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Biomedical subjects

K Becker

Publications and source records attributed to K Becker.

At least 91 records · Page 5Linked to original sources
PubMed2001

Human thioredoxin reductase is efficiently inhibited by (2,2':6',2' '-terpyridine)platinum(II) complexes. Possible implications for a novel antitumor strategy.

Malignant neoplasms of the brain represent the second leading cause of cancer-related mortality in children under the age of 15. The prognosis of patients with glioblastoma multiforme, the most malignant type of gliomas, remains poor offering a median survival time of only 1 year. (2,2':6',2"-Terpyridine)platinum(II) complexes are known to possess DNA-intercalating activity and have been shown to be potential chemotherapeutic agents. In the present study we identified the selenoenzyme thioredoxin reductase (TrxR) as a major target of (2,2':6',2"-terpyridine)platinum(II) complexes. New complexes were synthesized in order to optimize this inhibition. The NADPH-reduced enzyme is inhibited almost stoichiometrically by the complexes involving a reversible competitive and an irreversible tight-binding component. For the most potent inhibitor, N,S-bis(2,2':6',2"-terpyridine)platinum(II)-thioacetimine trinitrate, the K(i) for the competitive component of the inhibition is 4 nM and the IC(50) for the tight-binding component is 2 nM after an incubation time of 5 min. The closely related but non-selenium-containing enzyme glutathione reductase is much less inhibited (by a factor of >1000). The platinum complexes were found to strongly inhibit the proliferation of three different glioblastoma cell lines as well as of two different head-and-neck squamous carcinoma cell lines. In a glioblastoma cell culture, less than 10 microM of a platinum(II) compound caused an initial drop of hTrxR activity which was followed by an increase of activity in the surviving cells. A 10 microM inhibitor added every 24 h led to 4% residual hTrxR activity but 100% glutathione reductase activity in the cells surviving for 67 h. The potential of (2,2':6',2"-terpyridine)platinum(II) complexes acting simultaneously at two different intracellular targets-hTrxR and DNA-as antitumor agents is discussed.

2,2'-Dipyridyl↗
PubMed2001

Plasmodium falciparum possesses a classical glutaredoxin and a second, glutaredoxin-like protein with a PICOT homology domain.

The genes coding for two different proteins with homologies to glutaredoxins have been identified in the genome of the malarial parasite Plasmodium falciparum. Both genes were amplified from a gametocytic cDNA and overexpressed in Escherichia coli. The smaller protein (named PfGrx-1) with 12.4 kDa in size exhibits the typical glutaredoxin active site motif "CPYC," shows glutathione-dependent glutaredoxin activity in the beta-hydroxyethyl disulfide (HEDS) assay, and reduces Trypanosoma brucei ribonucleotide reductase. Glutathione:HEDS transhydrogenase activity (approximately 60 milliunits/mg of protein) was clearly detectable in trophozoite extracts from eight different P. falciparum strains and did not differ between chloroquine-resistant and -sensitive parasites. Five different antimalarial drugs at 100 microm did not significantly influence isolated PfGrx-1 activity. In contrast, the second protein (deduced mass 19.9 kDa) with homology to glutaredoxins (31% identity to Schizosaccharomyces pombe in a 140-amino acid overlap) was not active in the HEDS assay; however, its general dithiol reducing activity was demonstrated in the insulin assay in the presence of dithiothreitol. Interestingly, the sequence contains a PICOT (for protein kinase C-interacting cousin of thioredoxin) homology domain, which might suggest regulatory functions of the protein. We named this protein PfGLP-1, for P. falciparum 1-Cys-glutaredoxin-like protein-1. In contrast to glutaredoxins, PfGLP-1 could not be reduced by glutathione. This is the first report on glutaredoxin-like proteins in the family of Plasmodia.

Amino Acid Sequence↗
PubMed2001

Analysis of cellular factors influencing the replication of human immunodeficiency virus type I in human macrophages derived from blood of different healthy donors.

We analyzed parameters influencing HIV-1 infectibility of cells of the monocyte/macrophage lineage (MO/MAC) isolated from different healthy donors. The proportion of in vitro-infected cells and replication kinetics in different donor MAC ranged from 0.03 to 99% p24 antigen-positive MAC and from undetectable RT activity up to 5 x 10(6) cpm/ml/90 min, respectively. As a quantitative measurement for HIV-1 susceptibility of donor MO/MAC, we determined TCID(50) values of defined virus stocks which varied up to 3000-fold depending on the donor MAC used for titration. As host factors which may influence the viral infection we determined the expression of virus receptors CD4, CCR5, CXCR4, and CCR3 as well as the secretion of the natural ligands of CCR5, which altogether showed no correlation with HIV-1 infectibility of the cells. Moreover, other MO-derived secretory factors which might affect viral infection of these cells could be excluded. Furthermore, expression of maturation-related antigens CD14, CD16, HLA-DR, and MAX.1/CPM was determined. Analysis of the reverse transcription process revealed that restricted HIV-1 infection was reflected by highly reduced or even undetectable full-length HIV-1 DNA formation, although early and intermediate transcripts appeared, suggesting that viral replication is blocked after entry at the level of early reverse transcription.

Blood Donors↗
PubMed2001

Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging.

PURPOSE: Preoperative chemotherapy in patients with gastroesophageal cancer is hampered by the lack of reliable predictors of tumor response. This study evaluates whether positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) may predict response early in the course of therapy. PATIENTS AND METHODS: Forty consecutive patients with locally advanced adenocarcinomas of the esophagogastric junction were studied by FDG-PET at baseline and 14 days after initiation of cisplatin-based polychemotherapy. Clinical response (reduction of tumor length and wall thickness by > 50%) was evaluated after 3 months of therapy using endoscopy and standard imaging techniques. Patients with potentially resectable tumors underwent surgery, and tumor regression was assessed histopathologically. RESULTS: The reduction of tumor FDG uptake (mean +/- 1 SD) after 14 days of therapy was significantly different between responding (-54% +/- 17%) and nonresponding tumors (-15% +/- 21%). Optimal differentiation was achieved by a cutoff value of 35% reduction of initial FDG uptake. Applying this cutoff value as a criterion for a metabolic response predicted clinical response with a sensitivity and specificity of 93% (14 of 15 patients) and 95% (21 of 22), respectively. Histopathologically complete or subtotal tumor regression was achieved in 53% (eight of 15) of the patients with a metabolic response but only in 5% (one of 22) of the patients without a metabolic response. Patients without a metabolic response were also characterized by significantly shorter time to progression/recurrence (P =.01) and shorter overall survival (P =.04). CONCLUSION: PET imaging may differentiate responding and nonresponding tumors early in the course of therapy. By avoiding ineffective and potentially harmful treatment, this may markedly facilitate the use of preoperative therapy, especially in patients with potentially resectable tumors.

Adenocarcinoma↗
PubMed2001

Opposing effects of molecular volume and charge at the hyperekplexia site alpha 1(P250) govern glycine receptor activation and desensitization.

Allelic variants of the glycine receptor alpha1 subunit gene GLRA1 underlie the human neurological disorder hyperekplexia. Among these, the subunit variant alpha1(P250T) is characterized by an amino acid substitution within the cytoplasmic TM1-2 loop. To identify structural elements at position alpha1(250) that govern receptor function, homomeric mutant receptor channels were subjected to electrophysiological analysis after recombinant expression in HEK293 cells. Wild-type alpha1(P250) channels were nondesensitizing with an EC(50) for glycine of 8 microm, whereas bulky hydrophobic side chains of the channel variants alpha1(P250V/I/L/F) showed rapid desensitization (tau(desens), 50-250 ms) and EC(50) values of 400-1800 microm. Small side chains (P250G/A/S) gave rise to wild-type-like channels. Effects of volume were counteracted by charge: alpha1(P250E/R) were nondesensitizing; EC(50) was approximately 70 microm. The mutants alpha1(P250C/Y) displayed intermediate channel properties (EC(50), 42/70 microm; tau(desens), 3300/2800 ms, respectively). The isotropic forces volume and hydropathy were sufficient to account for the observed effects of residue alpha1(250) on receptor function. Indeed, channel behavior was best predicted by a combined hydropathy/volume index describing the hydrophobic surface of individual amino acids. These observations characterize the short intracellular TM1-2 loop as a regulatory domain for channel activation and a crucial mediator of glycine receptor desensitization.

Alleles↗
PubMed2001

Intracellular persistence of Staphylococcus aureus small-colony variants within keratinocytes: a cause for antibiotic treatment failure in a patient with darier's disease.

Intracellular persistence assays were performed with small-colony variants (SCVs) derived from a patient with Darier's disease from whom different phenotypes and genotypes of Staphylococcus aureus were isolated over a 28-month period; the assays revealed that >100-fold more SCV cells persisted intracellularly relative to the normal phenotype. The presence of intracellular S. aureus SCVs may protect against host defenses and antibiotic therapy and thus may have contributed to this patient's very prolonged skin infection.

DNA, Bacterial↗
PubMed2001

Histamine poisoning associated with eating tuna burgers.

CONTEXT: Histamine poisoning occurs when persons ingest fish in which bacteria have converted histidine to histamine, a process that usually can be controlled by storage at low temperatures. From 1994 to 1997, North Carolina averaged 2 cases annually; however, from July 1998 to February 1999, a total of 22 cases of histamine fish poisoning were reported. OBJECTIVES: To examine the increase in histamine case reports, identify risk factors for poisoning, and develop recommendations for prevention. DESIGN AND SETTING: Case series evaluated in North Carolina from July 1998 to February 1999. SUBJECTS: Reported case-patients with 2 of the following symptoms within 2 hours of eating tuna: rash, facial flushing, vomiting, diarrhea, dyspnea, a tight feeling in the throat, headache, or a metallic or peppery taste in the mouth. RESULTS: Twenty cases occurred during 5 outbreaks, and there were 2 single occurrences. Of the 22 persons affected, 19 (86%) sought emergency medical care. All case-patients ate tuna: 18 ate tuna burgers, 2 ate salad containing tuna, and 2 ate filets. Tuna samples (available from 3 outbreaks) had histamine levels above the Food and Drug Administration regulatory level of 50 ppm (levels were between 213 and 3245 ppm). In 19 cases, the tuna used to prepare burgers or salads was frozen and thawed more than once before serving. Violations of recommended temperature controls were identified in 2 of the 5 restaurants, accounting for 14 (64%) cases. CONCLUSIONS: Tuna burgers, a relatively new menu item in restaurants, were associated with an increase in histamine poisoning cases in North Carolina. Tuna ground for burgers can be susceptible to both temperature fluctuations and bacterial contamination.

Animals↗
PubMed2001

Neoadjuvant therapy for patients with locally advanced gastric carcinoma with etoposide, doxorubicin, and cisplatinum. Closing results after 5 years of follow-up.

BACKGROUND: The intent to curatively treat patients with gastric carcinoma is based on complete surgical resection of the primary tumor and its lymphatic drainage. Postoperative adjuvant chemotherapy has failed to show a significant prognostic advantage for these patients. Preoperative chemotherapy, based on promising results in the treatment of patients with disease in primarily unresectable stages, is still being evaluated for those with locally advanced gastric carcinoma. Most published studies still lack adequate staging methods, and long term results of this treatment modality are not known at present. METHODS: In a Phase II study, a series of 42 patients with locally advanced gastric carcinoma (International Union Against Cancer Stages IIIA, IIIB, and IV) initially were staged with endoscopy, with endoscopic ultrasound to establish the clinical tumor classification, with computed tomography scans to rule out tumor infiltration of adjacent organs and to detect distant metastases, and with surgical laparoscopy to exclude occult peritoneal carcinomatosis. Three or four planned cycles of neoadjuvant chemotherapy with etoposide, doxorubicin, and cisplatinum were given prior to total gastrectomy. RESULTS: After a complete follow-up of at least 5 years, there was a median survival of 19.1 months for all patients. Only patients who underwent a complete surgical tumor resection appeared to have a survival benefit, with a median survival of 28.4 months. A superior survival rate was seen in patients who had a major clinical response to chemotherapy, with a median survival of 45 months. CONCLUSIONS: Phase III studies comparing results from patients who undergo neoadjuvant chemotherapy followed by surgery with results from patients who undergo surgery alone should stress the value of adequate pretherapeutic staging and must be accompanied by studies of potential methods for predicting tumor response.

Adolescent↗
PubMed2001

Substitution of the thioredoxin system for glutathione reductase in Drosophila melanogaster.

The disulfide reducing enzymes glutathione reductase and thioredoxin reductase are highly conserved among bacteria, fungi, worms, and mammals. These proteins maintain intracellular redox homeostasis to protect the organism from oxidative damage. Here we demonstrate the absence of glutathione reductase in Drosophila melanogaster, identify a new type of thioredoxin reductase, and provide evidence that a thioredoxin system supports GSSG reduction. Our data suggest that antioxidant defense in Drosophila, and probably in related insects, differs fundamentally from that in other organisms.

Amino Acid Motifs↗
PubMed2001

[Preoperative risk assessment and perioperative management of HIV-infected patients].

PROBLEM: Due to their impaired immune function, unusual multimorbidity, and extensive concomitant medication HIV-infected patients impose special and specific demands on those who deal with their perioperative care. PREOPERATIVE ASSESSMENT: Beside standardized diagnostic and therapeutic preparations the preoperative knowledge, quantification, and treatment of HIV-associated opportunistic disorders and chronic organ damage are of particular importance. This requires an extended problem-orientated work-up. Furthermore, antiretroviral medication may interact with perioperatively administered pharmaceutics and lead to hardly foreseeable synergistic and antagonistic adverse effects. In contrast, "drug holidays" favor the development of HIV drug resistance. OPERATIVE MANAGEMENT: Anesthetic and surgical procedures basically depend on the underlying indication and consequently follow common principles. Laparoscopic techniques do not have any specific advantage in HIV-infected subjects. PERIOPERATIVE MORBIDITY: During their postoperative course, HIV-infected patients have to be more often admitted to intensive care unit and kept on artificial respiration unplannedly. Perioperative morbidity of HIV-infected patients increases with the stage of their disease. It is, however, not significantly elevated compared to that of HIV-negative subjects in similar preoperative health condition.

Anti-HIV Agents↗
PubMed2001

Nasal carriage as a source of Staphylococcus aureus bacteremia. Study Group.

BACKGROUND: The consequences of infection with Staphylococcus aureus can be severe, so strategies for prevention are important. We examined S. aureus isolates from blood and from nasal specimens to determine whether the organisms in the bloodstream originated from the patient's own flora. METHODS: In a multicenter study, swabs for culture were obtained from the anterior nares of 219 patients with S. aureus bacteremia. A total of 723 isolates were collected and genotyped. In a second study, 1640 S. aureus isolates from nasal swabs were collected over a period of five years and then compared with isolates from the blood of patients who subsequently had S. aureus bacteremia. RESULTS: In the multicenter study of S. aureus bacteremia, the blood isolates were identical to those from the anterior nares in 180 of 219 patients (82.2 percent). In the second study, 14 of 1278 patients who had nasal colonization with S. aureus subsequently had S. aureus bacteremia. In 12 of these 14 patients (86 percent), the isolates obtained from the nares were clonally identical to the isolates obtained from blood 1 day to 14 months later. CONCLUSIONS: A substantial proportion of cases of S. aureus bacteremia appear to be of endogenous origin since they originate from colonies in the nasal mucosa. These results provide support for strategies to prevent systemic S. aureus infections by eliminating nasal carriage of S. aureus.

Adolescent↗
PubMed2001

Species/variety differences in biochemical composition and nutritional value of Indian tribal legumes of the genus Canavalia.

Seeds of the Indian tribal pulses Canavalia gladiata (red and brown varieties), C. ensiformis and C. virosa were analysed for their physical characters, proximate composition, minerals, amino acid composition, dietary fibre constituents, starch fractions, fatty acid profiles and various antinutritional and/or toxic factors. Among the different species/varieties of Canavalia, the brown variety of C. gladiata was found to have the highest amount of protein (35.0%). The essential amino acid profile of total seed proteins compared favourably with the FAO/WHO reference pattern established for pre-school children, except for a deficiency of sulphur containing amino acids in both varieties of C. gladiata and C. ensiformis, whereas high concentrations of cystine and methionine were detected in C. virosa. However, tryptophan in the red variety and lysine in the brown variety of C. gladiata seemed to be the second most limiting amino acids. Generally, these Canavalia seeds appear to be a good source of potassium, phosphorus and calcium. They contain low levels of sodium. Even though the samples contained a high proportion of total starch (31.8-36.9%), the percentage of digestible starch appeared to be much higher in C. ensiformis (70.6%) and C. virosa (71.8%) than in C. gladiata. The seed lipids of all the Canavalia samples investigated had a large proportion of unsaturated fatty acids (71-78%) with oleic acid as the major one (38.6-47.4%). All samples were rich in dietary fibre (17.5-23.6%), most of which was insoluble dietary fibre. The level of the toxic amino acid, canavanine, was found to be relatively low (27-42%) in C. gladiata and C. ensiformis compared to previous literature reports for the same species. The other antinutrients such as phenolics, tannins, condensed tannins, saponins, protease inhibitors, alpha-amylase inhibitor and haemagglutinating activity were also analysed and reported here. C. ensiformis seeds exhibited a relatively high level (69.0%) of in vitro protein digestibility compared to the red (67.2%) and brown (65.4%) varieties of C. gladiata and C. virosa (62.5%).

Amino Acids↗
PubMed2001

Survey of staphylococcal enterotoxin genes, exfoliative toxin genes, and toxic shock syndrome toxin 1 gene in non-Staphylococcus aureus species.

The aim of this study was to analyze the presence of staphylococcal exotoxin genes in staphylococci other than Staphylococcus aureus. Whereas for Staphylococcus aureus a large spectrum of different exotoxins responsible for toxin-mediated diseases has been described, only few and conflicting data are available regarding toxin production in all other staphylococcal species. A collection of clinical non-Staphylococcus aureus staphylococcal isolates were systematically screened for the presence of genes for toxic shock syndrome toxin 1, exfoliative toxins, and classical enterotoxins by using multiplex polymerase chain reaction enzyme immunoassays. In a total of 461 isolates of 18 different (sub)species derived from clinical specimens, no toxin gene sequences were amplified. The results indicate that the occurrence of toxin genes involved in staphylococcal toxin-mediated diseases is at least very rare in human-derived isolates of non-Staphylococcus aureus species.

Bacterial Toxins↗
PubMed2001

[Spectrum and results of operative interventions in HIV infection patients].

Owing to their number, multimorbidity, and prolonged survival following improved antiretroviral therapy, HIV-infected subjects represent an important subgroup of the patients requiring surgical treatment. The spectrum of operative interventions performed in these people comprises both characteristic diagnostic, palliative, and therapeutic measures and all the same surgical indications as in an age-matched non-HIV-infected patient population. Published data concerning the results of operative interventions in these patients are rather scarce. The surgical success rate is 68-90% for elective therapeutic measures. In 21-94% of HIV-infected patients intraoperative findings of a HIV-associated opportunistic disease are reported. Depending on patient selection and the kind of operation performed, the perioperative morbidity of these subjects was 9-87% (median 33.5%), while postoperative mortality ranged from 0 to 71% (median 8%). Particular determining factors of perioperative morbidity and mortality are the degree of individual immunosuppression and the urgency of surgical intervention. In summary, operation-associated morbidity and mortality of HIV-infected patients appear not to be significantly increased compared to non-HIV-infected patients in similar preoperative health condition. The present analysis reflects a marked improvement of operative results in HIV-infected patients during the past 20 years.

AIDS-Related Opportunistic Infections↗
PubMed2001

[Static-dynamic MR urography. Comparison with excretory urography and scintigraphy in experimentally-induced urinary tract obstruction].

PURPOSE: To assess the diagnostic value of combined static-dynamic MR urography (MRU) for the functional-morphological evaluation of experimentally induced urinary tract obstruction. METHODS: Static-dynamic MRU--combination study with a respiratory-triggered 3D-IR-TSE sequence and a dynamic 2D-FFE sequence after Gd-DTPA and furosemide--was obtained in comparison with 99mTc-MAG3 diuretic renal scintigraphy (DRS), excretory urography (EU) and ultrasound (US) in 29 healthy piglets and in 20 piglets with surgically induced ureteric stenosis (total of 50 postoperative examination blocks). RESULTS: MRU allowed complete depiction of the urinary tract in all controls, in operated piglets the stenosis was always correctly identified. Quality of MRU was superior to EU in 36 of 43 comparative studies. Calculation of single kidney function from parenchymal renograms, and assessment of urinary excretion from whole-kidney renograms resulted in a highly significant agreement of MRU with DRS. CONCLUSION: Static-dynamic MR urography allows excellent depiction of experimentally induced urinary tract obstruction, and reliable assessment of individual renal function and urinary excretion. Two advantages of the method stand out, it does not require radiation and it permits a functional-morphological correlation.

Animals↗
PubMed2001

Inositolphosphate formation in thoracic and abdominal rat aorta following Gq/11-coupled receptor stimulation.

Although thoracic and abdominal rat aorta are often used as a classical pharmacological preparation for the assessment of vascular drug effects, little is known on regional differences among these two parts of the aorta with regard to their reaction to Gq/11-coupled receptor activation. Thus, we determined, in rings from thoracic and abdominal aorta from 12-week-old male Wistar rats, the effects of noradrenaline (NA; 10(-8)-10(-4) M), endothelin-1 (ET-1; 10(-10)-10(-6) M) and the thromboxane A2 mimetic U 46619 (10(-8)-10(-5) M) on inositolphoshate (IP) formation (assessed as accumulation of total [3H]IPs in [3H]myoinositol prelabelled rings). NA, ET-1 and U 46619 concentration-dependently increased IP formation; maximum increases were, however, significantly more pronounced in thoracic than in abdominal aorta. Similarly, NA, ET-1 and U 46619 evoked significantly larger maximum contractions in thoracic than in abdominal aorta. NA-induced [3H]IP formation could be inhibited with BMY 7378 (10(-9)-10(-4) M) and with 5-methyl-urapidil (5-MU; 10(-9)-10(-5) M) both exhibiting biphasic concentration-inhibition curves. The pKi-values for BMY 7378 at the high affinity site were in thoracic aorta 8.93+/-0.28 (n=5), and in abdominal aorta 8.76+/-0.35 (n=4) and at the low affinity site 6.45+/-0.2 (thoracic aorta) and 6.55+/-0.27 (abdominal aorta). pKi-Values for 5-MU in thoracic aorta at the high affinity site were 8.25+/-0.34 (n=4), and at the low affinity site 6.61+/-0.39 . In abdominal aorta reliable pKi-values could not be calculated for 5-MU due to a low signal-to-noise ratio. On the other hand, in both preparations the ETA-receptor antagonist BQ-123 (10(-9)-10(-5) M) and the TP-receptor antagonist SQ 29548 (10(-9)-10(-5) M) inhibited ET-1- and U 46619-induced IP formation, respectively, with monophasic concentration-inhibition curves: pKi-values for BQ-123 were: 8.16+/-0.24 (thoracic aorta) and 8.10+/-0.35 (abdominal aorta) and for SQ 29548: 8.2+/-0.3 (thoracic aorta) and 8.5+/-0.3 (abdominal aorta). The amount of immunodetectable Gq/11-protein was similar in both tissues. We conclude that responses to NA, ET-1 and U 46619 (IP formation and contractile force) are larger in thoracic than in abdominal aorta. ET-1 effects on IP formation are mediated by ETA-receptors and U 46619 effects by TP-receptors. NA effects are mediated by alpha1D- and alpha1A-adrenoceptors; alpha1B-adrenoceptors seem to play a minor role.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

ET-receptor function in relation to blood pressure in spontaneously hypertensive and aortic-banded rats.

Endothelin-1 (ET-1), a potent endogenous vasoconstrictor, has been proposed to play a pathophysiologic role in hypertension. The aim of this study was to find out whether changes in ET-receptor function are cause or consequence of blood pressure elevation in hypertension. For this purpose, we assessed ET-receptor function [as ET-1-induced [3H]inositol phosphate (IP) accumulation] in slices of left ventricle and renal cortex and in rings of thoracic and abdominal aorta from spontaneously hypertensive rats (SHR) at the age of 8 weeks (i.e. developing hypertension), 12 and 24 weeks (established hypertension) vs. normotensive age-matched Wistar-Kyoto (WKY) rats, and from supra-renal aortic-banded (AOB) rats at the age of 8, 12 and 24 weeks (i.e. 4, 8 and 20 weeks after AOB) vs. sham-operated (SOP) age-matched WKY rats. In the SHR with established hypertension ET-1-induced IP formation was altered in all tissues investigated: it was significantly increased vs. WKY rats in left ventricle, and significantly decreased in renal and aortic tissues. Similarly, in AOB rats at all ages ET-1-induced IP formation was changed in those tissues that were under pressure load [heart (increase) and thoracic aorta (decrease)] vs. SOP rats, whereas in those tissues not under pressure load (kidney and abdominal aorta) ET-1-induced IP formation was not different between AOB and SOP rats. Moreover, in 8-week-old SHR (where hypertension is not yet established) ET-1-induced IP formation was not significantly different compared to WKY rats (with the exception of thoracic aorta). We conclude that, at least in SHR and AOB rats, changes in ET-1 signalling are secondary to the elevation in blood pressure.

Animals↗