Formate-producing capacity provided by reducing ability of Streptococcus thermophilus nicotinamide adenine dinucleotide oxidase determines yogurt acidification rate.

Yogurt is made by fermenting milk with 2 lactic acid bacteria, Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus. To comprehensively understand the protocooperation mechanism between S. thermophilus and L. bulgaricus in yogurt fermentation, we examined 24 combinations of cocultures comprising 7 fast- or slow-acidifying S. thermophilus strains with 6 fast- or slow-acidifying L. bulgaricus strains. Furthermore, 3 NADH oxidase (Nox)-deficient mutants (Δnox) and one pyruvate formate-lyase deficient mutant (ΔpflB) of S. thermophilus were used to evaluate the factor that determines the acidification rate of S. thermophilus. The results revealed that the acidification rate of S. thermophilus monoculture determined the yogurt fermentation rates, despite the coexistence of L. bulgaricus, whose acidification rate was either fast or slow. Significant correlation was found between the acidification rate of S. thermophilus monoculture and the amount of formate production. Result using ΔpflB showed that the formate was indispensable for the acidification of S. thermophilus. Moreover, results of the Δnox experiments revealed that formate production required Nox activity, which not only regulated dissolved oxygen, but also the redox potential. The Nox provided the large decrease in redox potential required by pyruvate formate-lyase to produce formate. A highly significant correlation was found between formate accumulation and Nox activity in S. thermophilus. In conclusion, the formate production ability provided by the action of Nox activity determines the acidification rate of S. thermophilus, and consequently, regulates yogurt coculture fermentation.

Long-term outcomes of hemostatic therapy for variceal bleeding and the challenge pending in the post-direct-acting antivirals era.

Background and study aims: This study evaluated the longterm outcomes of mainly endoscopic hemostatic therapy for gastrointestinal variceal bleeding and of the transition of hemostatic therapy. Patients and methods: Among 1,163 patients treated for gastrointestinal varices between April 2006 and June 2020, a total of 125 patients who underwent emergency hemostatic therapy were enrolled. Survival rates and secondary evaluation points were analyzed. Additionally, patients were classified into two groups: the previous and latter term. Patients' background, therapeutic method, and treatment results were compared between the groups. Results: 94.4% had cirrhosis. The average Child-Pugh score was 8.90. Successful primary hemostasis rate was 98.4%, and 5.6% died within 2 weeks, all with a Child-Pugh score ≥9. The respective 1- and 5-year survival rates for Child-Pugh grade A/B were 81.3% and 55.4%, while those for Child-Pugh grade C were 58.1% and 17.8%. Child-Pugh grade C or hepatocellular carcinoma was significantly associated with poor prognosis. In total, 21.6% experienced variceal re-bleeding; 62.9% of these cases were triggered by continued alcohol consumption. There was no significant difference in survival between patients with and without variceal re-bleeding and in post-treatment survival between the previous and latter terms. In the latter term, the number of cases caused by continued alcohol consumption significantly increased. Conclusions: Multidisciplinary treatment and continuation of proper management after hemostatic therapy for variceal bleeding are crucial. Continued alcohol consumption leads to variceal bleeding and re-bleeding; its proper management, including alcohol abstinence, is one of the major challenges left in the post-directacting antivirals era.

The critical role of urease in yogurt fermentation with various combinations of Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus.

The protocooperation between Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus relies on metabolite exchanges that accelerate acidification during yogurt fermentation. Conflicting results have been obtained in terms of the effect of the Strep. thermophilus urease and the NH3 and CO2 that it generates on the rate of acidification in yogurt fermentation. It is difficult to perform a systematic study of the effects of urease on protocooperation because it is necessary to distinguish among the direct, indirect, and strain-specific effects resulting from the combination of the strains of both species. To evaluate the direct effects of urease on protocooperation, we generated 3 urease-deficient mutants (ΔureC) of fast- and slow-acidifying Strep. thermophilus strains and observed the effects of NH3 or CO2 supplementation on acidification by the ΔureC strains. Further, we examined 5 combinations of 3 urease-deficient ΔureC strains with 2 CO2-responsive or CO2-unresponsive strains of L. bulgaricus. Urease deficiency induced a shortage of ammonia nitrogen and CO2 for the fast- and slow-acidifying Strep. thermophilus and for the CO2-responsive L. bulgaricus, respectively. Notably, the shortage of ammonia nitrogen had more severe effects than that of CO2 on yogurt fermentation, even if coculture with L. bulgaricus masked the effect of urease deficiency. Our work established (1) that urease deficiency inhibits the fermentative acceleration of protocooperation regardless of the Strep. thermophilus and L. bulgaricus strain combinations, and (2) that urease is an essential factor for effective yogurt acidification.

Photofunctionalised Ti6Al4V implants enhance early phase osseointegration.

OBJECTIVES: Ultraviolet (UV) light-mediated photofunctionalisation is known to improve osseointegration of pure titanium (Ti). However, histological examination of titanium alloy (Ti6Al4V), which is frequently applied in orthopaedic and dental surgery, has not yet been performed. This study examined the osseointegration of photofunctionalised Ti6Al4V implants. METHODS: Ti and Ti6Al4V implants were treated with UV light, and the chemical composition and contact angle on the surfaces were evaluated to confirm photofunctionalisation. The implants were inserted into femurs in rats, and the rats were killed two or four weeks after the surgery. For histomorphometric analysis, both the bone-implant contact (BIC) ratio and the bone volume (BV) ratio were calculated from histological analysis and microcomputed tomography data. RESULTS: The amount of carbon and the contact angle on both implants were significantly reduced after UV irradiation. The BIC ratios for both UV light-treated implants significantly increased at two weeks, but there was no significant difference at four weeks. There was no significant difference in the BV ratios between the UV light-treated and control implants at two or four weeks. CONCLUSIONS: This study suggests that photofunctionalisation of Ti6Al4V implants, similar to that of Ti implants, may promotes osseointegration in early but not in the late phase of osseointegration.Cite this article: R. Yamauchi, T. Itabashi, K. Wada, T. Tanaka, G. Kumagai, Y. Ishibashi. Photofunctionalised Ti6Al4V implants enhance early phase osseointegration. Bone Joint Res 2017;6:331-336. DOI: 10.1302/2046-3758.65.BJR-2016-0221.R1.

Bactericidal and antimicrobial effects of pure titanium and titanium alloy treated with short-term, low-energy UV irradiation.

OBJECTIVES: The surface of pure titanium (Ti) shows decreased histocompatibility over time; this phenomenon is known as biological ageing. UV irradiation enables the reversal of biological ageing through photofunctionalisation, a physicochemical alteration of the titanium surface. Ti implants are sterilised by UV irradiation in dental surgery. However, orthopaedic biomaterials are usually composed of the alloy Ti6Al4V, for which the antibacterial effects of UV irradiation are unconfirmed. Here we evaluated the bactericidal and antimicrobial effects of treating Ti and Ti6Al4V with UV irradiation of a lower and briefer dose than previously reported, for applications in implant surgery. MATERIALS AND METHODS: Ti and Ti6Al4V disks were prepared. To evaluate the bactericidal effect of UV irradiation, Staphylococcus aureus 834 suspension was seeded onto the disks, which were then exposed to UV light for 15 minutes at a dose of 9 J/cm2. To evaluate the antimicrobial activity of UV irradiation, bacterial suspensions were seeded onto the disks 0, 0.5, one, six, 24 and 48 hours, and three and seven days after UV irradiation as described above. In both experiments, the bacteria were then harvested, cultured, and the number of colonies were counted. RESULTS: No colonies were observed when UV irradiation was performed after the bacteria were added to the disks. When the bacteria were seeded after UV irradiation, the amount of surviving bacteria on the Ti and Ti6Al4V disks decreased at 0 hours and then gradually increased. However, the antimicrobial activity was maintained for seven days after UV irradiation. CONCLUSION: Antimicrobial activity was induced for seven days after UV irradiation on both types of disk. Irradiated Ti6Al4V and Ti had similar antimicrobial properties.Cite this article: T. Itabashi, K. Narita, A. Ono, K. Wada, T. Tanaka, G. Kumagai, R. Yamauchi, A. Nakane, Y. Ishibashi. Bactericidal and antimicrobial effects of pure titanium and titanium alloy treated with short-term, low-energy UV irradiation. Bone Joint Res 2017;6:108-112. DOI: 10.1302/2046-3758.62.2000619.

Reactions of (+)-catechin with salivary nitrite and thiocyanate under conditions simulating the gastric lumen: production of dinitrosocatechin and its thiocyanate conjugate.

Catechins are ingested as food components and supplements. It is known that catechins are transformed to dinitrosocatechins by nitrite under acidic conditions, suggesting the possibility of their formation in the stomach because saliva contains nitrite. This paper deals with nitrite-induced transformation of (+)-catechin in methanol extracts of adzuki bean into 6,8-dinitrosocatechin in acidified saliva (pH ≈ 1.9). As the mechanism of its formation, addition of nitric oxide (NO) to (+)-catechin semiquinone radical, both of which were produced in nitrous acid/(+)-catechin systems, was proposed. The dinitrosocatechin was oxidized to the quinone by nitrous acid, and the quinone reacted with a salivary component thiocyanate producing 6'-thiocyanato-6,8-dinitrosocatechin. Since quinones are toxic, we propose a function of thiocyanate as a scavenger of the o-quinone formed from dinitrosocatechins in the stomach.

Virus activation and immune function during intense training in rugby football players.

Epidemiological studies suggest that highly trained athletes are more susceptible to upper respiratory tract infections (URTI) compared with the general population. Upper respiratory symptoms (URS) often appear as either primary invasion of pathogenic organisms and/or reactivation of latent viruses such as Epstein-Barr virus (EBV). The purpose of this study was to examine the relationship between EBV reactivation and the appearance of URS during intensive training in collegiate rugby football players. We evaluated EBV-DNA expression in saliva and examined the relationship between onset of URS and daily changes in EBV-DNA as well as secretory immunoglobulin A (SIgA) levels among 32 male collegiate rugby football players during a 1-month training camp. The EBV-DNA expression tended to be higher in subjects who exhibited sore throat (p=0.07) and cough (p=0.18) than that of those who had no symptoms, although their differences were not significant. The SIgA level was significantly lower 1 day before the EBV-DNA expression (p<0.05). The number of URS increased along with the EBV-DNA expression and decrease of SIgA levels. These results suggest that the appearance of URS is associated with reactivation of EBV and reduction of SIgA during training.

Exercise in, and adaptations to a cold environment have no effect on SIgA.

AIM: The authors hypothesized that inconsistent SIgA response to exercise is caused by the different adaptative status of subjects to a cold environment. The purposes of the study were to examine whether moderate-intense exercise in a cold environment decreases SIgA and whether adaptation to a cold environment has any effect on SIgA. METHODS: Young male skaters, short track (N=9) and inline (N=10), participated in this study. All subjects cycled for 60 min at 65% VO(2max) in cold (ambient temperature: 5 +or - 1 degrees Celsius, relative humidity 41 + or - 9%) and thermoneutral (ambient temperature: 21 + or - 1 degrees Celsius, relative humidity 35 + or - 5%) conditions. Saliva samples were collected as follows: before and after 1hour of environmental exposure; immediately, 30-min, 60-min and 120-min after the exercise. RESULTS AND CONCLUSIONS: Salivary SIgA and saliva flow rate decreased after the exercise in both groups only in thermoneutral conditions. The SIgA secretion rate did not decrease after moderate-high intensity exercise in a cold environment, and the SIgA response to exercise was not affected by the different adaptative status of subjects to the cold environment.

Association analyses between genetic polymorphisms of endothelial nitric oxide synthase gene and hypertension in Japanese: The Suita Study.

OBJECTIVES: Endothelium-derived nitric oxide plays a key role in the regulation of vascular tone. Recently, endothelial nitric oxide synthase (eNOS) gene polymorphisms were reported to be associated with hypertension or coronary spasm. We investigated the association between the eNOS gene polymorphisms and hypertension in a large population-based sample of 4055 Japanese. DESIGN AND METHODS: We investigated two polymorphisms of the eNOS gene, Glu298Asp polymorphism of exon 7 and T(-786)C polymorphism of the promoter region. The genotype distribution in hypertensive subjects was compared to that in the other subjects. The influence of the genotype on blood pressure values was analyzed in the subjects not taking hypertensive medication. The promoter activities of the eNOS gene with the (-786)T or (-786)C allele were measured by a luciferase reporter gene assay. RESULTS: There was significant linkage disequilibrium between the two polymorphisms (P < 0.0001). The genotype distribution of the Glu298Asp or T(-786)C polymorphism did not differ between the hypertensive and the other subjects. No significant differences in the blood pressure of subjects not taking hypertensive medication were observed among the three genotypes of Glu298Asp or T(-786)C polymorphisms. No significant differences in the promoter activity were observed between bovine endothelial cells transfected with the (-786)T and (-786)C alleles. CONCLUSIONS: Our data suggested that these polymorphisms of the eNOS gene are unlikely to be major factors in the susceptibility to hypertension in the Japanese population studied.

Structural features of arabinogalactan-proteins from the fruit of Lycium chinense Mill.

In addition to the other arabinogalactan-proteins (AGPs) (Cp-1-C and -D) already reported, two kinds of AGP (Cp-2-B and Hp-2-C) were obtained from the fruit of Lycium chinense Mill. The ratio of arabinose to galactose was approximately 1:1 in both samples, and the carbohydrate was linked O-glycosidically to serine in Cp-2-B, and to both serine and threonine residues of the protein in Hp-2-C. The weight-average molecular weight was 71,000 for Cp-2-B and 120,000 for Hp-2-C. Both samples also contained non-reducing terminal 3-O- and 4-O-substituted galacturonic acids. The ratio of 6-O-substituted galactose (linear part) and 3,6-di-O-substituted galactose (branching point) was almost unity in both samples, being obviously different from the case of Cp-1-C (predominant in the branching domain) and Cp-1-D (predominant in the linear domain). These results offer fresh insight into the grouping of the AGPs, based on the ratio of 6-O- and 3,6-di-O-substituted galactosyl residues.

Effects of omeprazole and pirenzepine on enterochromaffin-like cells and parietal cells in rat stomach.

PURPOSE: The purpose of this study was to investigate the mechanism of the regulation of histamine synthesis in enterochromaffin-like cells, chemically and structurally, by treatment with omeprazole and pirenzepine. METHODS: The ultrastructures of enterochromaffin-like cells and parietal cells were examined in rats treated with oral omeprazole (20 mg/kg) or intraperitoneal pirenzepine (1 mg/kg) administration. Serum gastrin concentrations, mRNA levels of H+-K+-ATPase and histidine decarboxylase, and the fundic concentrations of somatostatin and histamine were determined. RESULTS: Pirenzepine treatment suppressed omeprazole-induced increases in serum gastrin levels and mRNA levels of H+-K+-ATPase and histidine decarboxylase. Pirenzepine also decreased omeprazole-induced increases of histamine concentration in fundic mucosa. Pirenzepine elevated somatostatin mRNA level, previously decreased by omeprazole treatment, in fundic mucosa. In the cytoplasm of enterochromaffin-like cells, omeprazole markedly reduced the numbers of vesicles and granules, but significantly increased their diameters, whereas pirenzepine treatment changed neither of these features. The densities and diameters of both vesicles and granules produced by treatment with omeprazole and pirenzepine were between those produced by treatment with omeprazole alone and pirenzepine alone. CONCLUSIONS: Omeprazole-induced hypergastrinemia and pirenzepine-induced somatostatin synthesis play important roles not only in histamine synthesis but also in ultrastructural changes in enterochromaffin-like cells.

Analysis of molecular species of glycolipids in fruit pastes of red bell pepper (Capsicum annuum L.) by high-performance liquid chromatography-mass spectrometry.

Five major glycolipid classes (acylated steryl glucoside, steryl glucoside, monogalactosyldiacylglycerol, digalactosyldiacylglycerol, and glucocerebroside) from fruit pastes of red bell pepper were separated by silica gel column chromatography. The molecular species of each glycolipid were separated and characterized by reversed-phase high-performance liquid chromatography coupled with on-line mass spectrometry using atmospheric pressure chemical ionization. The molecular species of steryl glucoside were beta-sitosteryl and campesteryl glucosides, and those of the acylated steryl glucoside were their fatty acid esters. The dilinolenoyl species was predominant in monogalactosyldiacylglycerol in addition to small amounts of another five molecular species, whereas digalactosyldiacylglycerol consisted of seven molecular species varying in their degree of unsaturation. The glucocerebroside class contained at least seven molecular species, which were characterized by proton nuclear magnetic resonance spectroscopy.

Design, syntheses, and structure-activity relationships of indan derivatives as endothelin antagonists; new lead generation of non-peptidic antagonist from peptidic leads.

A new lead generation of non-peptidic ET(A) antagonists from two peptidic ET(A)-selective ones, BQ-123 and FR139317, was performed. Using computer assisted molecular modeling, a putative pharmacophore was constructed from the superposition of the reported three-dimensional structure of the cyclic peptide BQ-123 and a presumable beta-turn active conformation of the linear peptide FR139317 formed by an intramolecular hydrogen bond. According to this model, a new series of indan derivatives were designed and synthesized. Among these, 5-isobutyrylamino-6-(1-naphthylmethyloxy)-3-(2-thienyl)-1-indancarboxylic acid (1b) showed a moderate ET(A) antagonistic activity (IC50 = 28 microM).

Bioactive peptides derived from food proteins preventing lifestyle-related diseases.

Many kinds of bioactive peptides which might prevent lifestyle-related diseases are released from food proteins after enzymatic digestion. Inhibitory peptides for angiotensin I-converting enzyme (ACE) having anti-hypertensive effect have been isolated from enzymatic digests of various food proteins. LKPNM, which was isolated from the thermolysin digest of dried bonito was activated 8-fold by ACE itself and showed a prolonged effect after oral administration. Two vasorelaxing peptides, ovokinin and ovokinin(2-7), showing antihypertensive effect after oral administration were obtained from ovalbumin digests. We found that low molecular weight peptides derived from food proteins lowered serum cholesterol without increasing excretion of cholesterol and bile acids. An immunostimulating peptide isolated from an enzymatic digest of soybean protein prevented alopecia induced by cancer chemotherapy.

Analysis of the addition products of alpha-tocopherol with phosphatidylcholine-peroxyl radicals by high-performance liquid chromatography with chemiluminescent detection.

A chemiluminescence-based high-performance liquid chromatographic method was developed for the analysis of the addition products of alpha-tocopherol with phosphatidylcholine-peroxyl radicals (TOO-PC). The TOO-PC eluted from a reversed-phase column was reacted with a chemiluminescent reagent consisting of a Cypridina luciferin analog and a lipid-soluble iron chelate in acidic methanol at 50 degrees C, and the generated chemiluminescence was monitored. The detection limit for TOO-PC by this method was about 1 pmol. This method was applied to the detection of TOO-PC in the peroxidized membranes prepared from rabbit erythrocyte ghosts. When the erythrocyte ghosts were peroxidized by the addition of a water-soluble free radical initiator, a peak corresponding to TOO-PC was detected on the chromatogram with chemiluminescent detection. The amount of TOO-PC in the erythrocyte membranes increased with the depletion of endogenous alpha-tocopherol. The results indicate that this method proved useful for the detection of the TOO-PC formed by the peroxyl-radical scavenging reactions of alpha-tocopherol in biological systems.

Synthesis of 5-hydroxy-2-(beta-D-ribofuranosyl)pyran-4-one from a pyranulose glycoside.

The synthesis of 5-hydroxy-2-(beta-D-ribofuranosyl)pyran-4-one (9) is described. Treatment of pyranulose glycoside with bromine in carbon tetrachloride afforded brompyranulose glycoside in 90% yield. The reaction of (6S)- and (6R)-4-bromo-6-hydroxy-6-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-6H- pyran-3-one (2) in acidic media was examined with the following results: the reaction of 2 with trifluoroacetic acid (TFA) in dioxane afforded a mixture of 5-hydroxy-2-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)pyran-4-one (3) and its furan derivative 5-hydroxy-2-{5-(benzoyloxy)methyl]furan-2-yl}pyran-4-one (4), but the use of hydrochloric acid formed the bromofurfural, 3-bromo-5-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-2-furancarboxyal dehyde only. Acetylation of a mixture (3 and 4) with acetic anhydride facilitated product separation to give the corresponding acetates 5-acetoxy-2-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)pyran-4-one (5) and 5-acetoxy-2-{5-[(benzoyloxy)methyl]furan-2-yl}pyran-4-one (6). Treatment of 5 with hydrazine afforded 3-hydroxymethyl-6-(beta-D-ribofuranosyl)-1H-pyridazin-4-one in 43% yield. Debenzoylation of 5 with aq ammonia gave 9 in 50% yield.

Pharmacological profile of T-0201, a highly potent and orally active endothelin receptor antagonist.

The authors studied the pharmacological properties of N-(6-(2-(5-bromopyrimidin-4-yl)-4-(2-hydroxy-1, 1-dimethylethyl)benzensulfonamide sodium salt sesquihydrate (T-0201), a new nonpeptide endothelin (ET) receptor antagonist, in vitro and in vivo. In binding studies, T-0201 competitively antagonized the specific binding of [125I]-ET-1 to human cloned ETA receptors (the Ki value was 0.015 +/- 0.004 nM). T-0201 weakly inhibited [125I]-ET-1-binding to human cloned ETB receptors; the Ki value was 41 +/- 21 nM. T-0201 shifted the concentration-response curve of ET-1-induced contraction of the isolated rat aorta (ETA receptors) to the right (pA2 = 9.0 +/- 0.2). In the isolated rat trachea, a selective ETB agonist sarafotoxin S6c-induced contraction was inhibited by T-0201 (pA2 = 6.8 +/- 0.3). T-0201 also caused the inhibition of ET-1-induced contraction of the isolated rabbit pulmonary artery (pA2 = 5.7 +/- 0.3). In anesthetized rats, T-0201 (0.01-1 mg/kg) inhibited the pressor response to exogenous big ET-1 (1 nmol/kg i.v.), after both i.v. and p.o. administration, in a dose-dependent manner. The significant inhibitory effect of orally administered T-0201 on big ET-1-induced pressor response lasted for 4 hr at 0.1 mg/kg and for 8 hr at 1 mg/kg. Thus the present study demonstrates that T-0201 is a highly potent, long-lasting, orally active and selective ETA receptor antagonist.

Preparation and characterization of 8a-(phosphatidylcholine-dioxy)-alpha-tocopherones and their formation during the peroxidation of phosphatidylcholine in liposomes.

alpha-Tocopherol was reacted with the phosphatidylcholines (PCs), 1-palmitoyl-2-linoleoyl-3-sn-PC (PLPC), 1-palmitoyl-2-linolenoyl-3-sn-PC, 1-palmitoyl-2-arachidonoyl-3-sn-PC (PAPC) and 1-stearoyl-2-arachidonoyl-3-sn-PC, in the presence of the free radical initiator, 2,2'-azobis (2,4-dimethylvaleronitrile), at 37 degrees C. The addition products of alpha-tocopherol with the PC peroxyl radicals were isolated and identified as 8a-(PC-dioxy)-alpha-tocopherones, in which the peroxyl radicals derived from each PC molecule attacked the 8a-position of the alpha-tocopheroxyl radical. The antioxidative efficiency of alpha-tocopherol against the peroxidation of PLPC and PAPC in liposomes was assessed by the formation of the reaction products of alpha-tocopherol. When alpha-tocopherol was oxidized in the presence of the water-soluble free radical initiator, 2,2'-azobis (2-amidinopropane) dihydrochloride, epoxy-alpha-tocopherylquinones were mainly produced together with 8a-(PC-dioxy)-alpha-tocopherones and alpha-tocopherylquinone. The yield of alpha-tocopherylquinone was increased by treating each sample with dilute acid which indicates the presence of tocopherone precursors other than the 8a-(PC-dioxy)-alpha-tocopherones. The same products were also detected from iron-dependent peroxidation, although the yields were very low.

Cloning of hamster preproendothelin-1 cDNA and its expression in the heart.

To elucidate the pathophysiologic roles of endothelin-1 (ET-1) in the heart, we first cloned and sequenced a part of hamster preproET-1 cDNA from the heart of the CHF146 hamsters. The amino acid sequence has 89% homology to that of rat preproET-1 in the cloned part. The deduced hamster 21-residue mature ET-1 is identical to human, rat, canine, and mouse ET-1. In the next step we investigated the expression of preproET-1 mRNA in the failing heart of CHF146 hamsters. For this purpose, we used 46-week-old CHF146 hamsters and age-matched control healthy hamsters. Left ventricular (LV) + dP/dtmax was significantly lower in CHF146 hamsters than in control hamsters. LV end-diastolic pressure was significantly higher in CHF146 hamsters than in control hamsters, as was central venous pressure. These results suggested that the CHF146 hamsters developed congestive heart failure. The expression of preproET-1 mRNA was greatly enhanced in the LV of the CHF146 hamsters. Because it has been reported that ET-1 induces cardiac hypertrophy and injury to cardiac myocytes in addition to its potent positive inotropic and chronotropic actions, the present findings suggest that endogenous ET-1 plays pathophysiologic roles in the failing heart of CHF146 hamsters.