研究等業績 - 原著論文 - 渡邊 博之
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Modified autonomic regulation in mice mutated in the β4 subunit of the lh/lh calcium channel.
Manabu Murakami, Takashi Suzuki, Tsai-Wen Wu, Kenji Kuwasako, Eiki Takahashi, Hiroyuki Watanabe, Agnieszka M Murakami, Ichiro Miyoshi, Teruyuki Yanagisawa, Hironobu Sasano, Kyoichi Ono, Takayoshi Ohba
Biochemical and biophysical research communications 461 ( 2 ) 200 - 5 2015年05月 [査読有り]
研究論文（学術雑誌）
Genetic analyses have revealed an important association between P/Q-type calcium channel activities and hereditary neurological disorders. The P/Q-type channels are composed principally of heterologous multimeric subunits including CaV2.1 and CaVβ4. Of these, the β4 subunit is thought to play a significant role in channel physiology, because a mouse line mutant in that subunit (the lethargic mouse: lh) exhibits a severe ataxic phenotype. The aim of the present study was to elucidate the physiological importance of the β4 subunit. ECG analysis showed that the T wave was high in 8-week-old lh mutants; this may be associated with hyperkalemia. Upon pharmacological ECG analysis, 2-3-week-old lh mutants exhibited reduced responses to a β-blocker and a muscarinic receptor antagonist. Analysis of heart rate variability revealed that the R-R interval was unstable in lh mutants and that both the low- and high-frequency components had increased in extent, indicating that the tonus of both the sympathetic and parasympathetic nervous systems was modified. Thus, our present study revealed that the β4 subunit played a significant role in regulation of sympathetic and parasympathetic nerve activities.
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Beneficial effects of adaptive servo-ventilation therapy on albuminuria in patients with heart failure.
Yoshikazu Tamura, Takashi Koyama, Hiroyuki Watanabe, Tomoki Hosoya, Hiroshi Ito
Journal of cardiology 65 ( 5 ) 412 - 7 2015年05月 [査読有り]
研究論文（学術雑誌）
BACKGROUND: Short-duration adaptive servo-ventilation (ASV) therapy can be effective for heart failure (HF) patients. Albuminuria is recognized as a prognostic marker for HF. We investigated whether short-duration and short-term ASV therapy reduced albuminuria in HF patients. METHODS AND RESULTS: Twenty-one consecutive HF patients were divided into two groups: those who tolerated ASV therapy (ASV group, n=14) and those who did not (non-ASV group, n=7). ASV therapy was administered to enrolled patients for 1 week for 2h per day (1h in the morning and 1h in the afternoon). The urinary albumin to creatinine ratio (UACR), urinary 24h norepinephrine (NE) excretion, high-sensitivity C-reactive protein (hs-CRP), and plasma brain natriuretic peptide (BNP) levels were measured before and 1 week after ASV therapy. In the ASV group, but not the non-ASV group, the UACR significantly decreased, together with a decrease in urinary NE and hs-CRP levels. There were significant correlations between the changes in UACR and hs-CRP and between the changes in urinary NE and hs-CRP. Multiple linear regression analyses indicated that ASV use was the strongest predictor of decreased UACR. CONCLUSION: Albuminuria, urinary NE, and hs-CRP levels reduced in HF patients who could receive short-duration and short-term ASV therapy. Anti-inflammatory effects of ASV therapy may partly mediate the reduction of albuminuria.
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Obstructed bi-leaflet prosthetic mitral valve imaging with real-time three-dimensional transesophageal echocardiography.
Mai Shimbo, Hiroyuki Watanabe, Shunsuke Kimura, Mai Terada, Takako Iino, Kenji Iino, Hiroshi Ito
Journal of clinical ultrasound : JCU 43 ( 1 ) 64 - 7 2015年01月 [査読有り]
研究論文（学術雑誌）
Real-time three-dimensional transesophageal echocardiography (RT3D-TEE) can provide unique visualization and better understanding of the relationship among cardiac structures. Here, we report the case of an 85-year-old woman with an obstructed mitral prosthetic valve diagnosed promptly by RT3D-TEE, which clearly showed a leaflet stuck in the closed position. The opening and closing angles of the valve leaflets measured by RT3D-TEE were compatible with those measured by fluoroscopy. Moreover, RT3D-TEE revealed, in the ring of the prosthetic valve, thrombi that were not visible on fluoroscopy. RT3D-TEE might be a valuable diagnostic technique for prosthetic mitral valve thrombosis.
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Apnea during Cheyne-Stokes-like breathing detected by a piezoelectric sensor for screening of sleep disordered breathing
Takashi Koyama, Shinichi Sato, Takashi Kanbayashi, Hideaki Kondo, Hiroyuki Watanabe, Seiji Nishino, Tetsuo Shimizu, Hiroshi Ito, Kyoichi Ono
SLEEP AND BIOLOGICAL RHYTHMS 13 ( 1 ) 57 - 67 2015年01月 [査読有り]
研究論文（学術雑誌）
A simplified diagnostic/monitoring instrument for use in primary screening for sleep-disordered breathing (SDB) has been desired. This study was designed to assess the validity of a newly developed piezoelectric sensor as a simple and noninvasive tool for primary screening for sleep-disordered breathing. Forty-three consecutive patients suspected of having sleep-disordered breathing and 10 healthy volunteers were enrolled. Breathing movement was detected with the piezoelectric sensor (180 × 30 × 1 mm), which was placed under a bed sheet under patients, and simultaneous polysomnographic recordings were obtained. We counted the number of apneas of >10 s, irrespective of central or obstructive, that appeared during Cheyne-Stokes-like breathing with a waxing and waning pattern with an amplitude ratio of >10 in the piezoelectric sensor signal. The correlation coefficient between the number of apneas and apnea–hypopnea index (AHI) was 0.74 (P < 0.0001). The sensitivity/specificity of the number of apneas for distinguishing non-SDB patients from mild SDB patients (AHI ≥ 5) were 92.1/60.0% and those for separating moderate to severe (AHI ≥ 15) and severe (AHI ≥ 30) SDB patients from the other patients were 96.9/100% and 93.8/86.5%, respectively. There were no complaints from patients about the use of the piezoelectric sensor. The results indicate that the number of apneas detected by this piezoelectric sensor during Cheyne-Stokes-like breathing is a potential new index for primary screening for SDB at least for cardiac patients. Thus, the piezoelectric-sensor system might be useful for simple, noninvasive and comfortable SDB screening at home, hospitals and health care facilities.
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Subclinical microalbuminuria as a predictor of heart failure prognosis.
Hiroyuki Watanabe, Kenji Iino, Hiroshi Ito
Circulation journal : official journal of the Japanese Circulation Society 78 ( 12 ) 2838 - 9 2014年12月 [査読有り]
研究論文（学術雑誌）
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Morning pentraxin3 levels reflect obstructive sleep apnea-related acute inflammation.
Yusuke Kobukai, Takashi Koyama, Hiroyuki Watanabe, Hiroshi Ito
Journal of applied physiology (Bethesda, Md. : 1985) 117 ( 10 ) 1141 - 8 2014年11月 [査読有り]
研究論文（学術雑誌）
This study investigated morning levels of pentraxin3 (PTX3) as a sensitive biomarker for acute inflammation in patients with obstructive sleep apnea (OSA). A total of 61 consecutive patients with OSA were divided into two groups: non-to-mild (n = 20) and moderate-to-severe (n = 41) OSA based on their apnea-hypopnea index (AHI) score. Those patients with moderate-to-severe OSA were further divided into continuous positive airway pressure (CPAP) treated (n = 21) and non-CPAP-treated (n = 20) groups. Morning and evening serum PTX3 and high-sensitivity (hs) C-reactive protein (CRP) levels were measured before and after 3 mo of CPAP therapy. The baseline hs-CRP and PTX3 levels were higher in patients with moderate-to-severe OSA than in those with non-to-mild OSA. Moreover, the serum PTX3 levels, but not the hs-CRP levels, were significantly higher after than before sleep in the moderate-to-severe OSA group (morning PTX3, 1.96 ± 0.52; evening PTX3, 1.71 ± 0.44 ng/ml). OSA severity as judged using the AHI was significantly correlated with serum PTX3 levels but not hs-CRP levels. The highest level of correlation was found between the AHI and morning PTX3 levels (r = 0.563, P < 0.001). CPAP therapy reduced evening and morning serum hs-CRP and PTX3 levels in patients with moderate-to-severe OSA; however, the reduction in PTX3 levels in the morning was greater than that in the evening (morning -29.8 ± 16.7% vs. evening -12.6 ± 26.8%, P = 0.029). Improvement in the AHI score following CPAP therapy was strongly correlated with reduced morning PTX3 levels(r = 0.727, P < 0.001). Based on these results, morning PTX3 levels reflect OSA-related acute inflammation and are a useful marker for improvement in OSA following CPAP therapy.
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Successful treatment of a patient with purulent pericarditis by daily intrapericardial washouts.
Mai Terada, Hiroyuki Watanabe, Yusuke Kobukai, Takashi Koyama, Mamika Motokawa, Fumio Yamamoto, Hiroshi Ito
The Annals of thoracic surgery 98 ( 4 ) 1451 - 4 2014年10月 [査読有り]
研究論文（学術雑誌）
Purulent pericarditis in adults is rare, but once it develops, it carries a high mortality rate. Adequate pericardial drainage and proper antibiotic treatment are essential in the successful management of purulent effusions, for which percutaneous catheter drainage is the most commonly performed technique. We herein report the case of a 75-year-old woman with purulent pericarditis attributable to methicillin-resistant Staphylococcus aureus. Although percutaneous pericardial drainage by catheter was used, the drainage was insufficient because of hyperviscous effusion. We performed surgical subxiphoid pericardial drainage, and a piece of a purulent stone was found in the pericardial cavity with purulent effusion. Additionally, daily intrapericardial washouts with physiologic saline alone were used as adjunct therapy. Five weeks later, the patient had a decreasing inflammatory reaction and symptom relief. She was discharged with no complications such as constrictive pericarditis.
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Contralateral pulmonary embolism caused by pulmonary artery stump thrombosis after pneumonectomy.
Wakana Sato, Hiroyuki Watanabe, Teruki Sato, Kenji Iino, Kazuhiro Sato, Hiroshi Ito
The Annals of thoracic surgery 97 ( 5 ) 1797 - 8 2014年05月 [査読有り]
研究論文（学術雑誌）
A 73-year-old man with atrial fibrillation and previous left pneumonectomy was admitted with pleural effusion. Anticoagulant therapy was discontinued because of chest tube drainage. Six days later, the patient experienced chest discomfort. Echocardiography showed a pedunculated thrombus with swaying motion in the left pulmonary artery (PA) stump. Contrast-enhanced computed tomography of the chest revealed filling defects in not only the left PA stump but also the right PA, implying contralateral pulmonary embolism. Anticoagulants were resumed, and thrombolysis was successful 3 days later. Patients undergoing pneumonectomy in whom anticoagulant therapy is discontinued should be recognized as being at high risk for PA stump thrombosis and subsequent contralateral pulmonary embolism.
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Inhalation anesthesia is preferable for recording rat cardiac function using an electrocardiogram.
Manabu Murakami, Hidetoshi Niwa, Tetsuya Kushikata, Hiroyuki Watanabe, Kazuyoshi Hirota, Kyoichi Ono, Takayoshi Ohba
Biological & pharmaceutical bulletin 37 ( 5 ) 834 - 9 2014年05月 [査読有り]
研究論文（学術雑誌）
The effects of inhalation anesthesia (2% isoflurane, sevoflurane, or enflurane) and intraperitoneal anesthesia with pentobarbital (65 mg/kg) were compared in rats using an electrocardiogram (ECG) and determination of blood oxygen saturation (SPO2) levels. Following inhalation anesthesia, heart rate (HR) and SPO2 were acceptable while pentobarbital anesthesia decreased HR and SPO2 significantly. This indicates that inhalation anesthesia is more preferable than pentobarbital anesthesia when evaluating cardiovascular factors. Additionally, pentobarbital significantly increased HR variability (HRV), suggesting a regulatory effect of pentobarbital on the autonomic nervous system, and resulted in a decreased response of the baro-reflex system. Propranolol or atropine had limited effects on ECG recording following pentobarbital anesthesia. Taken together, these data suggest that inhalation anesthesia is suitable for conducting hemodynamic analyses in the rat.
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Immunochemical fecal occult blood tests predict dual antiplatelet therapy discontinuation after coronary stenting.
Ken Ikeda, Takashi Koyama, Masaru Ishida, Megumi Okawa, Yasunori Oguma, Yutaka Terata, Kenji Iino, Toshimitsu Kosaka, Hiroyuki Watanabe, Hiroshi Ito
Internal medicine (Tokyo, Japan) 53 ( 5 ) 375 - 81 2014年03月 [査読有り]
研究論文（学術雑誌）
OBJECTIVE: The discontinuation of dual antiplatelet therapy (DAPT) increases the risk of stent thrombosis after coronary stenting. Some patients must discontinue DAPT due to gastrointestinal (GI) tract disease; however, the type of examination that is most useful for detecting GI tract diseases has not been fully evaluated. The purpose of this study was to clarify whether the immunochemical fecal occult blood test (iFOBT) can be used to predict GI tract disease-related DAPT discontinuation following stent implantation in patients with coronary artery disease. METHODS: A total of 181 consecutive DAPT-naïve patients who underwent coronary stenting were divided into two groups according to the results of iFOBTs: a positive iFOBT group (n=32) and a negative iFOBT group (n=149). During the 12-month follow-up period, the DAPT discontinuation rate was lower in the negative iFOBT group than in the positive iFOBT group (3.4 vs. 18.8%, p=0.005). Kaplan-Meier event-free curves showed that the DAPT discontinuation rate in the negative iFOBT group was lower than that observed in the positive iFOBT group (log-rank test: p=0.001). Logistic and Cox regression analyses showed that a positive iFOBT result was the strongest predictor of the risk of DAPT discontinuation after coronary stenting. CONCLUSION: A positive iFOBT result is associated with DAPT discontinuation following coronary stenting.
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Apelin is a positive regulator of ACE2 in failing hearts.
Teruki Sato, Takashi Suzuki, Hiroyuki Watanabe, Ayumi Kadowaki, Akiyoshi Fukamizu, Peter P Liu, Akinori Kimura, Hiroshi Ito, Josef M Penninger, Yumiko Imai, Keiji Kuba
The Journal of clinical investigation 123 ( 12 ) 5203 - 11 2013年12月 [査読有り]
研究論文（学術雑誌）
Angiotensin converting enzyme 2 (ACE2) is a negative regulator of the renin-angiotensin system (RAS), catalyzing the conversion of Angiotensin II to Angiotensin 1-7. Apelin is a second catalytic substrate for ACE2 and functions as an inotropic and cardioprotective peptide. While an antagonistic relationship between the RAS and apelin has been proposed, such functional interplay remains elusive. Here we found that ACE2 was downregulated in apelin-deficient mice. Pharmacological or genetic inhibition of angiotensin II type 1 receptor (AT1R) rescued the impaired contractility and hypertrophy of apelin mutant mice, which was accompanied by restored ACE2 levels. Importantly, treatment with angiotensin 1-7 rescued hypertrophy and heart dysfunctions of apelin-knockout mice. Moreover, apelin, via activation of its receptor, APJ, increased ACE2 promoter activity in vitro and upregulated ACE2 expression in failing hearts in vivo. Apelin treatment also increased cardiac contractility and ACE2 levels in AT1R-deficient mice. These data demonstrate that ACE2 couples the RAS to the apelin system, adding a conceptual framework for the apelin-ACE2-angiotensin 1-7 axis as a therapeutic target for cardiovascular diseases.
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Remote ischemic pre-conditioning alleviates contrast-induced acute kidney injury in patients with moderate chronic kidney disease.
Gen Igarashi, Kenji Iino, Hiroyuki Watanabe, Hiroshi Ito
Circulation journal : official journal of the Japanese Circulation Society 77 ( 12 ) 3037 - 44 2013年12月 [査読有り]
研究論文（学術雑誌）
BACKGROUND: Although remote ischemic preconditioning (RIPC) is shown to preserve kidney function in patients at high risk of contrast-induced acute kidney injury (CI-AKI), the effect in patients at low-moderate risk remains unknown. The preventive effects of RIPC in patients not at high risk of CI-AKI were examined, and biomarkers with anticipated roles in renal protection via RIPC investigated. METHODS AND RESULTS: Sixty patients who had moderate chronic kidney disease and who underwent angiography were randomly assigned to the control (n=30) or RIPC (intermittent arm ischemia, n=30) group. The baseline characteristics in the 2 groups did not differ significantly. CI-AKI was evaluated by measuring urinary liver-type fatty acid-binding protein (L-FABP). Biomarkers were measured before and 24 and 48 h after angiography. Twenty-four hours after angiography, the percent change in urinary L-FABP level in the RIPC group was significantly smaller than in the control group (41.3±15.6 vs. 159±34.1%, P=0.003). L-FABP-based CI-AKI developed in 8 control patients (26.9%) vs. only 2 patients in the RIPC group (7.7%), suggesting that RIPC prevents CI-AKI. Factors contributing to CI-AKI were analyzed. Neither high-sensitivity C-reactive protein nor pentraxine-3 level differed significantly between the 2 groups, while the percent change in asymmetrical dimethy larginine (ADMA) level and blood derivatives of reactive oxidative metabolite levels were significantly smaller in the RIPC group. CONCLUSIONS: RIPC alleviates CI-AKI in patients at low-moderate risk. This effect might be mediated partly by decreasing oxidative stress and plasma ADMA level.
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Impaired renal function is a major determinant of left ventricular diastolic dysfunction: assessment by stress myocardial perfusion imaging.
Wakana Sato, Toshimitsu Kosaka, Takashi Koyama, Masaru Ishida, Kenji Iino, Hiroyuki Watanabe, Hiroshi Ito
Annals of nuclear medicine 27 ( 8 ) 729 - 36 2013年10月 [査読有り]
研究論文（学術雑誌）
OBJECTIVE: Relationships between myocardial scintigraphic parameters and renal function have not been fully determined. We investigated correlations between estimated glomerular filtration rate (eGFR) and left ventricular (LV) diastolic function using stress electrocardiographic (ECG)-gated myocardial single photon emission computed tomography (SPECT). METHODS: We enrolled 136 consecutive patients with suspected coronary artery disease (CAD) who were assessed using technetium-99m stress ECG-gated myocardial SPECT. We evaluated SPECT images using 17-segment defect scores graded on a 5-point scale, summed stress score, summed rest score and summed difference score (SDS). The parameters for assessing LV diastolic function were peak filling rate (PFR), 1/3 mean filling rate and time to peak filling. The CAD was defined as SDS ≥2. Chronic kidney disease (CKD) was defined as eGFR <60 mL/min/1.73 m(2). Patients were assigned to the following four groups (no CAD/no CKD: control group, n = 68; CAD/no CKD: CAD group, n = 24; no CAD/CKD: CKD group, n = 34; CAD/CKD: CAD + CKD group, n = 10). RESULTS: The PFR was significantly impaired after stress in the CKD and CAD + CKD groups compared with controls (p < 0.001 for both). Furthermore, PFR at rest positively correlated with eGFR (r = 0.29, p < 0.001) and inversely correlated with SDS (r = -0.18, p < 0.05). Multivariate stepwise regression analysis independently associated eGFR with PFR (β coefficient = 0.260, p = 0.002). CONCLUSIONS: Our data suggest that impaired renal function is a significant determinant of LV diastolic dysfunction in patients with suspected CAD.
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Rho-kinase in leukocytes. An emerging biomarker for heart failure.
Hiroyuki Watanabe, Kenji Iino, Hiroshi Ito
Circulation journal : official journal of the Japanese Circulation Society 77 ( 10 ) 2471 - 2 2013年10月 [査読有り]
研究論文（学術雑誌）
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Increased circulating CD3+/CD31+ T cells in patients with acute coronary syndrome.
Manabu Kakizaki, Kiyoshi Nobori, Hiroyuki Watanabe, Kenji Iino, Masaru Ishida, Hiroshi Ito
Heart and vessels 28 ( 5 ) 566 - 9 2013年09月 [査読有り]
研究論文（学術雑誌）
The number of circulating endothelial progenitor cells (EPCs) is considered to be a surrogate marker for coronary artery disease (CAD). Recent studies have identified a novel T-cell subset labeled with CD3(+)/CD31(+), which is necessary for EPC colony formation and constitutes the central cluster. However, the clinical relevance of the CD3(+)/CD31(+) T cells in CAD remains unclear. We sought to clarify whether circulating CD3(+)/CD31(+) T cells are increased in patients with acute coronary syndrome (ACS). Circulating CD3(+)/CD31(+) T cells were determined in 16 ACS patients undergoing emergency percutaneous coronary intervention (PCI) and in 16 control subjects with angiographically normal coronary arteries. Although no differences between the groups were found in baseline patient characteristics, the ratio of circulating CD3(+)/CD31(+) T cells before PCI was higher in ACS patients as compared with that in control subjects (51.8 % ± 7.8 % vs 31.8 % ± 9.6 %, respectively; P < 0.001). The increased ratio of CD3(+)/CD31(+) T cells in ACS patients was not altered 24 h after PCI, but became comparable with that in control subjects within 6 months after PCI. These results suggest that mobilization of CD3(+)/CD31(+) T cells occurs in ACS, but is no longer detectable at 6 months after PCI.
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Adaptive servo-ventilation therapy improves cardiac sympathetic nerve activity in patients with heart failure.
Takashi Koyama, Hiroyuki Watanabe, Yoshikazu Tamura, Yasunori Oguma, Toshimitsu Kosaka, Hiroshi Ito
European journal of heart failure 15 ( 8 ) 902 - 9 2013年08月 [査読有り]
研究論文（学術雑誌）
AIMS: This study investigated whether abnormal cardiac sympathetic nerve activity (SNA) is associated with the severity of central sleep apnoea (CSA) and whether adaptive servo-ventilation (ASV) therapy can improve cardiac SNA in heart failure (HF) patients with predominant CSA. METHODS AND RESULTS: Overnight polysomnography was conducted to diagnose CSA. Cardiac SNA was analysed by [123I]metaiodobenzylguanidine scintigraphy in 26 consecutive HF patients with predominant CSA. Of the 26 patients, 10 agreed to ASV therapy. Cardiac SNA was analysed 6 months after initiating ASV based on a non-randomized protocol. The apnoea-hypopnoea index and central apnoea index were significantly correlated with the washout rate (WR) and a delayed heart to mediastinal (H/M) ratio, suggesting that SNA is associated with abnormal breathing patterns. The WR, H/M ratio, plasma BNP level, and LVEF were significantly improved (WR, 40.0 ± 11.6% vs. 34.6 ± 11.4%, P = 0.046; H/M ratio, 1.5 ± 0.1 vs.1.8 ± 0.3, P = 0.013; ln BNP, 5.4 ± 1.0 vs. 4.6 ± 1.2, P = 0.007; and LVEF, 43.8 ± 10.4% vs. 47.0 ± 10.6%, P < 0.001) in the ASV group patients, but not in the non-ASV group patients. Multiple linear regression analyses showed that a decreased WR was strongly associated with an increased LVEF (coefficient = -0.454, P = 0.013). CONCLUSIONS: Abnormal cardiac SNA could be significantly correlated with the severity of CSA in HF patients. ASV therapy might improve cardiac function in these patients by partially mediating cardiac SNA regulation.
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Sildenafil prevents the up-regulation of transient receptor potential canonical channels in the development of cardiomyocyte hypertrophy.
Hironori Kiso, Takayoshi Ohba, Kenji Iino, Kazuhiro Sato, Yutaka Terata, Manabu Murakami, Kyoichi Ono, Hiroyuki Watanabe, Hiroshi Ito
Biochemical and biophysical research communications 436 ( 3 ) 514 - 8 2013年07月 [査読有り]
研究論文（学術雑誌）
BACKGROUND: Transient receptor potential canonical (TRPCs) channels are up-regulated in the development of cardiac hypertrophy. Sildenafil inhibits TRPC6 activation and expression, leading to the prevention of cardiac hypertrophy. However, the effects of sildenafil on the expression of other TRPCs remain unknown. We hypothesized that in addition to its effects of TRPC6, sildenafil blocks the up-regulation of other TRPC channels to suppress cardiomyocyte hypertrophy. METHODS AND RESULTS: In cultured neonatal rat cardiomyocytes, a 48 h treatment with 10nM endothelin (ET)-1 induced hypertrophic responses characterized by nuclear factor of activated T cells activation and enhancement of brain natriuretic peptide expression and cell surface area. Co-treatment with sildenafil (1 μM, 48 h) inhibited these ET-1-induced hypertrophic responses. Although ET-1 enhanced the gene expression of TRPCs, sildenafil inhibited the enhanced gene expression of TRPC1, C3 and C6. Moreover, co-treatment with sildenafil abolished the augmentation of SOCE in the hypertrophied cardiomyocytes. CONCLUSIONS: These results suggest that sildenafil inhibits cardiomyocyte hypertrophy by suppressing the up-regulation of TRPC expression.