Biomedical subjects

Masato Ohnishi

Publications and source records attributed to Masato Ohnishi.

At least 19 recordsLinked to original sources

PubMed2006

Relationship between renal function and plasma brain natriuretic peptide in patients with heart failure.

OBJECTIVES: This study sought to evaluate the relationship between brain natriuretic peptide (BNP), renal function, and the severity of congestive heart failure (CHF). BACKGROUND: Both BNP and renal function are prognostic predictors in CHF patients. METHODS: We measured the plasma BNP level in the aortic root and coronary sinus in 366 consecutive patients with CHF. Estimated glomerular filtration rate (eGFR) by the Cockcroft-Gault equation was used as an indicator of renal function. RESULTS: By stepwise multivariate analyses, hemodynamic parameters such as left ventricular ejection fraction (LVEF) and left ventricular end-diastolic pressure (LVEDP) but not eGFR were independent predictors of a transcardiac increase (coronary sinus-aortic root) in BNP. Regarding the plasma level of BNP in the aortic root, not only LVEF (p < 0.0001) and LVEDP (p < 0.0001) but also eGFR (p < 0.0001) were independent predictors. Patients were divided into two groups, patients with an eGFR > or =60 ml/min (group 1, n = 229) and patients with an eGFR <60 ml/min (group 2, n = 137). There was no difference in LVEF, LVEDP, or the transcardiac gradient of BNP between the two groups, but the plasma level of BNP in the aortic root was approximately two-fold greater in group 2 than in the group 1. CONCLUSIONS: These findings suggest that decreased clearance from the kidney contributes to the elevated BNP in CHF patients with renal dysfunction, especially in patients with an eGFR <60 ml/min.

Aged↗

PubMed2004

Transcardiac increase in tumor necrosis factor-alpha and left ventricular end-diastolic volume in patients with dilated cardiomyopathy.

BACKGROUND: It remains unclear whether tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) are secreted from the failing heart and whether there is a relationship between the transcardiac gradients of these cytokines and left ventricular (LV) remodeling. AIMS: This study evaluated the relationship between transcardiac gradients of cytokines and LV volume and function in congestive heart failure patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS: We measured the plasma levels of TNF-alpha and IL-6 in the aortic root (Ao) and the coronary sinus (CS) in 60 patients with DCM. There was no difference in plasma IL-6 between the Ao and the CS. However, the plasma TNF-alpha level was significantly higher in the CS than that in the Ao. There was a significant correlation between the transcardiac gradient of plasma TNF-alpha and the LV end-diastolic volume index (LVEDVI) and LV ejection fraction. According to stepwise multivariate analyses, the transcardiac increase of TNF-alpha showed an independent and significantly positive relationship with a large LVEDVI. CONCLUSIONS: These results indicate that the elevated plasma TNF-alpha is partly derived from the failing heart in patients with DCM and that TNF-alpha plays a potential role in structural LV remodeling in patients with DCM.

Adult↗

PubMed2004

Long-term treatment with a phosphodiesterase type 5 inhibitor improves pulmonary hypertension secondary to heart failure through enhancing the natriuretic peptides-cGMP pathway.

In advanced heart failure (HF), the compensatory pulmonary vasodilation is attenuated due to the relative insufficiency of cGMP despite increased secretion of natriuretic peptides (NPs). Phosphodiesterase type 5 (PDE5) inhibitors prevent cGMP degradation, and thus may potentiate the effect of the NPs-cGMP pathway. We orally administered a specific PDE5 inhibitor, T-1032 (1 mg/kg; twice a day, n = 7) or placebo (n = 7) for 2 weeks in dogs with HF induced by rapid pacing (270 bpm, 3 weeks) and examined the plasma levels of atrial natriuretic peptide (ANP), cGMP, and hemodynamic parameters. We also examined the hemodynamic changes after injection of a specific NPs receptor antagonist, HS-142-1 (3 mg/kg), under treatment with T-1032. T-1032 significantly increased plasma cGMP levels compared with the vehicle group despite low plasma ANP levels associated with improvement in cardiopulmonary hemodynamics. HS-142-1 significantly decreased plasma cGMP levels in both groups, whereas it did not change all hemodynamic parameters in the vehicle group. In contrast, in the T-1032 group, HS-142-1 significantly increased pulmonary arterial pressure and pulmonary vascular resistance. These results indicated that long-term treatment with a PDE5 inhibitor improved pulmonary hypertension secondary to HF and the NPs-cGMP pathway contributed to this therapeutic effect.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2004

Endogenous bradykinin suppresses myocardial fibrosis through the cardiac-generated endothelin system under chronic angiotensin-converting enzyme inhibition in heart failure.

In congestive heart failure, angiotensin-converting enzyme inhibitors (ACEIs) may prevent cardiac fibrosis via interaction with both angiotensin II and endothelin-1, which enhance myocardial collagen synthesis. However, whether endogenous bradykinin with an ACEI modifies the cardiac collagen architecture, affecting the endothelin system, has not yet been fully elucidated. We evaluated the changes in circulating hormonal factors, myocardial fibrosis and cardiac gene expression closely linked with heart failure, using an orally active specific bradykinin type 2 receptor antagonist, FR173657 (0.3 mg/kg/day, n = 6), with an ACEI, enalapril (1 mg/kg/day), in dogs with tachycardia-induced congestive heart failure (270 p.p.m., 22 days) and compared the effects with enalapril alone (n = 6). Although there were no differences observed in blood pressure, plasma renin activity, aldosterone and endothelin-1 levels, combined FR173657 significantly increased the cardiac expression of preproendothelin- 1 mRNA (P < 0.05) and collagen type I and type III mRNA (P < 0.05), and cardiac collagen deposits (P < 0.05), and decreased eNOS gene expression (P < 0.05) in the left ventricle compared with the ACEI-treated group. Furthermore, there was a significant negative correlation between the expression of preproendothelin- 1 and eNOS mRNA levels (r = -0.708, P < 0.001). In conclusion, bradykinin may prevent cardiac fibrosis in part via suppression of the local endothelin system in the failing heart through the enhancement of nitric oxide production under chronic angiotensin-converting enzyme inhibition.

Aldosterone↗

PubMed2004

Contribution of vascular NAD(P)H oxidase to endothelial dysfunction in heart failure and the therapeutic effects of HMG-CoA reductase inhibitor.

BACKGROUND: The vascular NAD(P)H oxidase-derived superoxide anion (O(2)-) plays a crucial role in the pathological progression of hypertension and atherosclerosis, and HMG-CoA reductase inhibitors (statins) have vascular antioxidant effects. However, it is unclear whether the vascular NAD(P)H oxidase is involved in the endothelial dysfunction of congestive heart failure (CHF) and whether HMG-CoA reductase inhibitors (statins) exert their vasoprotective effects in CHF. The present study examined both the involvement of vascular NAD(P)H oxidase in endothelial dysfunction in dogs with tachycardia-induced CHF and the therapeutic effect of a statin (pitavastatin). METHODS AND RESULTS: Femoral blood flow (FBF) responses to acetylcholine was significantly impaired in the CHF group, but were improved by pitavastatin. Vascular O(2)- production, NAD(P)H oxidase activity and Nox4 and p47phox expression were significantly elevated in CHF compared with the normal group. The elevated O(2)-production in the CHF group was suppressed by the NAD(P)H oxidase inhibitor, apocynin, to the normal level. In contrast, neither the gene expression nor the activity of endothelial nitric oxide synthase (eNOS) differed significantly between the normal and CHF groups. However, pitavastatin significantly suppressed O(2)- production, NAD(P)H oxidase activity and Nox4 and p47phox expression and increased eNOS expression and activity compared with the CHF group. CONCLUSIONS: The activated vascular NAD(P)H oxidase contributes to endothelial dysfunction in CHF, which was partly improved by pitavastatin via its inhibition of NAD(P)H oxidase.

Acetylcholine↗

PubMed2003

Chymase inhibition prevents cardiac fibrosis and improves diastolic dysfunction in the progression of heart failure.

BACKGROUND: Angiotensin (Ang) II, which plays a crucial role in the cardiac remodeling process, is generated via angiotensin-converting enzyme (ACE); however, an alternative generation pathway, chymase, which is stored in the mast cells, also exists in the heart. Cardiac chymase is insensitive to ACE inhibitors (ACEIs), and heart chymase promotes interstitial fibrosis by affecting collagen metabolism via transforming growth factor-beta in vitro. Therefore, selective chymase blockade seems to be an important strategy in the prevention of cardiac remodeling METHODS AND RESULTS: We evaluated the effects of a specific chymase inhibitor, SUNC8257 (Chy I; 10 mg/kg twice a day; n=7), on changes in cardiac structures, Ang II levels, and gene expressions, which are characterized as molecular markers for fibrosis, in dogs with tachycardia induced heart failure (HF). In HF, the number of chymase enzyme-positive mast cells increased in the left ventricle (LV) compared with the normal group; however, Chy I significantly decreased the mast cell density and cardiac Ang II levels. Despite no significant differences in LV systolic function compared with the vehicle group, Chy I decreased LV end-diastolic pressure and shortened the prolongation of tau. Chy I suppressed collagen-type I and III and transforming growth factor-beta mRNA levels and decreased fibrosis in the LV compared with the vehicle. CONCLUSIONS: The chymase pathway may be critical for cardiac diastolic dysfunction accompanied with fibrosis. Chronic chymase inhibition may therefore become an important strategy in the prevention of cardiac remodeling in HF.

Angiotensin II↗

PubMed2003

Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents post-infarct left ventricular remodeling associated with suppression of a marker of myocardial collagen synthesis in patients with first anterior acute myocardial infarction.

BACKGROUND: Aldosterone (ALD) has been shown to stimulate cardiac collagen synthesis and fibroblast proliferation via activation of local mineralocorticoid receptors. In patients with acute myocardial infarction, we demonstrated that ALD was extracted through the infarct heart and extracting ALD-stimulated post-infarct left ventricular (LV) remodeling. METHODS AND RESULTS: To evaluate the effect of mineralocorticoid receptor antagonist (MRA) spironolactone on post-infarct LV remodeling, 134 patients with first anterior acute myocardial infarction were randomly divided into the MRA (n=65) or non-MRA (n=69) groups after revascularization. All patients were administered angiotensin-converting enzyme (ACE) inhibitor and study drug just after revascularization. Left ventriculography with contrast medium was performed at the acute stage and after 1 month to evaluate LV remodeling. ALD was measured at aortic root and coronary sinus. There was no difference in the baseline characteristics including infarct size and LV performance between the two groups. However, LV ejection fraction was significantly improved in the MRA group compared with that in the non-MRA group (46.0+/-0.6% to 53.2+/-0.8% versus 46.5+/-0.8% to 51.0+/-0.8%, Pinteraction=0.012). LV end-diastolic volume index was significantly suppressed in the MRA group compared with that in non-MRA group (86.5+/-1.0 to 90.6+/-2.4 versus 87.5+/-1.3 to 106.8+/-3.5 mL/m2, Pinteraction=0.002). Transcardiac extraction of ALD through the heart was significantly suppressed in the MRA group (Pinteraction=0.001), and plasma procollagen type III aminoterminal peptide level, a biochemical marker of fibrosis, was significant lower in the MRA group compared with the non-MRA group (Pinteraction=0.002). CONCLUSIONS: These findings indicate that MRA combined with ACE inhibitor can prevent post-infarct LV remodeling better than ACE inhibitor alone in association with the suppression of a marker of collagen synthesis.

Adrenergic beta-Antagonists↗

PubMed2003

Effect of an angiotensin II type 1 receptor blocker, valsartan, on neurohumoral factors in patients with hypertension: comparison with a long-acting calcium channel antagonist, amlodipine.

This study compared the effects of amlodipine and valsartan on the sympathetic nervous system, the renin-angiotensin-aldosterone system, and brain natriuretic peptide, which are considered important parameters of the long-term prognosis. Seventy-three elderly patients, who had received antihypertensive treatment for more than 6 months with amlodipine, participated in this study. They were randomized to the V group (n = 36) and switched to valsartan from amlodipine, or to the A group (n = 37), which continued treatment with amlodipine. The dose of valsartan was set as that which controlled the blood pressure to the same extent as before switching. Blood samples were measured before and after 6 months of therapy. Data were analyzed by two-way analysis of variance with the Newman-Keuls test. In the V group, norepinephrine (from 597.0 +/- 52.9 to 475 +/- 43.8 pg/ml, p < 0.05) and aldosterone (from 74.5 +/- 7.0 to 53.9 +/- 5.3 pg/ml, p < 0.001) were decreased significantly after 6 months, although norepinephrine and aldosterone levels were unchanged in the A group. However, brain natriuretic peptide did not show a difference between the two groups. These findings suggested that valsartan is probably superior to amlodipine with respect to less activation of the sympathetic nervous system and preventing upregulation of the renin-angiotensin-aldosterone system.

Aged↗

PubMed2003

Transcardiac gradient of aldosterone before and after spironolactone in patients with congestive heart failure.

To evaluate the transcardiac extraction of aldosterone before and after spironolactone administration to patients with congestive heart failure, we measured the plasma aldosterone in the aortic root and the coronary sinus in eight congestive heart failure patients with dilated cardiomyopathy. The plasma aldosterone level was significantly lower in the coronary sinus than in the aortic root before spironolactone administration (87.5 +/- 16 versus 62.2 +/- 11 pg/ml, p = 0.01). After chronic treatment with spironolactone, there was no significant difference in the aldosterone level between the aortic root and the coronary sinus (151 +/- 49 versus 148 +/- 48 pg/ml), and the transcardiac gradient of aldosterone (aortic root to coronary sinus) was significantly decreased (25.3 +/- 7.3 versus 3.1 +/- 4.5 pg/ml, p = 0.046). These results indicate that plasma aldosterone is extracted through the heart in congestive heart failure patients with dilated cardiomyopathy, and that spironolactone inhibits the transcardiac extraction of aldosterone in congestive heart failure patients. This suggests that spironolactone blocks the effects of aldosterone on the failing heart in congestive heart failure patients with dilated cardiomyopathy.

Adult↗

PubMed2003

Effects of long-acting calcium channel antagonists on neurohumoral factors: comparison of nifedipine coat-core with amlodipine.

Calcium channel antagonists can induce sympathetic hyperactivity, leading to a poor prognosis for hypertensive patients. Nifedipine formulations that allow once-daily administration are now available for use in clinical practice. To compare the effects of nifedipine with those of amlodipine, we studied 36 essential hypertensive patients. Those who had been administered nifedipine sustained-release were treated with amlodipine in place of nifedipine sustained-release, and those who had been administered amlodipine were treated with nifedipine coat-core in place of amlodipine. Substitution of nifedipine sustained-release by amlodipine had no significant effect on hypertensive symptoms. However, the plasma levels of norepinephrine, renin, and aldosterone were significantly lower (p < 0.001-0.05) in patients taking amlodipine in place of nifedipine sustained-release. Substitution of amlodipine by nifedipine coat-core again had no significant effect on hypertensive symptoms. However, the plasma levels of norepinephrine, renin, and aldosterone did not change significantly after the substitution. These findings indicate that, at the effective anti-hypertensive concentrations of nifedipine coat-core and amlodipine, nifedipine coat-core may not increase sympathetic nerve activity as is observed with amlodipine. The results also suggest that the duration of action of nifedipine formulations is an important determinant for nifedipine-induced hyperactivity in the reflex sympathetic nerve and the renin-angiotensin systems.

Aged↗

PubMed2003

Development of nursing care support system using PDA with wireless and barcode reader.

In this study, we developed nursing care support system using Personal Digital Assistants (PDA) with wireless and barcode reader. Our goals were to minimize the cost of deployment, to maximize the ease of operation, and to adapt to existing features and tasks of nursing care. The success of achieving these objectives was evaluated from the case study results involving system training session and trial of the system at a university hospital.

Computers, Handheld↗

PubMed2002

Plasma oxidized low-density lipoprotein as a prognostic predictor in patients with chronic congestive heart failure.

OBJECTIVES: The aim of this study was to evaluate the relationship between plasma oxidized low-density lipoprotein (oxLDL), a marker of oxidative stress, and the prognosis of patients with chronic congestive heart failure (CHF). BACKGROUND: Oxidative stress appears to play a role in the pathophysiology of CHF. We have recently reported the usefulness of plasma oxLDL as a marker of oxidative stress in CHF patients with dilated cardiomyopathy. METHODS: We measured the plasma level of oxLDL by sandwich enzyme-linked immunosorbent assay using a specific monoclonal antibody against oxLDL in 18 age-matched normal subjects and in 84 patients with chronic CHF (New York Heart Association functional class II to IV) and monitored them prospectively for a mean follow-up period of 780 days. RESULTS: Plasma oxLDL level was significantly higher in severe CHF patients than in control subjects and mild CHF patients. A significant negative correlation existed between the plasma level of oxLDL and left ventricular ejection fraction (LVEF) and a significant positive correlation between the plasma level of oxLDL and plasma norepinephrine level. Twenty-six patients had cardiac events; 14 had cardiac death and 12 were hospitalized for heart failure or other cardiovascular events. Among 10 variables including LVEF and neurohumoral factors, only high plasma levels of brain natriuretic peptide and oxLDL were shown to be independent predictors of mortality. CONCLUSIONS: These results indicate that the plasma level of oxLDL is a useful predictor of mortality in patients with CHF, suggesting that oxidative stress plays an important role in the pathophysiology of CHF.

Adolescent↗

PubMed2002

Endothelin stimulates an endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine, in experimental heart failure.

Congestive heart failure (CHF) is characterized by increased peripheral vascular resistance. Endothelin-1 (ET-1), a potent endothelium-derived vasoconstrictor, is present at increased concentrations in the plasma and contributes to the regulation of vascular tone in CHF. An endothelium-derived relaxing factor, nitric oxide (NO), also regulates vascular tone, but endothelium-dependent NO-mediated vasodilation is blunted in CHF. An endogenous NO synthase inhibitor, asymmetric dimethylarginine (ADMA), which inhibits NO production and endothelium-dependent relaxation, is present at increased levels in the plasma and plays a role in impaired endothelial function in CHF. However, at present, the relationship between ET-1 and impaired vascular relaxation in CHF is not well known. We hypothesized that ET-1 inhibits NO-mediated vasodilation via increased ADMA production in CHF, and that an endothelin receptor antagonist can prevent this increase in plasma ADMA levels. In the present study, we first examined whether circulating ADMA levels were increased in a dog model of CHF induced by 3 weeks of rapid ventricular pacing (n=5; 270 beats/min) compared with normal dogs (n=5). After 3 weeks of pacing, cardiac output had decreased significantly (1.56+/-0.16 compared with 2.93+/-0.25 litres/min; P<0.01) and systemic vascular resistance had increased (4653+/-374 compared with 3227+/-396 dyn.s.cm(-5); P<0.01) in dogs with CHF compared with normal dogs. Plasma levels of both ET-1 (4.95+/-0.83 compared with 2.12+/-0.39 pg/ml; P<0.05) and ADMA (3.27+/-0.49 compared with 1.91+/-0.25 nmol/ml; P<0.05) were significantly increased in CHF dogs. A significant positive correlation was observed between plasma ET-1 and ADMA levels (r=0.72, P<0.05). Secondly, we chronically administered an ET(A) receptor antagonist, TA-0201 (0.3 mg/kg; n=5), to paced CHF dogs. Drug administration started on day 8 of pacing and continued throughout the experiment. TA-0201 significantly increased cardiac output (2.58+/-0.24 litres/min; P<0.01) and suppressed the increases in plasma ADMA levels and systemic vascular resistance (2.36+/-0.30 nmol/ml and 2423+/-188 dyn.s.cm(-5) respectively; P<0.05 for each) compared with CHF dogs without TA-0201 treatment. In conclusion, ET-1 contributes to the regulation of vascular tone due, in part, to increased levels of an endogenous NO synthase inhibitor in CHF, and an ET(A) receptor antagonist can prevent the inhibition of NO production and the increased peripheral vascular resistance observed in CHF.

Animals↗

PubMed2002

Chronic effects of an endothelin-converting enzyme inhibitor on cardiorenal and hormonal function in heart failure.

Endothelin (ET)-converting enzyme (ECE) is a rate-limiting step in ET-1 generation, and its expression and activity are increased significantly with the development of congestive heart failure (CHF). The selective enzymic inhibition of ET-1 formation thus seems to be a very important target in the prevention of CHF. We evaluated the chronic effects of a specific ECE inhibitor, FR901533 (0.3 mg x kg(-1) x h(-1), n=5) on cardiac, hormonal, and body fluid balance in dogs with CHF induced by rapid right ventricular pacing (270 beats/min, 22 days). Vehicle dogs were given placebo (n=5). Despite no significant difference in blood pressure, FR901533 decreased pulmonary capillary wedge pressure and increased cardiac output compared with the vehicle. FR901533 prevented the reduction of urine flow rate and urinary sodium excretion in association with an increase in the glomerular filtration rate and renal plasma flow compared with the vehicle. FR901533 also suppressed significantly the elevation of plasma atrial natriuretic peptide and aldosterone levels which is an established prognostic factor in CHF. These results indicate that the role of ECE in CHF is important and that chronic ECE inhibition could possess therapeutic potential in the treatment of CHF not only on haemodynamics but also in the prevention of fluid retention.

Aldosterone↗

PubMed2002

Chronic administration of phosphodiesterase type 5 inhibitor suppresses renal production of endothelin-1 in dogs with congestive heart failure.

Endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) play important roles in the regulation of body fluid balance in congestive heart failure (CHF). Renal production of ET-1 increases in CHF and it is a significant independent predictor of sodium excretion. ANP inhibits the ET system through cGMP, a second messenger of ANP. However, in severe CHF, plasma cGMP levels reached a plateau despite the activation of ANP secretion. Thus, ANP does not seem to sufficiently oppose exaggerated ET-1 actions in severe CHF, partially due to the accelerated degradation of cGMP, through phosphodiesterase type 5 (PDE5). We examined the chronic effects of a PDE5 inhibitor, T-1032 (1 mg/kg per day, n=5), on renal function and renal production of ET-1 in dogs with CHF induced by rapid ventricular pacing (270 beats/min). Vehicle dogs were given a placebo (n=5) and normal dogs (n=5) served as normal controls without pacing. In this experimentally produced CHF, plasma levels of ET-1, ANP and cGMP were elevated and renal production of cGMP was increased compared with the normal group, associated with increases in renal expression of preproET-1 mRNA and the number of ET-1-positive cells in glomeruli. In the T-1032 group, systemic and renal production of cGMP were further increased compared with the vehicle group despite no significant difference in plasma ANP levels between the two groups. Subsequently, the agent significantly improved urine flow rate, sodium excretion rate and glomerular filtration rate (GFR) associated with reductions in renal expression of preproET-1 mRNA and the number of ET-1-positive cells compared with the vehicle group. Moreover, there was a significant negative correlation between the number of ET-1-positive cells and GFR (r=-0.802 and P<0.001 respectively). Our results indicate that chronic PDE5 inhibition ameliorates the antagonistic relationship between renal ANP and ET-1 through the cGMP pathway, subsequently preventing renal dysfunction during the progression of CHF.

Animals↗

PubMed2002

Bradykinin improves left ventricular diastolic function under long-term angiotensin-converting enzyme inhibition in heart failure.

Both systolic and diastolic cardiac dysfunction coexist in various degrees in the majority of patients with heart failure. Although ACE inhibitors are useful in the treatment of heart failure, the roles of bradykinin in the systolic and diastolic properties of left ventricular function under long-term treatment of ACE inhibitor have not been fully elucidated. We therefore evaluated the changes in left ventricular function, histomorphometry, and the expression of several failing heart related genes, by use of an orally active specific bradykinin type 2 receptor antagonist, FR173657 (0.3 mg/kg per day), with an ACE inhibitor, enalapril (1 mg/kg per day), in dogs with tachycardia-induced heart failure (270 ppm, 22 days) and compared the effects to enalapril alone. Although there were no differences observed in blood pressure, left ventricular dimension, and percentage of fractional shortening, FR173657 significantly increased left ventricular filling pressure (P<0.01), prolonged the time constant of relaxation (P<0.05), and suppressed the expression of endothelial NO synthase and sarcoplasmic reticulum Ca(2+)-ATPase mRNA (P<0.05). FR173657 also upregulated collagen type I and III mRNA (P<0.05) and increased the total amount of cardiac collagen deposits (P<0.05) in left ventricle compared with that in the enalapril-treated group. In conclusion, endogenous bradykinin contributes to the cardioprotective effect of ACE inhibitor, improving left ventricular diastolic dysfunction rather than systolic dysfunction, via modification of NO release and Ca(2+) handling and suppression of collagen accumulation.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2002

Relationship between interleukin-6 production in the lungs and pulmonary vascular resistance in patients with congestive heart failure.

STUDY OBJECTIVES: We evaluated whether interleukin (IL)-6 is produced in the pulmonary circulation and investigated the relationship between IL-6 spillover in the lung and pulmonary vascular resistance (PVR) in patients with congestive heart failure (CHF). PATIENTS AND INTERVENTIONS: Blood samples were obtained from the main pulmonary artery and pulmonary capillary wedge region in 50 patients with symptomatic left ventricular dysfunction, who had undergone cardiac catheterization, and 9 age-matched control subjects. Plasma IL-6, tumor necrosis factor-alpha, norepinephrine (NE), endothelin-1, atrial and brain natriuretic peptide, and cyclic guanosine monophosphate (cGMP) levels were determined. MEASUREMENTS AND RESULTS: Plasma IL-6 concentrations were significantly higher in the pulmonary capillary wedge region than in the main pulmonary artery in both control subjects and patients with CHF. IL-6 production in the lung increased markedly in patients with severe CHF compared with control subjects and patients with mild CHF. Among hemodynamic variables, neurohumoral factors, and medications, plasma NE levels (p < 0.0001) showed an independent and significant positive relationship with IL-6 production in the lung, and treatment with beta-blockers (p = 0.004) showed an independent and significant negative relationship with IL-6 production in the lung. There was a significant positive correlation between IL-6 production in the lung and both PVR (r = 0.43; p = 0.001) and cGMP production in the lung (r = 0.498; p < 0.0001). CONCLUSION: IL-6 production in the pulmonary circulation increases with the severity of CHF and is mainly associated with the activation of the sympathetic nervous system. The local production of IL-6 in the lung may modify PVR in patients with CHF.

Adult↗

PubMed2002

[Comparative effects of losartan and amlodipine on activities of sympathetic nerve, renin-angiotensin-aldosterone system and brain natriuretic peptide in the elderly hypertensive patients].

This study investigated the comparative effects of losartan and amlodipine on the activation of the sympathetic nervous system, renin-angiotensin-aldosterone system (R-A-A system) and brain natriuretic peptide (BNP) in patients with essential hypertension. Twenty-four elderly patients who had received more than 12 months of antihypertensive treatment with amlodipine participated in this study. The treatment regimen of 5 mg/day amlodipine was changed to 50 mg/day losartan. Plasma catecholamines (norepinephrine, epinephrine and dopamine), active renin, aldosterone and BNP concentration were measured before and after an average of 5 months of losartan treatment. After losartan treatment, blood pressures were not changed, suggesting the comparable effect of 50 mg losartan and 5 mg amlodipine on elevated blood pressure. Losartan significantly reduced norepinephrine (799 +/- 277 pg/mL vs. 692 +/- 268 pg/mL, p < 0.05) and aldosterone concentration (81.2 +/- 35.3 pg/mL vs. 55.2 +/- 17.7 pg/mL, p < 0.01), whereas there were not any changes in BNP concentrations. These findings suggested that losartan might be superior to amlodipine in prevention of chronic or intermittent sympathetic hyperactivity and enhanced R-A-A system.

Aged↗