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Masafumi Nakayama

Publications and source records attributed to Masafumi Nakayama.

At least 19 recordsLinked to original sources
PubMed2007

The effects of long-term smoking on endothelial nitric oxide synthase mRNA expression in human platelets as detected with real-time quantitative RT-PCR.

Endothelium-derived nitric oxide (NO) plays an important role in the prevention of platelet aggregation and adhesion to the vascular wall. Endothelial nitric oxide synthase (eNOS) and L-arginine/NO pathway are both present in human platelets. Platelet-derived NO inhibits excessive activation and aggregation of platelets. However, the expression level of the eNOS gene in human platelets has yet to be elucidated. The current study investigates the individual expression level of platelet eNOS mRNA using the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) detection method. eNOS mRNA expression was examined in platelets isolated from 50 subjects: 11 male smokers, 15 male nonsmokers, and 24 female non-smokers. After extraction of platelet total RNA, eNOS (target) and GAPDH (internal control) mRNA expression levels were quantitated using real-time RT-PCR. The expression levels of eNOS mRNA (relative copy numbers) were significantly lower in male smokers (59+/-17) than in male nonsmokers (195+/-71, P < .03), and higher in female nonsmokers (285+/-60) than in the male nonsmokers (195+/-71, P < .03). By multiple linear regression analysis, cigarette smoking (P = .008) and diabetes mellitus (P = .047) were found to be significantly negative predictors, and antioxidant (vitamin E) treatment (P = .01) was a significantly positive predictor of platelet eNOS mRNA expression. Age, other medications, and other risk factors for coronary artery disease were not significant. Using this method, eNOS mRNA abundance in human platelets was detected and quantitated in real-time. The intraplatelet eNOS mRNA expression levels were significantly decreased in cigarette smokers. Low platelet NO synthesis in smokers may result in the augmentation of platelet aggregation and thrombus formation, developing into acute coronary syndromes.

Adult↗
PubMed2006

A -786T>C polymorphism in the endothelial nitric oxide synthase gene reduces serum nitrite/nitrate levels from the heart due to an intracoronary injection of acetylcholine.

We identified a -786T>C polymorphism in the eNOS gene, and this polymorphism was strongly associated with coronary spasm. The present study aimed to elucidate whether the -786T>C polymorphism or acetylcholine (ACh)-induced coronary spasm affects serum nitrite/nitrate (NOx) levels. The study population comprised three groups: (i) 26 patients without coronary spasm in the left anterior descending coronary artery (LAD) with the T/T genotype (group A); (ii) 20 patients with coronary spasm in the LAD with the T/T genotype (group B); and (iii) 16 patients with coronary spasm in the LAD with the C/T genotype (group C). Paired blood samples were obtained from the coronary sinus (CS) and the aortic tract (Ao) before and after an intracoronary injection of ACh. Serum NOx and plasma lactate levels were measured. The delta NOx level was calculated as the serum concentration of NOx in the CS minus that in the Ao. We compared lactate extraction ratios (LERs) and delta NOx levels between the three groups. The LERs after the provocation test in groups A, B and C were 18.9+/-2.4%, -0.5+/-3.9% and -13.5+/-4.2%, respectively. The LER in group C was significantly lower than in group B. The delta NOx levels after the provocation test in groups A, B and C were 11.5+/-1.7 micromol/l, 10.4+/-3.5 micromol/l and -2.1+/-4.8 micromol/l, respectively. The delta NOx levels in group C were significantly lower (P<0.05). Although the NOx level was significantly increased after the provocation test in group A (P<0.05), the NOx level was significantly decreased after the provocation test in group C (P=0.001). In group B, the provocation test did not significantly change the delta NOx level. In conclusion, the -786T>C polymorphism reduces the NOx level from the heart due to an intracoronary injection of ACh, and thereby predisposes the patients to severe coronary spasm.

Acetylcholine↗
PubMed2006

[Coronary heart disease in patients with diabetes mellitus].

Diabetes mellitus is a well-recognized risk-factor for coronary artery disease. It is known that diabetic patients have a two-to fourfold increased risk of mortality or morbidity for cardiovascular diseases compared with the general population. Further, many diabetic patients with coronary heart disease have severe diseased coronary arteries: multi-vessel disease and/or severe stenosed vessel(s). In Japan, the prevalence of diabetic patients is rapidly increasing in these days. This article will review the evaluation for risk of coronary heart disease by measuring glucose level, the prognosis of diabetic patients, and the prevention of cardiovascular event in the patients with diabetes mellitus.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

Direct effects of aldosterone on cardiomyocytes in the presence of normal and elevated extracellular sodium.

It is now recognized that aldosterone is potentially cardiotoxic, although its local effects in the heart are not well understood. We examined the effects of aldosterone on cultured neonatal rat cardiomyocytes in the presence of normal and elevated extracellular Na+ ([Na+]o). We evaluated the intracellular volume of cardiomyocytes in the presence of normal (141 mEq/liter) and elevated (146 mEq/liter) [Na+]o by measuring cell size. Intracellular Na+ was measured using sodium-binding-benzofuran-isophthalate as a fluorescent sodium indicator, and cardiac hypertrophy was assessed using B-type natriuretic peptide transcription and (3)H-leucine incorporation. Cardiomyocytes shrank in the presence of 146 mEq/liter Na+ due to the increased extracellular osmolarity at early phase. Aldosterone (10(-7) mol/liter) mitigated the shrinkage by stimulating Na+ uptake by the cells. This effect of aldosterone was blocked by SM 20220, a Na+/H+ exchanger 1 (NHE1) inhibitor, but not by eplerenone, a mineralocorticoid receptor blocker. Seventy-two hours of exposure to aldosterone in the presence of 146 mEq/liter Na+ led to increases in cardiomyocyte size, 3H-leucine incorporation, and B-type natriuretic peptide and NHE1 transcription that were significantly greater than were seen in the presence of 141 mEq/liter Na+. All but the last were blocked by either eplerenone or SM 20220; the increase in NHE1 transcription was blocked only by eplerenone. Aldosterone exerts a beneficial effect via NHE1 to block cardiomyocyte shrinkage in the presence of elevated [Na+]o at early phase, but long-time exposure to aldosterone in the presence of elevated [Na+]o leads to cardiomyocyte hypertrophy via genomic effects mediated by the mineralocorticoid receptor.

Aldosterone↗
PubMed2005

TWEAK mediates anti-tumor effect of tumor-infiltrating macrophage.

TWEAK induces diverse cellular responses, including pro-inflammatory chemokine production, migration, proliferation, and cell death through the TWEAK receptor, Fn14. In the present study, we examined the effect of TWEAK or Fn14 expression in tumor cells on tumor outgrowth in vivo. Administration of neutralizing anti-TWEAK mAb significantly reduced the frequency of tumor rejection and shortened the survival of mice intraperitoneally inoculated with TWEAK-sensitive Fn14-expressing tumor cells. Moreover, anti-TWEAK mAb treatment promoted the subcutaneous growth of TWEAK-sensitive Fn14-expressing tumor cells, and this promotion was abolished by the inhibition of macrophage infiltration but not NK cell depletion. In contrast, administration of anti-TWEAK mAb had no apparent effect on the growth of TWEAK-resistant tumor cells, even if tumor cells expressed Fn14. On the other hand, TWEAK expression in tumor cells had no significant effect on subcutaneous tumor growth. These results indicate that TWEAK mediates anti-tumor effect of macrophages in vivo.

Animals↗
PubMed2005

Increase in the transcriptional activity of the endothelial nitric oxide synthase gene with fluvastatin: a relation with the -786T>C polymorphism.

HMG-CoA reductase inhibitors (statins) increase endothelial nitric oxide (NO) production, although the precise mechanism of this statin induced increase in NO production remains to be elucidated. We examined endothelial nitric oxide synthase (eNOS) mRNA levels, mRNA stability and the transcriptional activities of the eNOS gene in human umbilical vein endothelial cells treated with fluvastatin and simvastatin. We further examined whether the effects of these statins differ dependent upon the -786T>C polymorphism in the eNOS gene, and whether these statins affect gene expression of replication protein A1 (RPA1), which is known to reduce the transcriptional activity of the eNOS gene with the -786C allele. Utilizing the real-time reverse transcription-polymerase chain reaction, fluvastatin significantly increased eNOS mRNA levels and mRNA stability, and decreased RPA1 mRNA levels. Luciferase reporter gene assays revealed that fluvastatin significantly increased the transcriptional activity of the eNOS gene. The effect of fluvastatin was stronger in the -786C/C genotype than in the -786T/T genotype. Simvastatin increased eNOS mRNA levels and mRNA stability, but did not affect the transcriptional activity of the eNOS gene. Fluvastatin increased eNOS mRNA levels by enhancing both the transcriptional activity and mRNA stability. The effect of fluvastatin on the transcriptional activity was augmented in the -786C/C genotype, probably because of a decrease in RPA1 gene expression. Simvastatin increased eNOS mRNA levels only by enhancing mRNA stability. The present study suggests that fluvastatin increases endothelial NO activity and thus may be more beneficial to patients with the -786C allele.

Cell Line↗
PubMed2004

Possible association of heart failure status with synthetic balance between aldosterone and dehydroepiandrosterone in human heart.

BACKGROUND: Aldosterone is produced not only in the adrenal gland but also in the extra-adrenal tissues, including failing human heart. This study examined the production of dehydroepiandrosterone (DHEA) in human heart and elucidated the possible physiological significance. Method and Results- Using left ventricular tissues obtained at autopsy, reverse transcription-polymerase chain reaction followed by Southern blot analysis revealed the gene expressions of CYP17. By measuring plasma aldosterone and DHEA levels at the coronary sinuses and aortic roots during cardiac catheterization, we found that DHEA but not aldosterone was secreted from control subjects (P<0.0001 and P=0.74, respectively), whereas aldosterone but not DHEA was secreted from patients with heart failure (P=0.0017 and P=0.67, respectively). To examine the significance of DHEA, we measured myocyte cell sizes and the gene expression of B-type natriuretic peptide (BNP), using a neonatal rat cardiocyte culture system. We found that DHEA (10(-8) mol/L) significantly inhibited the increase in myocyte cell sizes and BNP mRNA levels upregulated by endothelin-1 (P=0.031 and P<0.0001, respectively). CONCLUSIONS: CYP17 gene expression and production of DHEA were demonstrated in human control heart. Also, we found that cardiac production of DHEA was suppressed in failing heart. We postulated that DHEA and/or its metabolites exert a cardioprotective action through antihypertrophic effects.

Adult↗
PubMed2004

Plasma level of B-type natriuretic peptide as a prognostic marker after acute myocardial infarction: a long-term follow-up analysis.

BACKGROUND: Circulating levels of B-type natriuretic peptide (BNP), a cardiac hormone, reflect the severity of cardiac dysfunction. Because the plasma BNP level changes dramatically during the period after the onset of acute myocardial infarction (AMI), identification of a suitable sampling time is problematic. There have been several reports indicating that the plasma BNP level obtained in the acute phase of AMI can be used as a prognostic marker. We examined whether the plasma BNP level measured 3 to 4 weeks after the onset of AMI represents a reliable prognostic marker for patients with AMI. METHODS AND RESULTS: We analyzed 145 consecutive patients with AMI. Plasma BNP levels were measured during the 3 to 4 weeks after onset of AMI. Of those patients, 23 experienced fatal cardiac events during this study. The mean follow-up period was 58.6 months. Log BNP, left ventricular end-diastolic pressure, and pulmonary vascular resistance were all significantly higher in the cardiac death group, and there were more men and more patients with a history of heart failure in the cardiac death group. A Cox proportional hazards model analysis showed that log BNP was an independent predictor of cardiac death. The survival rate was significantly higher in patients with log BNP <2.26 (180 pg/mL) than in those with log BNP > or =2.26. CONCLUSIONS: The plasma BNP level obtained 3 to 4 weeks after the onset of AMI can be used as an independent predictor of cardiac death in patients with AMI.

Adult↗
PubMed2004

Induction of RANTES by TWEAK/Fn14 interaction in human keratinocytes.

TNF-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor (TNF) family, is a multifunctional cytokine that regulate cellular proliferation, angiogenesis, inflammation, and apoptosis. In this study, we investigated the effect of TWEAK on human keratinocytes. Primary cultured normal human keratinocytes constitutively expressed a TWEAK receptor, fibroblast growth factor-inducible 14 (Fn14), and produced regulated on activation, normal T expressed and secreted (RANTES) upon TWEAK stimulation in a concentration-dependent manner. The TWEAK-induced RANTES production was abrogated by anti-Fn14 antibody, and synergistically augmented by simultaneous stimulation with transforming growth factor-beta. In addition, human keratinocytes differentiated in vitro with high Ca(2+)-containing medium showed enhanced production of RANTES upon TWEAK stimulation. Furthermore, TWEAK induced rapid phosphorylation of IkappaB-alpha in human keratinocytes. Collectively, TWEAK acts on human keratinocytes as an inducer of RANTES via Fn14. Because RANTES has been implicated in inflammation, TWEAK/Fn14 interaction in human keratinocytes may be involved in the pathophysiology of inflammatory skin disorders.

Apoptosis Regulatory Proteins↗
PubMed2003

Characterization of murine TWEAK and its receptor (Fn14) by monoclonal antibodies.

In the present study, we characterized murine TWEAK and its receptor (Fn14) by generating cDNA transfectants and specific monoclonal antibodies (mAbs). Recombinant murine TWEAK bound to murine Fn14-transfected L5178Y (mFn14/L5178Y) cells and induced cell death. Some anti-human Fn14 mAbs we previously generated strongly cross-reacted with murine Fn14 and induced cell death in mFn14/L5178Y cells. Murine TWEAK-transfected L5178Y cells expressed murine TWEAK on cell surface and secreted functional TWEAK, which were detected by a newly generated anti-murine TWEAK mAb (MTW-1). Although thioglycolate-elicited murine peritoneal macrophages did not express a detectable level of TWEAK on their surface, they secreted functional TWEAK that was cytotoxic against mFn14/L5178Y cells and neutralized by MTW-1. The anti-murine TWEAK and Fn14 mAbs will be useful for further investigating the physiological and pathological functions of TWEAK and Fn14.

Animals↗
PubMed2003

TWEAK induces NF-kappaB2 p100 processing and long lasting NF-kappaB activation.

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a member of the TNF superfamily that has been shown to induce angiogenesis, apoptosis in tumor cells, and NF-kappaB activation through binding to its receptor, fibroblast growth factor-inducible 14. We have identified TWEAK as an inducer of constitutive NF-kappaB activation by expression cloning, and we report here sequential regulation by TWEAK of two separate signaling cascades for NF-kappaB activation, the NF-kappaB essential modulator-dependent and -independent signaling pathways. Upon TWEAK stimulation, IkappaBalpha is rapidly phosphorylated, generating NF-kappaB DNA-binding complexes containing p50 and RelA in a manner dependent on the canonical IkappaB kinase complex. Unlike TNF-alpha, TWEAK stimulation results in prolonged NF-kappaB activation with a transition of the DNA-binding NF-kappaB components from RelA- to RelB-containing complexes by 8 h, and the latter remained active in binding at least until 24 h post-stimulation. This long lasting activation is accompanied by the proteasome-mediated processing of NF-kappaB2/p100, which does not depend on the NF-kappaB essential modulator but requires IkappaB kinase 1 and functional NF-kappaB-inducing kinase activity. Finally, we show that fibroblast growth factor-inducible 14 with a mutation at its TNF receptor-associated factor (TRAF)-binding site cannot activate NF-kappaB and that TWEAK fails to induce the p100 processing and IkappaBalpha phosphorylation in cells deficient for TRAF2 and TRAF5. Our results thus identify TWEAK as a novel physiological regulator of the non-canonical pathway for NF-kappaB activation.

Amino Acid Motifs↗
PubMed2003

Inhibitory effect of natriuretic peptides on aldosterone synthase gene expression in cultured neonatal rat cardiocytes.

BACKGROUND: Although previously thought to be synthesized solely in adrenal cortex, we have recently showed that aldosterone is also produced in and the expression of CYP11B2 mRNA was induced in the failing or hypertensive human ventricle. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones with wide biological effects, including inhibition of renin and aldosterone production. We hypothesized that natriuretic peptides reduce the expression of CYP11B2 mRNA in the heart. METHODS AND RESULTS: To test this hypothesis, we examined whether endogenous or exogenous natriuretic peptides reduce the expression of CYP11B2 mRNA using real-time reverse transcription-polymerase chain reaction. By using HS 142-1, a functional guanylyl cyclase-A type receptor antagonist, we showed that angiotensin II (AngII) pretreated with HS 142-1 increased CYP11B2 mRNA expression (1.62+/-0.12-fold, HS 142-1+AngII 10(-7) mol/L versus AngII 10(-7) mol/L alone, P<0.0001). The treatment with exogenous (10(-6) mol/L) ANP and BNP reduced CYP11B2 mRNA expression (ANP, P=0.0042; BNP, P=0.0012). CONCLUSIONS: We showed that endogenous and exogenous natriuretic peptides reduced CYP11B2 mRNA expression in cultured neonatal rat cardiocytes. This may inhibit the cardiac renin-angiotensin-aldosterone system by suppressing the gene expression of CYP11B2 and restraining cardiac hypertrophy and fibrosis.

Angiotensin II↗
PubMed2003

Fibroblast growth factor-inducible 14 mediates multiple pathways of TWEAK-induced cell death.

TWEAK, a TNF family member, is produced by IFN-gamma-stimulated monocytes and induces multiple pathways of cell death, including caspase-dependent apoptosis, cathepsin B-dependent necrosis, and endogenous TNF-alpha-mediated cell death, in a cell type-specific manner. However, the TWEAK receptor(s) that mediates these multiple death pathways remains to be identified. Recently, fibroblast growth factor-inducible 14 (Fn14) has been identified to be a TWEAK receptor, which was responsible for TWEAK-induced proliferation of endothelial cells and angiogenesis. Because Fn14 lacks the cytoplasmic death domain, it remains unclear whether Fn14 can also mediate the TWEAK-induced cell death. In this study, we demonstrated that TWEAK could induce apoptotic cell death in Fn14 transfectants. A pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, rather sensitized the Fn14 transfectants to TWEAK-induced cell death by necrosis via reactive oxygen intermediates and cathepsin B-dependent pathway. By using newly generated agonistic anti-Fn14 mAbs, we also observed that Fn14 is constitutively expressed on the cell surface of all TWEAK-sensitive tumor cell lines, and can transmit the multiple death signals. Moreover, an anti-Fn14 mAb that blocks TWEAK-Fn14 interaction could totally abrogate TWEAK binding and TWEAK-induced cell death in all TWEAK-sensitive tumor cell lines. These results revealed that the multiple pathways of TWEAK-induced cell death are solely mediated by Fn14.

Animals↗
PubMed2003

Synergistic interaction of T-786-->C polymorphism in the endothelial nitric oxide synthase gene and smoking for an enhanced risk for coronary spasm.

OBJECTIVE: We previously reported that a T-786-->C polymorphism in the 5'-flanking region of the endothelial nitric oxide synthase gene and smoking were independently associated with coronary spasm; however, the interaction between this polymorphism and smoking remains to be elucidated. METHODS: We analyzed 209 men and 238 women who were admitted consecutively at our institution; all subjects received an intracoronary injection of acetylcholine (ACh) while undergoing coronary angiography for evaluation of chest pain: all subjects had no significant coronary stenosis. We divided these subjects into four groups: non-smokers with T/T genotype (Control Group A); non-smokers with C/T or C/C genotype (Group B); smokers with T/T genotype (Group C); and smokers with C/T or C/C genotype (Group D). We further examined quantitative coronary angiographies of the left anterior descending coronary artery in a subset of 54 consecutive men and 53 consecutive women. RESULTS: The frequencies of coronary spasm in Group B (male: 61%, female: 78%), Group C (62%, 59%) and Group D (91%, 92%) were significantly higher than in Group A (30%, 38%). In the males, ACh-induced vasoconstriction was greatest in Group D, and the change was weakest in Group A. In the females, ACh-induced vasoconstrictions were significantly greater in Groups B, C and D than in Group A. The T-786-->C polymorphism and smoking combine to increase the risk of coronary spasm.

Acetylcholine↗
PubMed2002

Pro-inflammatory effect of TWEAK/Fn14 interaction on human umbilical vein endothelial cells.

TWEAK, a member of the TNF family, induces cell death in some tumor cell lines, but also induces proliferation of endothelial cells and angiogenesis. Recently, fibroblast growth factor-inducible 14 (Fn14) has been identified to be a TWEAK receptor, which may be responsible for the proliferation of endothelial cells and angiogenesis. In this study, we investigated the pro-inflammatory effect of TWEAK on human umbilical vein endothelial cells (HUVEC). We demonstrated that TWEAK could not only induce the proliferation and migration but also upregulate the cell surface expression of adhesion molecules such as ICAM-1 and E-selectin, and induce the secretion of chemokines such as IL-8 and MCP-1 in HUVEC. Moreover, by using an anti-Fn14 mAb that blocks the TWEAK/Fn14 interaction, we demonstrated that Fn14 was constitutively expressed on HUVEC and totally mediated the biological effects of TWEAK on HUVEC. These results indicated that TWEAK could induce pro-inflammatory reactions via Fn14 on HUVEC.

Animals↗
PubMed2002

B-type natriuretic peptide as a marker of the effects of enalapril in patients with heart failure.

BACKGROUND: A-Type and B-type natriuretic peptides are cardiac hormones whose circulating levels reflect the severity of heart failure. It is not known how plasma levels of these hormones respond to changes in cardiac function that occur as a result of treatment with angiotensin-converting enzyme (ACE) inhibitors. METHODS: Enalapril was administered at 5 mg/d for 3 months in 24 patients with chronic heart failure, and for the next 3 months at 15 mg/d in the high-dose group (n = 12) and 5 mg/d in the low-dose group (n = 12). We measured plasma levels of A-type or B-type natriuretic peptides, as well as conventional measures of cardiac function, such as the cardiothoracic ratio, left ventricular end-diastolic volume, and percent fractional shortening. RESULTS: Mean (+/- SD) plasma levels of both hormones decreased promptly after 2 weeks of therapy (A-type natriuretic peptide: 140 +/- 107 pg/mL to 81 +/- 68 pg/mL, P = 0.01; B-type natriuretic peptide: 305 +/- 278 pg/mL to 190 +/- 178 pg/mL, P = 0.01). These reductions were sustained throughout therapy. In contrast, the cardiothoracic ratio, left ventricular end-diastolic dimension, and percent fractional shortening had not changed significantly after 3 months of treatment, although improvements were seen after 6 months of treatment. After 6 months, plasma levels of both A-type and B-type natriuretic peptides were significantly lower in the high-dose group than in the low-dose group (A-type natriuretic peptide: 48 +/- 25 pg/mL vs. 57 +/- 27 pg/mL, P = 0.01; B-type natriuretic peptide: 78 +/- 58 pg/mL vs. 139 +/- 61 pg/mL, P = 0.005), whereas no significant differences were observed in the other measures of cardiac function. CONCLUSION: Plasma levels of A-type and B-type natriuretic peptides appear to be more sensitive markers of heart failure than conventional echocardiographic parameters and cardiothoracic ratios. Measurement of these hormones might be useful for monitoring the effects of treatment with ACE inhibitors.

Aged↗
PubMed2002

Effects of perindopril on aldosterone production in the failing human heart.

The present study was designed to examine whether the production of aldosterone from the heart is suppressed by angiotensin-converting enzyme (ACE) inhibition in patients with heart failure. Forty-one patients with left ventricular systolic dysfunction were randomly divided into either the perindopril group (n = 21, perindopril 4 mg/day) or the placebo group (n = 20). Plasma levels of aldosterone and ACE activity were measured in the anterior interventricular vein, coronary sinus, and aortic root during cardiac catheterization. The levels of aldosterone as well as ACE activity were significantly higher at the anterior interventricular vein and the coronary sinus than at the aortic root in the placebo group (aldosterone: 92.1 +/- 9.0 vs 70.6 +/- 8.3 pg/ml [p <0.001]; 90.3 +/- 9.2 vs 70.6 +/- 8.3 pg/ml [p <0.001], respectively; ACE activity: 13.6 +/- 0.8 vs 12.2 +/- 0.7 IU/L [p <0.001], 13.4 +/- 0.8 vs 12.2 +/- 0.7 IU/L [p <0.001], respectively). On the other hand, there were no differences in the levels of aldosterone or ACE activity between the anterior interventricular vein and aortic root or between the coronary sinus and aortic root (aldosterone: 68.1 +/- 8.4 vs 69.9 +/- 9.4 pg/ml [p = NS]; 67.3 +/- 8.9 vs 69.9 +/- 9.4 pg/ml [p = NS], respectively; ACE activity: 9.7 +/- 0.8 vs 9.9 +/- 0.8 IU/L [p = NS]; 9.8 +/- 0.8 vs 9.9 +/- 0.8 IU/L, respectively) in the perindopril group. The levels of aldosterone as well as ACE activity were significantly lower at the anterior interventricular vein and coronary sinus in the perindopril group than in the placebo group. The difference in the level of aldosterone between the anterior interventricular vein and aortic root (Delta aldosterone [anterior interventricular vein - aortic root]) had a significant positive correlation with that of ACE activity (Delta ACE [anterior interventricular vein - aortic root]) (r = 0.536, p <0.001), whereas ACE activity in the aortic root had no significant correlation with either the aldosterone levels in the aortic root or Delta aldosterone (anterior interventricular vein - aortic root). Perindopril suppressed cardiac aldosterone production by mainly suppressing cardiac ACE activity in patients with heart failure. Thus, aldosterone production is activated in the failing ventricle and is suppressed by perindopril mainly via the suppression of cardiac ACE activity in patients with heart failure.

Aldosterone↗