contaminating nonendothelial cells by paramagnetic beads linked to the lectin Ulex europaeus agglutinin I. Macrovascular endothelial cells were isolated from epicardial coronary arteries and purified by paramagnetic beads as well. With this method high purity (< 2% nonendothelial cells) was achieved as judged from fluorescence-activated cell sorting. Immunochemistry demonstrated the expression of several typical endothelial markers. The two endothelial cell types displayed functional heterogeneity in respect to bradykinin degradation and plasminogen activator inhibitor-1 activity. Thus the ability to selectively isolate and culture human macro- and microvascular cardiac endothelial cells provides a valuable tool to systematically investigate endothelial function in human hearts.

Bradykinin↗
PubMed1994

Vasomotor responses in cyclosporin A-treated rats after chronic angiotensin blockade.

Chronic angiotensin-converting enzyme (ACE) inhibition prevents endothelial dysfunction in hypertension and hypercholesterolemia. Long-term treatment with cyclosporin A impairs endothelium-dependent relaxations and augments contractions to angiotensin II in the rat aorta. The present study compares vasomotor responses to several vasoconstrictor and dilator stimuli after 6 weeks of oral treatment with either the angiotensin-converting enzyme inhibitor lisinopril (10 mg/kg per day), the angiotensin subtype 1 receptor antagonist D 8731 (10 mg/kg per day), cyclosporin A (15 mg/kg per day), or a combination of cyclosporin A with lisinopril or D 8731 (n = 15 rats per group). Twenty-four hours after the last treatment, aortic rings were mounted in organ chambers for measurement of isometric force. Endothelium-dependent relaxations to acetylcholine and calcium ionophore were impaired by cyclosporin A but not affected by the vasodilators. Cyclosporin A-induced endothelial dysfunction was prevented by cotreatment with lisinopril or D 8731. Relaxations to nitroglycerin, SIN-1, and forskolin were not affected by any treatment. Contractions to phenylephrine and serotonin were reduced by lisinopril but not by D 8731. In contrast, contractions to angiotensin II were augmented by cyclosporin A, lisinopril, and the combination of both but not by D 8731 or D 8731 plus cyclosporin A. The data suggest a role for angiotensin II in cyclosporin A-induced endothelial dysfunction. Chronic ACE inhibition reduces overall smooth muscle contractility. The selective augmentation of angiotensin II effects by ACE inhibition and cyclosporin A suggests upregulation of angiotensin receptors in the aortic smooth muscle by these treatments. Chronic angiotensin subtype 1 receptor blockade does not appear to affect angiotensin receptor function.

Angiotensin II↗
PubMed1994

Tissue kallikrein activity and kinin release in human endothelial cells.

The kininogenase, tissue kallikrein (EC 3.4.21.8), has been identified in different blood vessels. The enzyme was mainly found in vascular smooth muscle cells. It is not known whether it is present and functionally active in vascular endothelial cells. The following study investigates the presence of tissue kallikrein in endothelial cells from human umbilical veins and pulmonary arteries. Tissue kallikrein was demonstrated in three ways: 1) by immunostaining in endothelial cells; 2) by measurement of tissue kallikrein activity using a colorimetric assay; 3) by the measurement of kinin release in intact and homogenised endothelial cells with a radioimmunoassay. Immunostaining demonstrated the presence of tissue kallikrein in endothelial cells from human umbilical veins and endothelial cells from human pulmonary arteries. Tissue kallikrein-like activity, measured by the degradation of D-Val-cyclohexyl-Ala-Arg-4-nitraniline, was 3.57 +/- 0.5 mU/10(6) endothelial cells from human umbilical veins and 7.52 +/- 0.84 mU/10(6) endothelial cells from human pulmonary arteries. Intracellular kinin concentrations were 424 +/- 83 pg/10(6) cells in endothelial cells from human umbilical veins and 576 +/- 146 pg/10(6) cells in endothelial cells from human pulmonary arteries, and they increased in a time-dependent manner after homogenisation. The increase was abolished by aprotinin (1000 kIU), an inhibitor of tissue kallikrein in both cell types. Addition of exogenous kallikrein (5 mU) to homogenised cells led to a five fold increase of kinin concentrations after five minutes, indicating a sufficient resource of cellular kininogen. Removal of extracellularly bound kininogen by washing with dextran sulphate (100 mg/l) resulted in an approximately 75% reduction of the cellular kinin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1994

Dilated cardiomyopathy: computer-assisted analysis of endomyocardial biopsy protein patterns by two-dimensional gel electrophoresis.

In order to identify disease-associated alterations in the myocardial protein patterns in dilated cardiomyopathy, we used 2-dimensional gel electrophoresis to analyse the proteins of endomyocardial biopsies from patients and controls. Proteins (150 micrograms) from biopsies (1-3 mg wet weight) were first separated by isoelectric focusing, then applied to large 2-dimensional gels. A computer-assisted system (PDQUEST) was used for spot detection, quantification and comparison of 2-dimensional protein patterns. From a single endomyocardial biopsy about 1000 different protein species were resolved. The spot pattern was influenced by the concentration of protein during sample preparation, by the amount of protein loaded onto the gels and by the development time of silver staining. Variances of spot position in the first and second dimension and in the long diagonals were less than 5%. Coefficients of variance for the spot quantities in 8 gels were 16 +/- 8%. Contaminating blood proteins could be identified in the biopsy patterns. Computer-assisted comparison between cardiomyopathy (n = 5) and controls (n = 5) over the whole gel revealed that 55 protein spots were increased 100%, 27 protein spots decreased 100%. Four proteins showed significant quantitative differences between the cardiomyopathic hearts and controls. Fourteen proteins were identified by amino acid analysis or microsequencing. An isoelectric point and molecular mass grid was laid over the whole gel based on these identified protein species, resulting in approximate isoelectric point values and molecular masses for all other protein species. Thus, myocardial 2-dimensional protein patterns obtained from endomyocardial biopsies can be used for the characterization of cardiac diseases.

Adult↗
PubMed1994

[A new methodologic approach for determining right ventricular volumes from transesophageal echocardiography].

In order to develop a concept of right ventricular volume estimation accounting for variance in positioning of the transesophageal transducer, non-linear scale transformations of suitable measurements of areas and perimeters were used in a new modeling-approach. This type of modeling supposes self-similarity of ventricular dimensions, a mathematical concept generalizing the notion of proportionality. In a study using right ventricular casts, we were able to demonstrate the geometry of right ventricles complies with these assumptions. The resulting multivariate power law volume estimators were developed by non-linear data fitting by learning-analyses based upon angiographic reference volumes and two areas derived from non-orthogonal sections using a monoplane transducer in a first series of studies, and two orthogonal areas with corresponding perimeters using a biplane device in a second series. Correction factors for systolic and diastolic volumes were applied. By prospective test-analyses angiographic and TEE-derived volumes were compared to evaluate our volume estimator and good agreement was found. Trend was evaluated by correlation amounts to r = 0.95 (n = 22) in series 1 with monoplane transducer, and r = 0.9 (n = 20) in series 2 with biplane transducer. This approach is of use in monitoring right ventricular function in cases with unsuitable transthoracical windows, e.g., in cardiac surgery postoperatively.

Adult↗
PubMed1994

"Medicine on wheels": an opportunity for outreach and housestaff education.

Ambulatory-care teaching programs have been traditionally based in hospital settings. As many patients, in particular the homeless and underinsured, have never reached these settings, we describe a nontraditional outreach health-care program for medical residents. This multidisciplinary program places medical residents on a mobile van to deliver care to a population in New Haven where 18.2% of its families are below the poverty level and have limited or no access to health care at the teaching hospital. On-site urgent care is given along with HIV, pregnancy testing, and blood pressure screening. Health-care follow-up, dental care, alcohol detoxification, and drug counseling are scheduled. A total of 764 adult patients were seen between November 1991 and June 1993 by PGY2 residents on ambulatory rotations. One hundred forty-one patients consented to respond to a questionnaire. Thirty-seven (26%) were homeless with a mean length of homelessness of 15 months. Forty-one percent had been victimized within one year and 33% currently used illicit drugs. The benefits of this unique ambulatory teaching program for medical residents are described.

Adolescent↗
PubMed1994

Hemodynamic and neurohumoral effects of the angiotensin II antagonist losartan in patients with heart failure.

BACKGROUND: Losartan is a specific angiotensin II receptor antagonist with no agonist properties. This agent permits evaluation of the response to selective angiotensin II antagonism in patients with congestive heart failure. OBJECTIVE: A study was designed to assess the acute hemodynamic and neurohumoral response to losartan in a controlled, blinded fashion. DESIGN: Sixty-six patients in New York Heart Association functional class II, III or IV with a radionuclide ejection fraction of < 40% were randomly allocated to treatment with placebo and then sequentially to 5, 10, 25, 75 and 150 mg losartan. Hemodynamic and neurohumoral measurements were obtained at selected times for 24 h following ingestion of a single dose of losartan. RESULTS: Treatment with losartan led to dose-dependent vasodilation. Mean arterial pressure and systemic vascular resistance decreased progressively up to a dose of 25 mg. The higher doses of 75 and 150 mg did not produce additional vasodilation. Similarly, the decrease in pulmonary capillary wedge pressure was not greater with doses exceeding 25 mg. The increase in the cardiac index was modest and similar for all doses. No variation in the heart rate was observed at any dose. The hemodynamic changes were accompanied by marked neurohumoral changes. Large dose-related increases in plasma renin activity and angiotensin II levels were observed, especially following the 150-mg dose. Moderate reductions occurred in serum aldosterone and plasma noradrenaline. The peak effect for these parameters occurred 4-6 h after the dose, with persistent changes still evident 24 h after the dose. CONCLUSIONS: These data demonstrate that selective blockade of the angiotensin II receptor with losartan causes a favorable vasodilatory and neurohumoral response in patients with heart failure. Further studies are needed to determine the most effective dose in these patients. Nevertheless, losartan should be of substantial clinical use in the management of this large population.

Angiotensin Receptor Antagonists↗
PubMed1993

ACE inhibitors are endothelium dependent vasodilators of coronary arteries during submaximal stimulation with bradykinin.

OBJECTIVE: The effect of angiotensin converting enzyme (ACE) inhibitors on vascular tone of isolated coronary arteries was determined in the presence of bradykinin and other vasodilators to elucidate the mechanisms leading to augmented bradykinin effects during ACE inhibition. METHODS: Rings of isolated bovine and human coronary arteries were mounted in organ chambers for measurement of isometric force. The effects of lisinopril, enalaprilat, and captopril were investigated in the presence of submaximal concentrations of bradykinin or other vasodilators. RESULTS: ACE inhibitors alone did not affect vascular tone. Threshold concentrations of bradykinin (10(-10) M), kallidin (10(-9.5) M), and the slowly degraded bradykinin agonists D-Arg(Hyp3)-bradykinin (10(-9.5) M) and [Hyp3-Tyr(Me)8]-bradykinin (10(-10.5) M) caused partial relaxation of bovine rings with endothelium. Subsequent addition of ACE inhibitors markedly potentiated the relaxations to the kinins. Bradykinin concentrations in the organ bath measured by a specific bradykinin radioimmunoassay remained stable during the addition of lisinopril. Variation of the exposure time to bradykinin (10 to 60 min) did not affect the relaxations to the ACE inhibitor. The relaxations to lisinopril were not observed after either removal of the endothelium or incubation with nitro-l-arginine or the bradykinin-2 receptor antagonist Hoe 140. Other vasodilators including acetylcholine, adenosine diphosphate, substance P, or SIN-1 did not prime the rings to respond to ACE inhibitors. Endothelium dependent relaxation to lisinopril and captopril was also observed in human coronary arteries treated with bradykinin (> or = 10(-7) M), but not in those treated with substance P (10(-8) M). CONCLUSIONS: ACE inhibitors selectively potentiate endothelium dependent relaxations to submaximal concentrations of bradykinin in bovine and human coronary arteries by a local mechanism. This effect on endothelial cells might occur in addition to augmented bradykinin concentrations in the blood and reduced angiotensin II generation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Endothelial and vascular smooth muscle function after chronic treatment with cyclosporin A.

We wished to characterize the altered reactivity of vascular smooth muscle and endothelial cells in rat aorta during chronic treatment with cyclosporin. Male adult rats were treated orally for 6 weeks with either cyclosporin A (30 mg/kg/day in 1 ml olive oil, n = 9) or with vehicle alone (n = 10). Rings of isolated thoracic aorta were mounted in organ chambers to measure the change in isometric force in response to smooth muscle-contracting drugs and endothelium-dependent and independent vasodilators. Contractions to potassium chloride (20-80 mM) were markedly reduced in cyclosporin-treated rats. Contractions to phenylephrine (10(-10)-10(-6) M) were reduced at high concentrations (> or = 10(-7) M); those to endothelin-1 (10(-10)-10(-7) M) were not significantly altered. In contrast, contractions to angiotensin II (AII 10(-9)-10(-6) M) were significantly augmented. Endothelium-dependent relaxations to acetylcholine (ACh 10(-8)-10(-5) M) or ADP (10(-7)-10(-5) M) were reduced in cyclosporin-treated rats; endothelium-independent relaxations to SIN-1 (10(-7)-10(-5) M) and atrial natriuretic peptide (ANP 10(-10)-10(-7) M) remained unaffected. Thus, chronic treatment with cyclosporin affects both endothelium-dependent vasodilation and vascular smooth muscle contraction in rat aorta depending on the stimulus applied. The enhanced response to AII and the reduced release of endothelium-derived relaxing factor (EDRF) may contribute to augmented vascular tone and further damage to the arterial wall.

Animals↗
PubMed1993

Effect of angiotensin-converting-enzyme inhibition on bradykinin metabolism by vascular endothelial cells.

The degradation of bradykinin by angiotensin-converting-enzyme (ACE) activity in cultured human endothelial cells was studied by direct measurement of bradykinin and by its effect on the release of endothelium-derived relaxing factors. The half-life of exogenous bradykinin (10,000 pg/ml) was calculated from the decay of the bradykinin concentration as 46 +/- 2 min in cell monolayers, 133 +/- 15 min in conditioned medium, and 24 +/- 2 min in homogenates. Most of the bradykinin-degrading activity in cell monolayers could be inhibited in a concentration-dependent manner by the ACE inhibitors lisinopril, ramiprilat, and captopril. Bradykinin-degrading activity was released into the culture medium containing one-fourth of the bradykinin-degrading activity found in the presence of cell monolayers. In cell homogenates higher unspecific bradykinin-degrading activities were present. The functional consequence of bradykinin degradation was demonstrated by the potentiating effect of ramiprilat on the generation of endothelium-derived relaxing factors nitric oxide and prostacyclin from endothelial cells. The study supports the concept of increased vasodilatory effects of bradykinin during ACE inhibition.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Hemodynamic and neurohormonal effects of the angiotensin II antagonist losartan in patients with congestive heart failure.

BACKGROUND: Losartan is a new specific angiotensin II receptor antagonist with no agonist properties that provides the opportunity to study the consequences of angiotensin II blockade. The objective of the present study was to evaluate the hemodynamic and neurohormonal response to losartan in patients with congestive heart failure. METHODS AND RESULTS: After baseline hemodynamic measurements using balloon-tipped pulmonary artery and radial arterial catheters, patients were randomized to receive a single dose of placebo or 5, 10, 25, 75, or 150 mg losartan in a double-blind, sequential fashion. Hemodynamic and neurohormonal parameters were then measured periodically for 24 hours. Losartan caused vasodilation in a dose-dependent manner. By the area-under-the-curve method, the reduction in the mean arterial pressure and systemic vascular resistance grew larger up to a dose of 25 mg, but the higher 75- and 150-mg doses did not produce additional vasodilation. In response to losartan, there were compensatory increases in both angiotensin II concentrations and in plasma renin activity, which were greatest at the highest doses. Aldosterone concentrations were significantly lowered with losartan. CONCLUSIONS: Blockade of the angiotensin II receptor with the antagonist losartan causes vasodilator and neurohormonal effects in patients with congestive heart failure. The lack of additional vasodilator response with doses of more than 25 mg suggests that neurohormonal activation might limit the efficacy of high dose of losartan.

Angiotensin II↗
PubMed1993

Bronchial hyperreactivity in patients with moderate pulmonary circulation overload.

The clinical course of congestive heart failure (CHF) and mitral valve stenosis (MVS) is accompanied by episodes of dyspnea, wheezing, and cough, symptoms also observed in patients with bronchial hyperreactivity. However, it is still controversial whether bronchial hyperreactivity is demonstrable in patients with chronic overload of the pulmonary circulation. In order to examine the effects of CHF on the respiratory function, we performed pulmonary function tests, titrated bronchial acetylcholine provocations, and left and right heart catheterization in 21 patients with impaired left ventricular function (mean ejection fraction, 37 percent, NYHA class 3), 5 patients with MVS, and 17 control patients with coronary artery disease (mean ejection fraction, 63 percent). Bronchial hyperresponsiveness was defined as an obstructive response to increased doses of inhaled acetylcholine. A 20 percent fall in forced expiratory volume in the first second (FEV1), a 100 percent increase in total airway resistance (Rtot), and a 60 percent reduction of pulmonary conductance (SGtot) were considered positive. Patients with impaired left ventricular function showed significantly higher airway resistance, and lower airway conductance at the maximal tolerated acetylcholine dose compared with control patients. Patients with MVS had a significant lower airway conductance. The induced bronchial obstruction was completely reversible upon inhalation of a beta 2-mimetic. We conclude that chronic overload of the pulmonary circulation is accompanied by bronchial hyperreactivity that may augment the symptoms of dyspnea in patients with CHF and MVS.

Acetylcholine↗
PubMed1993

Degradation of bradykinin by neutral endopeptidase (EC 3.4.24.11) in cultured human endothelial cells.

The presence of neutral endopeptidase 24.11 was demonstrated in human umbilical vein endothelial cells by immunostaining. Enzymatic activity of neutral endopeptidase was determined as 0.167 +/- 0.02 mU/mg protein in the membrane fraction of human umbilical vein endothelial cells, using the fluorogenic peptide substrate, dansyl-D-Ala-Gly-Phe(pNO2)-Gly. No activity was found in the cytosolic fraction of endothelial cells. The role of this peptidase in the degradation of the endogenous vasodilator bradykinin was investigated by incubating human umbilical vein endothelial cell monolayers with bradykinin (10(-8) mol/l). The inhibitor of neutral endopeptidase, phosphoramidon (10(-8) mol/l), decreased the degradation of bradykinin in the supernatant of endothelial cells; the half-life of bradykinin was then increased from 29 +/- 1 to 46 +/- 2 minutes. The angiotensin-converting enzyme inhibitor, lisinopril (10(-8) mol/l), increased the half-life of bradykinin to 244 +/- 20 minutes; the combination of both inhibitors increased the half-life of bradykinin to 381 +/- 51 minutes. Inhibitors of aminopeptidase (amastatin) and carboxypeptidase (2-mercaptomethyl-3-guanidinoethyl-thiopropionic acid) caused no significant effect. The effect of phosphoramidon was small in comparison with that of lisinopril, but was pronounced in combination with lisinopril. Neutral endopeptidase activity is localized in the membranes of human endothelial cells and seems to be involved in the degradation of bradykinin by the vascular endothelium, particularly during angiotensin converting enzyme inhibition.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

[Diagnosis of the dynamic lesion].

Rupture of atheromatous plaques, thrombosis and spastic contractions cause dynamic lesions in coronary arteries. This review focuses on the diagnostic approach to vasospastic lesions. Our current knowledge considers vasospastic angina as a--most likely--localized disease of the vascular smooth muscle, which occurs in nonatherosclerotic as well as in atherosclerotic segments. Currently the diagnosis can only be proven by functional tests under angiographical control. Since the pathophysiological mechanisms leading to vasospasm remain unclear, only empirically developed pharmacological tests are available. The use of ergonovine alkaloids is well established, the feasibility of acetylcholine is under investigation. The reproducibility regarding the course of the disease and the localization of the lesion has not yet been determined. The necessity to state the diagnosis is given by the improved prognosis of the disease under effective therapy with calcium channel blockers and nitrates.

Acetylcholine↗