Biomedical subjects

K Hironaka

Publications and source records attributed to K Hironaka.

At least 19 recordsLinked to original sources

PubMed2001

Percutaneous radiofrequency ablation therapy with combined angiography and computed tomography assistance for patients with hepatocellular carcinoma.

BACKGROUND: Radiofrequency ablation (RFA) for patients with hepatocellular carcinoma (HCC) has been reported previously. This technique is superior to percutaneous microwave coagulation therapy (PMCT) for the enlargement of the necrotic area. Therefore, a few treatment sessions of RFA for patients with small HCC lesions measuring < 3 cm in greatest dimension can achieve complete necrosis. To achieve this with a one-treatment RFA session, the authors designed the technique of RFA with angiography combined with computed tomography (angio-CT) assistance. The advantages of this technique are that it is possible to detect small satellite nodules and to evaluate the real-time therapeutic effect immediately after RFA. METHODS: Ten patients with 12 HCC lesions measuring < 4 cm in greatest dimension underwent RFA with angio-CT assistance. The authors performed standard RFA for six patients (seven tumors) and RFA with balloon occlusion of the hepatic artery (balloon-occluded RFA [BoRFA]) for four patients (five tumors). Final therapeutic efficacy was evaluated with dynamic CT scans performed 2 weeks after treatment. RESULTS: On CT arteriography (CTA) obtained immediately after treatment, a hyperattenuating ring around the nonenhanced region was apparent in all patients. On CT scans obtained 2 weeks after treatment, this ring disappeared, and the greatest dimension of the nonenhanced region was slightly larger than that on the CTA obtained immediately after treatment. The authors achieved complete eradication with one treatment session of RFA in 8 of 10 patients (80%). Local recurrence occurred in one patient 10 months after treatment. The greatest dimension of the area coagulated by BoRFA was significantly larger (greatest long-axis dimension, 38.2 +/- 2.8 mm; greatest short-axis dimension, 35.0 +/- 1.7 mm; n = 5 lesions) than without it (greatest long-axis dimension, 30.0 +/- 4.1 mm; greatest short-axis dimension, 27.0 +/- 4.3 mm; n = 4 lesions; greatest long-axis dimension, P = 0.009; greatest short-axis dimension, P = 0.006). No major complications occurred in any patient. CONCLUSIONS: The authors were able to achieve success with a single treatment session in patients with small HCC using RFA with angio-CT assistance. They consider that RFA with angio-CT assistance is a safe and effective technique for the treatment of patients with small HCC.

Adult↗

PubMed2001

HBV-related fulminant hepatic failure: successful intensive medical therapy in a candidate for liver transplantation.

Fulminant hepatic failure (FHF) usually has a fatal prognosis without liver transplantation. We describe the case of a woman who developed FHF, and was evaluated as a candidate for liver transplantation, but who was cured without transplantation through intensive medical care that included glucagon-insulin therapy, methylprednisolone pulse therapy, interferon beta and lamivudine administration, cyclosporine administration, and high-volume hemodiafiltration and plasma exchange. In a patient with FHF who is a candidate for liver transplantation but for whom the transplantation cannot be performed for some reason, intensive medical therapy, including regeneration-promoting therapy, immunosuppressive therapy, antiviral therapy, and vigorous hepatic support, should be carried out.

Antiviral Agents↗

PubMed2001

A nifedipine coground mixture with sodium deoxycholate. I. Colloidal particle formation and solid-state analysis.

Sodium deoxycholate (DCNa) is a bile salt that forms multimolecular inclusion compounds with a variety of organic substances. In this study, complex formulation of DCNa with nifedipine, a poorly water soluble drug, by grinding was investigated. The coground mixture was prepared with a vibration rod mill, and its solid state was characterized using powder X-ray diffraction, differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) spectroscopy. A laser diffraction particle size analyzer was also used to determine the particle size distribution curve in solution. When a nifedipine-DCNa (1:2 w/w) mixture coground for 30 min was dispersed into water and a pH 6.8 buffer solution, a semitransparent colloidal solution occurred immediately; 90% of the total particles formed in solution had a diameter less than 600 nm. Both powder X-ray diffraction peaks and DSC endothermic peak of nifedipine crystals were not found for the coground mixture, whereas a new exothermic peak was observed on DSC thermograms. The magnitude of this exothermic peak depended on the weight fraction of DCNa and the grinding time, indicating that nifedipine crystals changed into an amorphous state by complex formation with DCNa during the grinding process. In the FTIR spectrum of the coground mixture, the peaks of aromatic CH out-of-plane bend and dihydropyridine NH stretch of nifedipine were considerably weakened, suggesting that van der Waals interaction may be present between the drug and DCNa molecules. From these results, it is clear that the cogrinding method with DCNa is very useful for the formation of amorphous nifedipine in the solid state and the production of colloidal particles of the drug in solution.

Buffers↗

PubMed2001

A nifedipine coground mixture with sodium deoxycholate. II. Dissolution characteristics and stability.

Nifedipine is a poorly water soluble drug that demonstrates low bioavailability. In a previous study, a coground mixture of nifedipine with sodium deoxycholate (DCNa), a bile salt, immediately produced colloidal particles when dispersed in water. In this study, the effect of the weight fraction of DCNa, grinding time, dissolution media, and storage conditions on colloidal particle formation in solution was investigated. The coground mixture was prepared with a vibration rod mill, and its solid state was characterized using powder X-ray diffraction. A laser diffraction particle size analyzer was used to determine the particle size distribution curve in water. The size of particles formed in solution decreased with an increase in the weight fraction of DCNa and grinding time. A nifedipine-DCNa (1:2 w/w) mixture coground for 30 min was used in the experiments. Colloidal particle formation from the coground mixture was also observed in dissolution media of water and a pH 6.8 buffer solution at 37 degrees C. Most precipitates passed through a filter with a pore size of 0.8 microm, but the particle size distribution in water was different from that in the pH 6.8 buffer solution. DCNa exhibited not only micellar solubilization for drug crystals, but also a retarding effect on drug crystal growth in a supersaturated solution. The latter effect could serve to form colloidal particles in solution. When stored under 75% relative humidity at 40 degrees C for 1 month, the amorphous coground mixture crystallized, and the particle size in water markedly increased. Therefore, the weight fraction of DCNa, grinding time, dissolution media, and humidity during storage influence the dissolution characteristics of nifedipine from a coground mixture.

Chromatography, High Pressure Liquid↗

PubMed2000

The protein-tyrosine phosphatase PTPMEG interacts with glutamate receptor delta 2 and epsilon subunits.

Glutamate receptor (GluR) delta2 is selectively expressed in cerebellar Purkinje cells and plays a crucial role in cerebellum-dependent motor learning. Although GluRdelta2 belongs to an ionotropic GluR family, little is known about its pharmacological features and downstream signaling cascade. To study molecular mechanisms underlying GluRdelta2-dependent motor learning, we employed yeast two-hybrid screening to isolate GluRdelta2-interacting molecules and identified protein-tyrosine phosphatase PTPMEG. PTPMEG is a family member of band 4.1 domain-containing protein-tyrosine phosphatases and is expressed prominently in brain. Here, we showed by in situ hybridization analysis that the PTPMEG mRNA was enriched in mouse thalamus and Purkinje cells. We also showed that PTPMEG interacted with GluRdelta2 as well as with N-methyl-d-aspartate receptor GluRepsilon1 in cultured cells and in brain. PTPMEG bound to the putative C-terminal PDZ target sequence of GluRdelta2 and GluRepsilon1 via its PDZ domain. Examination of the effect of PTPMEG on tyrosine phosphorylation of GluRepsilon1 unexpectedly revealed that PTPMEG enhanced Fyn-mediated tyrosine phosphorylation of GluRepsilon1 in its PTPase activity-dependent manner. Thus, we conclude that PTPMEG associates directly with GluRdelta2 and GluRepsilon1. Moreover, our data suggest that PTPMEG plays a role in signaling downstream of the GluRs and/or in regulation of their activities through tyrosine dephosphorylation.

Animals↗

PubMed2000

Cbl suppresses B cell receptor-mediated phospholipase C (PLC)-gamma2 activation by regulating B cell linker protein-PLC-gamma2 binding.

Accumulating evidence indicates that the Cbl protein plays a negative role in immune receptor signaling; however, the mode of Cbl action in B cell receptor (BCR) signaling still remains unclear. DT40 B cells deficient in Cbl showed enhanced BCR-mediated phospholipase C (PLC)-gamma2 activation, thereby leading to increased apoptosis. A possible explanation for the involvement of Cbl in PLC-gamma2 activation was provided by findings that Cbl interacts via its Src homology 2 (SH2) domain with B cell linker protein (BLNK) after BCR ligation. BLNK is a critical adaptor molecule for PLC-gamma2 tyrosine phosphorylation through its binding to the PLC-gamma2 SH2 domains. As a consequence of the interaction between Cbl and BLNK, the BCR-induced recruitment of PLC-gamma2 to BLNK and the subsequent PLC-gamma2 tyrosine phosphorylation were inhibited. Thus, our data suggest that Cbl negatively regulates the PLC-gamma2 pathway by inhibiting the association of PLC-gamma2 with BLNK.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Enhanced interstitial collagenase (matrix metalloproteinase-13) production of Kupffer cell by gadolinium chloride prevents pig serum-induced rat liver fibrosis.

Hepatic fibrosis results from an imbalance between fibrogenesis and fibrolysis in the liver. It remains uninvestigated whether Kupffer cells produce matrix metalloproteinase-13 (MMP-13), which mainly hydrolyzes extracellular matrix (ECM). We sought to determine the role of Kupffer cells in fibrogenesis/fibrolysis. In vivo, we used the rat model of pig serum-induced liver fibrosis. A subset was treated with gadolinium chloride (GdCl(3)), which specifically acts on Kupffer cells. Administration of GdCl(3) remarkably decreased the hydroxyproline content of the liver and increased the expression of MMP-13 mRNA in the liver without a difference in procollagen type I and tissue inhibitors of metalloproteinase-1 (TIMP-1) mRNA expression on Northern blot analysis with the elimination of ED2-positive cells. In vitro, addition of GdCl(3) to isolated Kupffer cells showed increased type I collagen-degrading activity in a dose-dependent manner as well as MMP-13 mRNA expression on Northern blot analysis. It is concluded that Kupffer cells are a major source of MMP-13 and modulation of Kupffer cells by GdCl(3) prevents liver fibrosis with increased expression of MMP-13 mRNA and protein, whereas procollagen type I and TIMP-1 mRNA, which encode two major effectors of fibrogenesis, were unchanged. This is the first report showing that Kupffer cells produce interstitial collagenase (MMP-13) resulting in the reduction of ECM. This discovery may provide new insights into therapy for hepatic fibrosis.

Animals↗

PubMed2000

Loss of inhibitory growth regulation by TGF-beta1 in preneoplastic lesions in rat liver.

Injection of pig serum into rats twice a week for eight weeks induced transforming growth factor-beta1 (TGF-beta1) mRNA expression and protein production resulting in liver fibrosis without parenchymal cell injury. Eight-week treatment with pig serum reduced bromodeoxyuridine (BrdU) -positive hepatocytes 24 hr after 70% partial hepatectomy compared to that in the livers of rats treated with saline for eight weeks. Administration of a choline-deficient L-amino acid-defined (CDAA) diet for six weeks with pig serum coadministration, after pretreatment with pig serum for eight weeks, led to the development of preneoplastic lesions that were positive for the placental form of glutathione S-transferase (GSTP). Eight-week pretreatment with pig serum induced more GSTP-positive lesions and TGF-beta1 mRNA expression and protein concentration in the livers of rats subsequently fed a CDAA diet for six weeks than in rats fed the CDAA diet with saline treatment. These results indicate that TGF-beta1 induced by pig serum treatment inhibited hepatocyte proliferation but failed to prevent the development of preneoplastic lesions in a CDAA diet model.

Animals↗

PubMed2000

Correlation between stellate cell activation and serum fibrosis markers in choline-deficient L-amino acid-defined diet-induced rat liver fibrosis.

The aim of this study was to investigate the association of stellate cell activation with serum fibrosis markers in a rat model of hepatic fibrosis prepared using a choline-deficient L-amino acid (CDAA) defined diet. CDAA diet administration resulted in increased liver hydroxyproline contents in a time-dependent manner with activated stellate cells, expressing alpha-smooth muscle actin (alpha-SMA) as well as increased serum concentrations of amino-terminal procollagen type III peptide (PIIIP) and the 7S fragment of type IV collagen. Hydroxyproline content of the liver showed a closer correlation with the serum 7S (r = 0.75, P < 0.01) concentration than with the serum PIIIP (r = 0.51, P < 0.01) concentration. The percent area of alpha-SMA-positive cells showed stronger correlation with the serum PIIIP concentration (r = 0.85, P < 0.01) than with the 7S concentration (r = 0.50, P < 0.01). These results indicate that the serum PIIIP concentration reflects the activity of fibrogenesis, while the serum 7S concentration reflects the accumulation of collagen fibers in the liver.

Animals↗

PubMed2000

Preventive effect of FK 506 (tacrolimus hydrate) on experimentally induced acute liver injury in rats.

The aim of the study was to investigate the effect of the immunosuppressant FK 506 (tacrolimus hydrate) on acute liver injury induced by Propionibacterium acnes and lipopolysaccharide (LPS). Acute liver injury was induced in male Wistar rats by injecting the animals with P. acnes (10 mg/rat), and administering LPS (10 microg/rat) seven days later. One group was given FK 506 (1 mg/kg) 24 and 2 hr before administration of LPS, and the other group was given the same dose of saline. The 24-hr survival rate, serum alanine aminotransferase (ALT) concentration, and tumor necrosis factor (TNF) -alpha mRNA and protein concentrations in the liver and spleen were then compared. Hepatic macrophages were also isolated from rats seven days after P. acnes injection, LPS, and FK 506 or saline were added to the culture supernatant, and TNF-alpha production was studied. The 24-hr survival rate was 100% in the FK 506-treated group, in contrast with 16.6% in the saline group. Four hours after LPS injection, the serum ALT concentration was 755 +/- 401 in the saline group versus 119 +/- 42 units/ml (P < 0.01) in the FK 506-treated group. The serum TNF-alpha concentration was lower in the FK 506-treated group (1,419 +/- 957 pg/ml) than in the saline group (9205 +/- 2215) (P < 0.01). The mRNA and protein concentrations in the liver and spleen in the two groups did not differ significantly 1 hr after LPS injection but were significantly lower in the FK 506-treated group after 4 hr. FK 506 did not directly inhibit TNF-alpha production by isolated cultured hepatic macrophages. FK 506 is unable to inhibit initial TNF-alpha production by hepatic macrophages (or probably that by splenic macrophages either) stimulated by injection of LPS in P. acnes + LPS-induced acute liver injury. However, the immunosuppressant does limit hepatic damage by inhibiting subsequent aggravation of inflammation by the cytokine network.

Alanine Transaminase↗

PubMed1999

Stimulation of myelin basic protein gene transcription by Fyn tyrosine kinase for myelination.

Myelin is synthesized about the time of birth. The Src-family tyrosine kinase Fyn is involved in the initial events of myelination. Fyn is present in myelin-forming cells and is activated through stimulation of cell surface receptors such as large myelin-associated glycoprotein (L-MAG). Here we show that Fyn stimulates transcription of the myelin basic protein (MBP) gene for myelination. MBP is a major component of the myelin membrane. In 4-week-old Fyn-deficient mice, MBP is significantly reduced, and electron microscopic analysis showed that myelination is delayed, compared with wild-type mice. The Fyn-deficient mice had thinner, more irregular myelin than the wild-type. We found that Fyn stimulates the promoter activity of the MBP gene by approximately sevenfold. The region responsible for the transactivation by Fyn is located between nucleotides -675 and -647 with respect to the transcription start site. Proteins binding to this region were found by gel shift study, and the binding activity correlates with Fyn activity during myelination. These results suggest that transactivation of the MBP gene by Fyn is important for myelination.

Amino Acid Sequence↗

PubMed1999

Prolyl 4-hydroxylase inhibitor (HOE 077) prevents TIMP-1 gene expression in rat liver fibrosis.

The effects of a prolyl 4-hydroxylase inhibitor (HOE 077) on tissue inhibitor of metalloproteinase-1 (TIMP-1) and procollagen type I were examined in rat liver fibrosis. HOE 077 (200 ppm) prevented fibrosis by inhibiting the expression of liver type I procollagen and TIMP-1 mRNAs, with liver hydroxyroline content correlated with the reduction in activated stellate cells. HOE 077 prevents fibrosis by inhibiting proline hydroxylation and stellate cell activation, resulting in reduced expression of procollagen and TIMP-1 mRNAs.

Animals↗

PubMed1999

Iron chelator deferoxamine reduces preneoplastic lesions in liver induced by choline-deficient L-amino acid-defined diet in rats.

The aim of this study was to investigate whether an iron chelator, deferoxamine (DFO) can prevent lipid peroxidation, resulting in reduced liver injury as well as reducing preneoplastic lesions induced by a choline-deficient L-amino acid-defined (CDAA) diet. CDAA diet administration resulted in an increased serum ALT level (367 +/- 58) after two weeks, but simultaneous DFO treatment for two weeks reduced this elevation of ALT as well as malondialdehyde (MDA) production in the liver. Feeding rats a CDAA diet for 12 weeks led to the development of severe liver fibrosis and preneoplastic lesions detected as enzyme-altered lesions. DFO treatment prevented the expression of activated stellate cells, resulting in the reduction of liver fibrosis as well as reducing the development of preneoplastic lesions. These results indicate that iron chelation can reduce the development of preneoplastic lesions in a CDAA diet model.

Alanine Transaminase↗

PubMed1999

Quantitative analysis of liver fibrosis and stellate cell changes in patients with chronic hepatitis C after interferon therapy.

OBJECTIVE: The proliferation and differentiation of stellate (Ito, or fat-storing) cells into myofibroblast-like cells is responsible for the development of liver fibrosis. Using computer image analysis, we evaluated the changes of alpha smooth muscle actin-positive stellate cells and liver fibrosis after interferon-alpha or -beta (IFN-alpha, beta) therapy in patients with chronic hepatitis C. METHODS: Patients with chronic hepatitis C were treated with IFN-alpha or -beta and were divided into three groups on the basis of clinical criteria; a complete responder group (CR, 18 of 51), a partial responder group (PR, 17 to 51), and a nonresponder group (NR, 16 of 51). Liver fibrosis was assessed from specimens stained with Sirius red and was quantitated by computer image analysis. We also evaluated alpha-smooth muscle actin expression in the liver before and after IFN therapy by a semiquantitative scoring method (the alpha-smooth muscle actin index). RESULTS: Before IFN therapy, a large number of stellate cells expressing a-smooth muscle actin were present in the liver biopsy specimens. There was a significant correlation (r = 0.699, p < 0.05) between the change in the percent area of fibrosis and the alpha-smooth muscle actin index before and after IFN therapy in all groups. The complete responder group also showed a significant reduction of a-smooth muscle actin-expressing cells that was correlated with the reduction of serum ALT (r = 0.686, p < 0.05). CONCLUSION: These results suggest a-smooth muscle actin-expressing cells are responsible for liver fibrosis, and the elimination of factors stimulating matrix synthesis (e.g., hepatitis virus) may decrease liver fibrosis.

Actins↗

PubMed1999

High-resolution ultrastructural comparison of renal glomerular and tubular basement membranes.

BACKGROUND/AIMS: Glomerular basement membranes (GBM) and tubular basement membranes (TBM) consist of a fine meshwork composed mainly of type IV collagen. Each segment of tubules has specialized physiologic functions, and thus we investigated the ultrastructure of various basement membranes in rat kidneys. METHODS: Since purifying basement membranes from different tubule segments is technically challenging, we employed tissue negative staining rather than conventional negative staining to compare the ultrastructures of proximal and distal TBM and GBM in normal rats. We also assessed the distribution of extracellular matrix components including type IV collagen, laminin, heparan sulfate proteoglycan, and fibronectin in the basement membranes by immunohistochemistry. RESULTS: TBM and GBM of normal rats showed a fine meshwork structure consisting of fibrils forming small round to oval pores. Short- and long-pore diameters in proximal tubules were 3.3 +/- 0.5 and 3.9 +/- 0.6 nm, respectively, and in distal tubules 3.5 +/- 0.7 and 4.3 +/- 0.8 nm, respectively. For GBM the respective diameters were 2.5 +/- 0.5 and 3.0 +/- 0.5 nm. Immunohistochemical analysis showed no significant difference in distribution of extracellular matrix components between proximal and distal TBM. However, immunofluorescence scores of alpha1 chain of type IV collagen, fibronectin, and laminin were higher in the TBM than in the GBM. On the other hand, heparan sulfate proteoglycan was higher in the GBM. CONCLUSION: Ultrastructural differences in renal basement membranes may be related to differences in physiologic function in each segment.

Animals↗

PubMed1998

Fibrosis accelerates the development of enzyme-altered lesions in the rat liver.

Injection of pig serum into rats twice a week for 8 weeks induced stellate cell activation resulting in liver fibrosis without parenchymal cell injury. Administration of a choline deficient L-amino acid defined (CDAA) diet for 6 weeks with or without pig serum pretreatment led to the development of preneoplastic lesions that were positive for the placental form of glutathione S-transferase (GSTP). Pig serum pretreatment induced more activated stellate cells in the livers of rats subsequently fed a CDAA diet for 6 weeks compared with rats fed the CDAA diet alone. Activated stellate cells were detected as smooth muscle actin (SMA)-positive cells and by the expression of SMA messenger RNA. These cells caused severe fibrosis as assessed by the hepatic hydroxyproline content. Pre-existing fibrosis induced by the activation of stellate cells with pig serum pretreatment increased hepatic malondialdehyde (MDA) level in parallel with GSTP-positive lesions. These results indicate that pre-existing fibrosis with the activated stellate cells accelerates the development of preneoplastic lesions in a CDAA diet model.

Actins↗

PubMed1997

In vivo aortic wall characteristics at the early stage of atherosclerosis in rabbits.

To assess whether vascular responsiveness to alpha-receptor agonist is altered at the early stage of atherosclerosis, in vivo aortic pressure-diameter relationship of the aorta over a wide range of pressures was analyzed before and after the acute administration of alpha-receptor agonist (phenylephrine) in nine hypercholesterolemic fat-fed (7-wk-old) rabbits and eight normal diet-fed (7-wk-old) rabbits. In hypercholesterolemic fat-fed rabbits, there was no major structural change in the aortic wall except fatty streak, despite a marked increase in the level of plasma cholesterol, indicating the early stage of atherosclerosis of the aorta. By using a modified three-element Maxwell model, diastolic stress-strain relationship was computed after applying several assumptions to the actual aortic pressure-diameter relationship. After the intravenous administration of phenylephrine at a rate of 5 micrograms.kg-1.min-1, the stress (ordinate)-strain (abscissa) relationship curves were shifted to the left, indicating the activation of aortic smooth muscle by phenylephrine. The difference between the stress before and after phenylephrine showed a single peak at a certain strain. The peak difference in the stress was smaller in hypercholesterolemic fat-fed rabbits than in normal diet-fed rabbits, indicating the reduction of vascular responsiveness at the early stage of atherosclerosis of the aorta.

Adrenergic alpha-Agonists↗

PubMed1997

Dose-dependent effect of ANG II-receptor antagonist on myocyte remodeling in rat cardiac hypertrophy.

The goal of this study was to examine the effect of an angiotensin II type 1 (AT1)-receptor antagonist (TCV-116) on left ventricular (LV) geometry and function during the development of pressure-overload LV hypertrophy. A low (LD; 0.3 mg x kg(-1) x day(-1)) or a high (HD; 3.0 mg x kg(-1) x day(-1)) dose of TCV-116 was administered to abdominal aortic-banded rats over 4 wk, and hemodynamics and morphology were then evaluated. In both LD and HD groups, peak LV pressures were decreased to a similar extent compared with the vehicle-treated group but stayed at higher levels than in the sham-operated group. In the LD group, both end-diastolic wall thickness (3.08 +/- 0.14 mm) and myocyte width (13.3 +/- 0.1 microm) decreased compared with those in the vehicle-treated group (3.67 +/- 0.19 mm and 15.3 +/- 0.1 microm, respectively; both P < 0.05). In the HD group, myocyte length was further decreased (HD: 82.6 +/- 2.6, LD: 94.1 +/- 2.9 microm; P < 0.05) in association with a reduction in LV midwall radius (HD: 3.36 +/- 0.12, LD: 3.60 +/- 0.14 mm; P < 0.05) and peak midwall fiber stress (HD: 69 +/- 8, LD: 83 +/- 10 x 10(3) dyn/cm2; P < 0.05). There was no significant difference in cardiac output among all groups. The AT1-receptor antagonist TCV-116 induced an inhibition of the development of pressure-overload hypertrophy. Morphologically, not only the width but also the length of myocytes was attenuated with TCV-116, leading to a reduction of midwall radius and hence wall stress, which in turn may contribute to a preservation of cardiac output.

Angiotensin Receptor Antagonists↗