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Biomedical subjects

E Fleck

Publications and source records attributed to E Fleck.

At least 163 records · Page 9Linked to original sources
PubMed1996

Reduced atrial angiotensin receptor type 1 mRNA content in end-stage human heart failure: assessment by a novel quantitative PCR-ELISA technique.

The number of atrial angiotensin II binding sites is reduced in end-stage human heart failure. The goals of our study were the development of a quantitative polymerase chain reaction for angiotensin II receptor type 1 mRNA to determine the angiotensin receptor type 1 (AT1) mRNA content in the atria of patients with end-stage heart failure. We established a quantitative PCR based on coamplification of AT1 wild-type and an internal standard in the same PCR, followed by liquid-phase hybridization of PCR products in microtiter plates and quantitation by ELISA. Glyceraldehyde phosphate dehydrogenase mRNA in the same samples was used to relate the AT1 mRNA content to a stably expressed reference gene. Atrial samples from 11 patients with end-stage heart failure obtained at cardiac transplantation were compared with atrial samples from 11 patients with normal cardiac function undergoing routine cardiac surgery. A PCR/ELISA system with a variance of about 6% after reverse transcription and a linear measuring range was established. In the samples from 11 patients with end-stage heart failure a 58% decrease in AT1 mRNA content was found in comparison with 11 controls (heart failure: 185,680 +/- 196,912 AT1 mRNA copies/microgram RNA, controls: 440,555 +/- 268,456, P < 0.02). When AT1 mRNA content was related to glyceraldehyde phosphate dehydrogenase mRNA, a 65% decrease was detected (AT1/glyceraldehyde phosphate dehydrogenase: heart failure: 4.84 +/- 5.18; controls: 13.74 +/- 7.77; P < 0.005). Standardization of PCR resulting in a low coefficient of variance, high reproducibility, and large sample capacity is possible using optimal internal standardization and the liquid-phase hybridization/ELISA system for detection. The optimized PCR procedure indicated downregulation of atrial AT1 in end-stage human heart failure, suggesting a reduced capacity of the atria to respond to angiotensin II stimulation in end-stage heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Subtype 2 and atypical angiotensin receptors in the human heart.

Angiotensin receptors have been described in the human heart and are suspected to play a central role in remodeling after myocardial infarction and in cardiac hypertrophy. Two subtypes, AT1 and AT2, have so far been described in humans, with AT2 being the dominant subtype in human atria. We have now determined subtype numbers and distribution by binding in ventricular myocardium from patients with end-stage heart failure. We found about 50-80% of subtype AT2 in the right and left ventricles from patients with end-stage heart failure due to coronary artery disease and cardiomyopathy, indicating that AT2 is the dominant angiotensin receptor subtype in the whole human heart. To determine the cellular localization of angiotensin receptors in human myocardium in addition to the known localization on myocytes, smooth muscle cells and endothelial cells, we investigated cardiac fibroblasts. They express an angiotensin receptor with yet incompletely understood binding characteristics which is coupled to proliferation and DNA synthesis. As AT2 is the dominant angiotensin receptor subtype in human heart, we cloned the complete mRNA sequence by a rapid amplification of cDNA ends (RACE) procedure and thereafter the promoter sequence from a human genomic library. Once the sequence of the mRNA and thus exon 1 was obtained by the RACE-PCR, a probe was constructed for the most 5' region of exon 1 and used for screening of a human genomic DNA bank. After cutting of the positive clones with EcoR1 and Not1, a 4000 bp fragment hybridized with the probe and was further sequenced. A functional AT2 promoter, with > 90% homology with the mouse promoter and 35% homology with the human AT1 promoter containing numerous cis-acting sequences for basal (TFIID) and inducible (AP-1, PEA-3, CBF) transcription factors in the first 1000 bp was identified.

DNA↗
PubMed1996

Decreased expression of ventricular angiotensin receptor type 1 mRNA after human heart transplantation.

Myocardial angiotensin receptors of type 1 (AT1) are downregulated at the protein and mRNA levels in human heart failure. No data are available for the transplanted human heart, which frequently exhibits functional alterations. The aim of the present study was the quantitation of ventricular AT1 mRNA content in endomyocardial biopsies from patients after heart transplantation. For the determination of AT1 mRNA we used a novel quantitative reverse transcription polymerase chain reaction with low variance (6%) based on an internal AT1 cRNA standard, liquid-phase hybridization of polymerase chain reaction products in microtiter plates, and quantitation by enzyme-linked immunosorbent assay. Right ventricular biopsies from 16 patients after heart transplantation (left ventricular ejection fraction 67 +/- 7%) were compared with 12 patients with normal cardiac function (left ventricular ejection fraction 62 +/- 5%). A 46% lower AT1 mRNA content was found in biopsies from the 16 patients after heart transplantation than in the 12 controls (heart transplantation, 200 +/- 25 AT1 mRNA copies/ng RNA; controls, 368 +/- 50; P < 0.01). When AT1 mRNA content was related to the stably expressed GAPDH mRNA, a 49% decrease was detected (AT1/GAPDH: patients, 2.4 +/- 0.25; controls, 4.7 +/- 0.6; P < 0.006). No association between the extent of AT1 downregulation and clinical or hemodynamic variables was detected. In the human heart ventricular AT1 is downregulated after orthotopic heart transplantation. The decrease in AT1 mRNA is not associated with altered systolic function. This may partially reflect a loss of autonomic nerves and thus altered nervous control of the heart.

Adolescent↗
PubMed1996

Isolation and characterisation of human cardiac fibroblasts from explanted adult hearts.

Fibrosis makes an important contribution to the pathophysiological events leading to the development of heart failure in ischemic and hypertensive heart disease. Since cardiac fibroblasts are mainly responsible for the synthesis and deposition of the extracellular matrix, we have established a method for isolating and cultivating human cardiac fibroblasts from explanted human hearts. The cell yield was 2.14+/-0.25x10(6 )cells in five independent isolations and the cell purity was 95-97%, contaminating cells being vascular smooth muscle cells and pericytes. Cultured cells were studied with respect to growth properties, morphology and deposition of components of the extracellular matrix. Isolated cells displayed a differentiated phenotype, including the second passage in culture; they synthesised collagen I, III, IV, fibronectin, vitronectin, tenascin and chondroitin sulphate and expressed an atypical angiotensin receptor. This atypical angiotensin receptor internalised angiotensins II and III but not angiotensin IV in a time-dependent manner. Stimulation of the cells with angiotensins II and III but not with angiotensin IV resulted in a dose-dependent stimulation of DNA synthesis. Co-incubation with the subtype-specific receptor antagonists Losartan and PD 123317 did not prevent the stimulation of DNA synthesis. The further characterisation of this receptor should provide insights into the pathobiochemical events leading to heart failure in hypertension and ischemic heart disease.

Adult↗
PubMed1996

Accuracy and precision of angiographic volumetry methods for left and right ventricle.

We imaged and quantified 60 ventricle casts (30 LV, 30 RV) to evaluate the accuracy and reliability of angiographic ventricle volumetry. We analyzed the seven biplane methods most frequently used in clinical routine: Arcilla, Arvidsson, Dodge, Ferlinz, Simpson (LV + RV) and Wynne. The ventricle contours were defined by (1) manual drawing on the computer screen, (2) manual drawing using a graphical tablet and (3) automatic contour detection. A high inter-class variation in volume accuracy between the different methods was observed (S.D. = 12.7 ml). The volume methods for the LV (mean differences MDLV: [-2.2, +8.5] ml, average MDLV = 1.8 ml) are more accurate than for the RV (MDRV: [-11.4, +33.1] ml, average MDRV = 12.1 ml). The intrinsic error is about the same for all approaches and is very high: average S.D. = 20 ml, RMS = 185 ml. Manual contour definition results in a volume over-estimation (average MDman = +32.8 ml, r = 0.731) compared with automatic contour detection (average MDauto = +6.2 ml, r = 0.810). LV hypertrophy results in a volume under-estimation of the LV (MDLV = -7 ml) and an over-estimation of the RV (MDRV = +6 ml). RV hypertrophy leads to the opposite effect. It was shown that ventricle volumetry and the calculation of derived parameters (ejection fraction) is extremely case dependent and can only be an estimate of the actual value.

Angiography↗
PubMed1996

Cyclic flow variations after angioplasty: a rare phenomenon predictive of immediate complications. DEBATE Investigator's Group.

Experimental studies and studies in human beings have indicated that cyclic flow variation (CFV) is a reliable marker of the formation of platelet aggregates and thus may be predictive of immediate complications after coronary angioplasty. In this study, the incidence and clinical relevance of CFV in a large patient population after elective percutaneous transluminal coronary angioplasty (PTCA) was assessed. One hundred two patients with one-vessel disease and no previous Q-wave myocardial infarction underwent angiographically successful PTCA of a single lesion of a major coronary artery. A Doppler guide wire inserted distal to the stenosis was used to monitor flow velocity continuously after PTCA for 15 minutes. In 94 (92%) of 102 patients, a stable and reliable Doppler signal could be recorded for 15 minutes after the procedure. CFV, defined as gradual decline in flow over several minutes followed by a sudden restoration to higher values, was observed in 4 patients. In 3 of these 4 patients, the occurrence of CFV was predictive of immediate complications (2 intracoronary thrombosis and 1 acute closure), whereas none of the patients without CFV (n = 90) showed acute closure during hospital stay. In conclusion, CFVs in patients after angiographically successful elective PTCA are rare (4.3%) but highly sensitive for the prediction of abrupt occlusion.

Aged↗
PubMed1996

[3-D visualization of thoracic tumors from MR images].

AIM: In cooperation with the thoracic surgery department 3-D visualizations of tumors were generated to support the surgeons in preoperative planning. As opposed to 3-D reconstructions of CT data, those representations based on MRI images remain an exception. In this paper different methods of three dimensional visualization of lung tumors are presented and compared to each other. DESIGN: These methods are 1. contour based surface models, 2. threshold based surface models and 3. rendered scenes of segmented volume data with transparent, color-coded display. RESULTS: Combinations of all three methods in one single image are possible as well with the software we developed. Furthermore, cut planes through the original data can be integrated into the 3-D scene. The segmentation of anatomical objects is performed either manually or automatically with various procedures. CONCLUSIONS: Adequate possibilities of manipulation and archiving allow a fast handling and processing even of large data sets. The calculated volumes of the anatomical objects can be used for quantitative studies. Arbitrary views of the three dimensional reconstructions can be generated within a few seconds. Even animation can easily be calculated and displayed with 30 frames/second.

Adult↗
PubMed1996

[Computer graphics methods for 3-dimensional imaging of intrapulmonary space-occupying lesions of CT and MRI images].

AIM: To improve the pre-operative planning of interventional procedures in thorax surgery different methods of computer-graphical visualization of intrapulmonary lesions and adjacent anatomical structures based on CT and MR data were realized and compared to each other. DESIGN: In 21 patients with intrapulmonary lesions the image data was segmented by interactive and automatic algorithms and different reconstruction techniques were applied (maximum intensity projection; color-encoded and transparent surfaces; volume rendering). Based on these three-dimensional reconstructions, different views from arbitrary perspectives (including simulated endoscopic images) were generated and animated film sequences of the 3D scene were displayed with 30 frames/second. RESULTS: For all patients under review, a high-quality presentation of the relevant structures was obtained by use of the applied computer-graphical techniques. Even combinations of different visualization methods in one image can be generated with the software we developed. CONCLUSIONS: The various methods for image segmentation allow a fast and comfortable processing even of large data sets. The calculated values of tumor surface and volume can be used for quantitative studies and therapy control. The planning of surgical and interventional procedures can be supported by the simultaneous visualization of the intrathoracic lesion and the surrounding structures.

Aged↗
PubMed1995

Selective downregulation of rat cardiac beta 1-adrenoceptors by cyclosporine A: prevention by diltiazem or angiotensin-converting enzyme inhibitors.

OBJECTIVES: This study attempted to determine whether long-term treatment with cyclosporine A in rats affects cardiac beta 1-adrenoceptors and whether this can be prevented by angiotensin-converting enzyme inhibitors or calcium-entry blocking agents. BACKGROUND: In the transplanted human heart the density of beta 1-adrenoceptors decreases with time after transplantation, whereas that of beta 2-adrenoceptors does not. Because heart transplant recipients are treated with cyclosporine A, we studied whether administration of cyclosporine A in rats might cause this beta 1-adrenoceptor downregulation. METHODS: We performed two studies. First, we treated groups of 10 male normotensive Wistar rats orally with 30 mg/kg body weight per day of cyclosporine A, 10 mg/kg per day of enalapril and 60 mg/kg per day of diltiazem, alone or in combination, for 6 weeks each. Second, we treated groups of 15 male normotensive Wistar rats orally with 15 mg/kg per day of cyclosporine A and 10 mg/kg per day of lisinopril, alone or in combination, for 6 weeks each. At the end of each treatment regimen, cardiac beta-adrenoceptor density and subtype distribution were assessed by (-)-[125I]iodocyanopindolol binding. RESULTS: Both doses of cyclosporine A caused a significant decrease in cardiac beta 1-adrenoceptor density without affecting beta 2-adrenoceptor density. Although diltiazem and the angiotensin-converting enzyme inhibitors alone did not affect cardiac beta-adrenoceptors, they prevented the cyclosporine A-induced downregulation of beta 1-adrenoceptors. CONCLUSIONS: In normotensive Wistar rats, cyclosporine A causes a significant decrease in cardiac beta 1-adrenoceptors without affecting beta 2-adrenoceptors. This can be prevented by diltiazem or angiotensin-converting enzyme inhibitors. In heart transplant recipients, who undergo long-term treatment with cyclosporine A, there is a very similar beta 1-adrenoceptor down-regulation with time after transplantation. Thus, administration of cyclosporine A may cause these beta-adrenoceptor subtype alterations.

Animals↗
PubMed1995

Regulation, chamber localization, and subtype distribution of angiotensin II receptors in human hearts.

BACKGROUND: To assess the chamber localization, subtype distribution, and regulation of human myocardial angiotensin II receptors in heart failure, we determined the binding of angiotensin II, Sar1Ile8-angiotensin II, and the subtype-specific antagonists Dup 753 (AT1-specific) and PD 123319 (AT2-specific) in atria from patients with normal (left ventricular ejection fraction > 55%) or moderately impaired (left ventricular ejection fraction 30% to 55%) cardiac function and in atria and ventricles from explanted end-stage failing hearts. Sarcolemmal and combined fractions, the latter including internalized receptors, were studied. In addition, AT1 mRNA content was analyzed by polymerase chain reaction after reverse transcription. METHODS AND RESULTS: The number of angiotensin II binding sites (Bmax) in sarcolemmal fractions was significantly reduced in explanted end-stage failing hearts in comparison with control subjects and moderate heart failure (Bmax 3.9 +/- 0.8 versus 11.2 +/- 1.7 and 9.6 +/- 0.8 fmol/mg protein, respectively). A comparable 65% reduction in receptor numbers was found in combined fractions from end-stage failing hearts, indicating that the loss of binding sites was not due to their internalization. The dissociation constants were comparable in sarcolemmal and combined fractions and in nonfailing and failing hearts, ranging from 0.5 +/- 0.2 to 1.2 +/- 0.5 nmol/L. In nonfailing hearts, 69 +/- 4% of binding sites were blocked by the subtype-2-specific inhibitor PD 123319 and were therefore classified as AT2; 33 +/- 5% were blocked by the subtype-1-specific inhibitor DUP 753 and thus classified as subtype 1. In explanted hearts, comparable ratios of 66 +/- 5% AT2 sites and 34 +/- 5% AT1 sites were found. AT1 cDNA amplification signals by polymerase chain reaction were reduced to about one third of the level in control subjects in end-stage failing hearts. CONCLUSIONS: Angiotensin II receptors in human myocardium are present in relatively low numbers, and AT2 is the predominant subtype. A significant loss of angiotensin II receptors occurs in end stage but not in moderate heart failure. The loss of receptors affects both subtypes to a comparable degree. The data suggest that the decrease in receptor density is due to a decrease in steady-state mRNA abundance.

Binding Sites↗
PubMed1995

Chamber-specific expression of human myocardial proteins detected by two-dimensional gel electrophoresis.

High resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), followed by computer-assisted image analysis (PDQUEST) was used to screen atrial and ventricular protein patterns for quantitative and qualitative differences in protein expression. Myocardial proteins from left ventricular (LV) and right atrial (RA) samples from end-stage, failing explanted hearts and from a healthy donor heart (control) were separated by 2-D large gel electrophoresis. Ten RA versus ten LV gels from explanted dilated cardiomyopathic (DCM) hearts were analyzed for quantitative differences in their spot patterns. Of the 197 spots matched to every gel, 40 spots differed significantly in intensity between RA and LV for DCM patients. A larger number of atrial and ventricular gels (20 RA, 20 LV) from DCM patients and from a healthy donor heart (4 RA, 4 LV gels) were analyzed for qualitative differences in protein expression. Three protein spots (SSP 1120: M(r)/pI:20.5 kDa/4.6; SSP 1119: M(r)/pI:20.6 kDa/4.5; SSP 0117:M(r)/pI:20.7/ < 4.5) that are present in all RA gels for DCM patients are absent in all LV gels. Two protein spots (SSP 0112: M(r)/pI:17.2 kDa,/ < 4.4; SSP 0114:M(r)/pI:17.6 kDa/ < 4.4) occur only in all LV gels but not in the RA gels. These five qualitatively differing spots are identical in DCM patients and in the healthy donor heart. Some of the differing spots were internally sequenced and identified as myosin light chain isoforms (myosin light chain 2, atrial; myosin light chain 2, ventricular; myosin light chain 1, atrial) with the Protein Identification Resource (PIR) accession numbers A44451, S03708, A30881, respectively. Additionally, phosphoglycerate mutase (PIR: JQ0750) and ATP synthase alpha chain (PIR: S17193) were identified. Thus, quantitative and qualitative differences between atrial and ventricular protein patterns were identified by 2-D PAGE. A characteristic distribution of myosin light chains between atrial and ventricular human myocardium was found using our approach.

Amino Acid Sequence↗
PubMed1995

Effect of theophylline on beta-adrenergic receptor density and cAMP content in bovine aortic smooth muscle cells.

Activation of vascular beta-adrenergic receptors prevents an increase in vascular permeability caused by free radicals or inflammatory peptides. Methylxanthines seem to have similar protective effects on vascular endothelium. In the present study we investigated the effect of theophylline on the beta-adrenergic receptor expression and cAMP concentrations in cultured endothelial and smooth muscle cells from bovine aorta. Comparable values for beta-receptor density and binding affinity were detected in both cell types. Isoproterenol induced significant downregulation of beta-receptors in endothelial (BAEC: -60.5%) and smooth muscle cells (BASMC: -52.5%; P < 0.01). Incubation of endothelial cells with theophylline (4 micrograms/ml and and 40 micrograms/ml) for 24 hours did not affect beta-receptor expression, whereas in smooth muscle cells the beta-receptor density was reduced for -31.5% and -28.7%, respectively. In endothelial cells a transient effect on cAMP concentrations was observed after stimulation with isoproterenol (1 microM), but no effect was found in theophylline treated endothelial cells. Stimulation of intact smooth muscle cells with isoproterenol and theophylline (4 micrograms/ml and 40 micrograms/ml) resulted in a significant increase of cAMP concentrations after 60 and 240 minutes. The present data suggest a novel, celltype specific effect of theophylline on the beta-adrenergic receptor expression in vascular smooth muscle cells in vitro.

Adrenergic beta-Agonists↗
PubMed1995

Angiotensin-converting enzyme inhibitors and beta-blockers in long-term treatment of dilated cardiomyopathy.

This double-blind, randomized, long-term study investigated the effects of the angiotensin-converting enzyme inhibitor enalapril and the beta-blocker metoprolol on clinical, hemodynamic, angiographic, and neurohormonal parameters in patients with dilated cardiomyopathy and moderate cardiac functional impairment (left ventricular ejection fraction [LVEF] 35% +/- 6%). After 12 months of treatment, a 12% reduction in 24-hour heart rate was observed in both groups (p < 0.05), whereas heart rate during exercise was reduced only in the metoprolol group. Echocardiographic fractional shortening increased (enalapril: 17% +/- 6% to 21% +/- 7%; metoprolol: 21% +/- 9% to 29% +/- 7%; both p < 0.05), as did the angiographic LVEF (enalapril: 35% +/- 7% to 43% +/- 12%, p = 0.1; metoprolol: 34% +/- 7% to 44% +/- 9%, p < 0.05), whereas ventricular volume decreased. Initially, both groups were comparable in terms of all parameters investigated. After 12 months fractional shortening was greater, and the heart rate at 50 W was lower in the beta-blocker group. At the doses used, the effect of the beta-blocker on dilated cardiomyopathy with moderate functional impairment was at least as great as that of the angiotensin-converting enzyme inhibitor.

Adrenergic beta-Antagonists↗
PubMed1995

Activation of adenylate cyclase and phosphodiesterase inhibition enhance neutral endopeptidase activity in human endothelial cells.

Endothelial neutral endopeptidase (EC 3.4.24.11, NEP) contributes to the inactivation of vasoactive and inflammatory peptides such as f-Met-Leu-Phe, substance P, atrial natriuretic peptide, and bradykinin. The aim of the present study was to investigate the cellular regulation of NEP expression in human endothelial cells, focusing on the role of cyclic nucleotides and cellular phosphodiesterases (PDE). Activation of adenylate cyclase by forskolin or prostaglandin E1 (PGE1) induced an increase of NEP activity and NEP protein after 24 h of incubation. This effect was mimicked by two activators of protein kinase A, dibutyryl-cAMP and 8-bromo-cAMP. The nonspecific PDE inhibitor, 3-isobutyl-1-methylxanthine (200 microM), increased NEP activity up to 192%. The activator of guanylate cyclase, sodium nitroprusside (SNP), did not affect NEP activity but completely inhibited the 3-isobutyl-1-methylxanthine-mediated increase of NEP activity. The PDE-III inhibitors motapizone (100 microM) and enoximone (100 microM) enhanced NEP activity up to 188% and 213%, the PDE-IV inhibitor rolipram (3 microM) up to 162%, and the combined PDE-III/IV inhibitor zardaverine (1 microM) up to 176% of control values. The present data provide evidence for a cAMP-mediated increase of NEP activity in human endothelial cells.

Adenylyl Cyclases↗
PubMed1995

[The correction for motion and visualization of subtraction angiographic data from the spiral CT].

Conventional image subtraction of CT sequences is hampered by extended motion artifacts. In this paper a motion correction procedure for the subtraction of images from two time-separate CT investigations is introduced. Native images are obtained in the first CT sequence, and a contrast medium examination is imaged in the second. The aim of image subtraction is sole presentation of the contrast medium. In contrast to conventional digital subtraction angiography (DSA), CT angiography rules out the possibility of direct image subtraction due to occurrence of extended motion artifacts in the time-shifted images. Such shortcomings can now be corrected by means of a new registration method developed for determination of local displacement vectors between the two images. This motion pattern is used to compute a new synthetic mask of maximum congruence with the contrast medium image. The resulting three-dimensional data record is presented by means of a special-purpose hardware enabling fast rotations and cut planes. New diagnostic possibilities can be achieved such as the creation of views that are not obtainable with conventional modalities and the assessment of calcified vessels.

Angiography, Digital Subtraction↗
PubMed1995

Endothelium-mediated vasodilation during ACE inhibition.

ACE inhibitors are superior to other vasodilators in the treatment of congestive heart failure and may be advantageous in patients with myocardial infarction and hypertension. The mechanisms mediating these beneficial effects are not clear. The present article discusses the mechanisms leading to augmented release of endothelium-derived nitric oxide during ACE inhibition. Acute potentiation of bradykinin (Bk)-induced vasodilation was studied in rings of bovine and human coronary arteries mounted in organ chambers for recording of isometric force. The ACE inhibitors captopril, enalaprilat, fosinoprilat, lisinopril, or ramiprilat alone did not affect vascular tone in isolated coronary tone in isolated coronary artery preparations with intact endothelium. However, in the presence of exogenous Bk, kallidin, or one of the slowly degradable Bk2-receptor agonists D-Arg(Hyp3)-Bk or [Hyp3-Tyr(Me)8]-Bk they elicited potent concentration-dependent relaxations. Relaxations in response to lisinopril were not observed in the presence of other vasodilators. They were prevented by mechanical removal of the endothelium, inhibition of nitric oxide synthase or Bk2-receptor blockade. The data indicate that ACE inhibitors potentiate the effects of Bk on endothelial cells by a local mechanism, probably independent of the degradation of bradykinin. The chronic effects of ACE inhibitors on endothelial function were compared with those of selective angiotensin(AT)1-receptor blockade in cyclosporin A (CsA) treated rats. Chronic AT blockade alone does not affect endothelium-dependent relaxation and increases contractions to ATII in the rot aorta. Combination of CsA with either an ACE-Inhibitor or an AT2 receptor antagonist prevented the endothelial dysfunction in the rat arta observed after CsA alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗