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Biomedical subjects

T Nishikimi

Publications and source records attributed to T Nishikimi.

At least 55 records · Page 3Linked to original sources
PubMed1999

Effects of long-term treatment with pimobendan on neurohumoral factors in patients with non-ischemic chronic moderate heart failure.

To evaluate the effects of the addition of pimobendan to an optimal basic regimen on plasma levels of neurohumoral factors in patients with non-ischemic, moderate heart failure during 2-year follow-up. This prospective, observational study involved 16 patients with non-ischemic, moderate heart failure [New York Heart Association (NYHA) functional class IIM-III] receiving an optimal basic regimen of digitalis, diuretics and angiotensin-converting enzyme inhibitor. Eight patients (Group P) were also administered pimobendan at a dose of 2.5 or 5 mg daily, while the other 8 served as controls (Group C). After 3 months of pimobendan administration, the plasma levels of norepinephrine and atrial natriuretic peptide and brain natriuretic peptide decreased and left ventricular ejection fraction improved. After 1 year, the cardiac symptoms, assessed using the Specific Activity Scale as well as the NYHA functional class, improved and the left ventricular end-diastolic diameter decreased. These improvements in Group P were maintained for 2 years. However, in Group C, the cardiac symptoms and the neurohumoral factor levels remained unchanged or deteriorated during this study, and one patient died of heart failure. Long-term combination therapy with the optimal basic regimen and pimobendan has potentially beneficial effects on neurohumoral factor levels and cardiac symptoms in patients with non-ischemic, chronic moderate heart failure.

Adult↗
PubMed1999

Increased plasma levels of adrenomedullin in patients with pulmonary hypertension.

Adrenomedullin, a potent hypotensive peptide, reduces blood pressure and pulmonary vascular resistance, and increases pulmonary blood flow. The mRNA for adrenomedullin and its receptor is highly expressed in the lung, suggesting a regulatory role for adrenomedullin in the pulmonary circulation. To investigate the clinical significance of adrenomedullin in patients with pulmonary hypertension, we studied the relationship between plasma levels of adrenomedullin and pulmonary haemodynamics. Venous, arterial and pulmonary arterial blood samples were obtained during cardiac catheterization and plasma levels of adrenomedullin were measured by specific radioimmunoassay in 33 consecutive patients with severe pulmonary hypertension (12 cases of primary pulmonary hypertension, 21 with chronic thromboembolic pulmonary hypertension; age 49+/-16 years, mean pulmonary arterial pressure 50+/-15mmHg). In addition, plasma levels of adrenomedullin were measured before and after acute nitric oxide inhalation. The changes in plasma adrenomedullin during the follow-up period of 10.3+/-4.3 months were also evaluated (n=5). Sixty-two healthy subjects served as the control group. Adrenomedullin was measured in an antecubital vein in the controls. Plasma levels of adrenomedullin were significantly higher in the patients with pulmonary hypertension than in the control subjects (10.1+/-8.7 versus 4.9+/-1.1pmol/l, P<0.01). Plasma levels of adrenomedullin, expressed as their natural logarithm, were significantly correlated with mean right atrial pressure (r=0.71, P<0.01), stroke volume (r=-0.63, P<0.01), total pulmonary resistance (r=0.60, P<0.01), mean pulmonary arterial pressure (r=0.37, P<0.05), and the natural logarithm of plasma atrial natriuretic peptide (r=0. 63, P<0.01). Plasma levels of adrenomedullin did not change significantly after nitric oxide inhalation, but significantly increased in association with the elevation of the total pulmonary resistance during the long-term follow-up period. These results suggest that plasma levels of adrenomedullin increase in proportion to the extent of pulmonary hypertension.

Administration, Inhalation↗
PubMed1999

Sustained elevation of plasma brain natriuretic peptide levels associated with progressive ventricular remodelling after acute myocardial infarction.

Previous studies have shown that levels of plasma brain natriuretic peptide (BNP) increase in an early phase of acute myocardial infarction. However, the relations between plasma BNP levels and left ventricular remodelling, which occurs long after acute myocardial infarction, are not fully understood. Venous plasma BNP levels were measured 2, 7, 14, 30, 90 and 180 days after the onset of acute myocardial infarction in 21 patients. Left ventricular end-diastolic volume index (EDVI, ml/m2) in acute (5 days) and chronic (6 months) phases were assessed by electron-beam computed tomography using Simpson's method. The remodelling group (n=9) was defined by an increase in EDVI >/=5 ml/m2 relative to the baseline value. Plasma BNP levels on days 2, 7, 14, 30 and 90 were significantly higher in the remodelling group than in the non-remodelling group (n=12, P<0.05). Sustained elevation of plasma BNP levels was noted from day 2 (61+/-12 pmol/l) to day 90 (55+/-12 pmol/l) and significantly decreased on day 180 (24+/-3 pmol/l) in the remodelling group. In contrast, plasma BNP levels significantly decreased from day 2 (25+/-4 pmol/l) to day 90 (9+/-1 pmol/l) and reached a steady level thereafter in the non-remodelling group. Plasma BNP levels on day 7 correlated positively with an increase in EDVI (r=0.70, P<0.001) from the acute to chronic phase. More importantly, the sustained elevation of plasma BNP (percentage decrease smaller than 25%) from day 30 to day 90 identified patients in the remodelling group with a sensitivity of 100% and a specificity of 83%. In conclusion, not only the high levels of plasma BNP in an acute phase, but also the sustained elevation of plasma BNP in a chronic phase, may be associated with progressive ventricular remodelling occurring long after acute myocardial infarction.

Adult↗
PubMed1998

Diagnostic value of plasma levels of brain natriuretic peptide in arrhythmogenic right ventricular dysplasia.

BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by local or diffuse wall motion abnormalities in the right ventricle (RV), associated with recurrent ventricular tachycardia (VT) of RV origin. Brain natriuretic peptide (BNP) was first isolated from a porcine brain extract. In humans, BNP is expressed predominantly in the ventricles of failing hearts, and its expression has been observed primarily in myocytes in the interstitial fibrous area in dilated cardiomyopathy. We hypothesized that BNP is increasingly secreted from the residual myocytes within the atrophic tissue in patients with ARVD. METHODS AND RESULTS: Plasma BNP levels were measured in 17 patients with ARVD, 12 patients with idiopathic RV outflow tract tachycardia (RVOT), and 120 control subjects. We performed cardiac catheterization, RV endomyocardial biopsy, electron- beam CT, and biventricular endomyocardial mapping in the ARVD patients. There was a significant increase in plasma BNP levels in the ARVD patients compared with the RVOT patients and control subjects (61.4+/-59.6 pg/mL versus 8.3+/-5. 5 pg/mL and 9.3+/-5.8 pg/mL; P<0.0001, respectively). The plasma BNP levels had no correlation with any of the hemodynamic data, but they had a significant correlation with the RV ejection fraction (r=-0. 588, P=0.025) and with the fractionated-area scores (r=0.705, P=0. 005). Light microscopic immunohistochemistry showed strong BNP immunoreactivity in residual myocytes with fibrofatty replacement. CONCLUSIONS: These results suggest that plasma BNP levels were not increased in RVOT patients but were increased in ARVD patients, and that the increased BNP levels indicate the severity of both the RV dysfunction and the arrhythmogenic substrate.

Adolescent↗
PubMed1998

Chronic infusion of adrenomedullin reduces pulmonary hypertension and lessens right ventricular hypertrophy in rats administered monocrotaline.

A novel vasorelaxant peptide, adrenomedullin, its messenger ribonucleic acid (mRNA), and the mRNA for its receptor are highly expressed in the lung, suggesting that adrenomedullin may play a role in the regulation of the pulmonary circulation. We investigated whether the chronic infusion of rat adrenomedullin would affect pulmonary hypertension and right ventricular hypertrophy produced by the administration of monocrotaline. Four-week-old male Wistar rats received a single subcutaneous injection of 60 mg/kg monocrotaline and were then chronically and subcutaneously infused with rat adrenomedullin (PH + AM group, n = 8) or saline (PH group, n = 10) by an osmotic minipump for a period of 21 days. Plasma levels of adrenomedullin were significantly higher in the PH vs. the control group. The chronic infusion of adrenomedullin in rats with pulmonary hypertension increased the plasma levels of adrenomedullin to a value 94% greater than that of the control group and 55% greater than that of the untreated PH group. Chronic infusion of adrenomedullin significantly lessened the increase in right ventricular systolic pressure and the ratio of right ventricular weight to body weight seen after monocrotaline treatment. Histological examination revealed that adrenomedullin also attenuated the medial thickening of the pulmonary artery. These results suggest that chronic infusion of adrenomedullin attenuates the pulmonary hypertension and right ventricular hypertrophy seen in rats treated with monocrotaline.

Adrenomedullin↗
PubMed1998

Effect of adrenomedullin on cAMP and cGMP levels in rat cardiac myocytes and nonmyocytes.

The purpose of the present study was to determine if cardiac myocytes and nonmyocytes secrete adrenomedullin, to investigate the effects of adrenomedullin on cAMP and cGMP levels in cardiac myocytes and nonmyocytes, to study the effect of calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) and adrenomedullin-specific receptor antagonist, adrenomedullin-(22-52) on response to adrenomedullin and CGRP. Neonatal (days 1-2) cardiac myocytes and nonmyocytes were prepared from the ventricle of Wistar rats. Not only cardiac myocytes, but also nonmyocytes secrete almost equal amounts of adrenomedullin into the media. Both adrenomedullin and CGRP increased the cAMP levels, not the cGMP levels, both in the myocytes and nonmyocytes. In myocytes, CGRP-(8-37), almost completely inhibited the adrenomedullin- and CGRP-induced cAMP formation. In nonmyocytes, CGRP-(8-37) completely inhibited the cAMP levels induced by adrenomedullin and CGRP. More profound antagonistic effect of CGRP-(8-37) on cAMP levels induced by adrenomedullin was observed in nonmyocytes than in myocytes. In contrast, antagonistic effect of adrenomedullin-(22-52) for adrenomedullin-stimulated cAMP formation was considerably less potent than CGRP-(8-37) both in myocytes and nonmyocytes. Adrenomedullin-(22-52) did not affect the cAMP formation induced by CGRP either in myocytes or nonmyocytes. These results suggest that myocytes and nonmyocytes secrete adrenomedullin and that adrenomedullin increases cAMP levels possibly via different receptors in myocytes and nonmyocytes.

Adrenomedullin↗
PubMed1998

Plasma natriuretic peptides as indicators of left ventricular remodeling after myocardial infarction.

To investigate the relationship between natriuretic peptides and left ventricular remodeling after acute myocardial infarction, left ventriculography and blood sampling were performed on admission, after 1 month and after 3 months in 33 patients with acute myocardial infarction (15 anterior and 18 inferior). Plasma atrial and brain natriuretic peptide concentrations at 1 and 3 months were higher than those of controls (P<0.01). Brain natriuretic peptide concentrations correlated with changes in left ventricular end-diastolic volume index after 1 and 3 months (1 month: r=0.57, P=0.003; 3 months: r=0.47, P=0.006). Atrial natriuretic peptide concentrations also correlated with changes in left ventricular end-diastolic volume index after 1 and 3 months (1 month: r=0.40, P=0.02; 3 months: r=0.61, P<0.001). Our results indicate that natriuretic peptide concentrations increase in the chronic phase of acute myocardial infarction and may relate to left ventricular remodeling. Thus, atrial natriuretic peptide as well as brain natriuretic peptide concentrations may be useful biochemical markers in identifying asymptomatic patients at risk for heart failure or sudden death after acute myocardial infarction.

Adult↗
PubMed1998

Plasma brain natriuretic peptide is a biochemical marker for the prediction of progressive ventricular remodeling after acute myocardial infarction.

To investigate the relation between plasma brain natriuretic peptide (BNP) and progressive ventricular remodeling, we measured plasma BNP and atrial natriuretic peptide (ANP) in 30 patients with acute myocardial infarction on days 2, 7, 14, and 30 after the onset. Left ventricular end-diastolic volume index (EDVI), end-systolic volume index (ESVI), and ejection fraction (EF) on admission and 1 month after the onset were assessed by left ventriculography. Changes in EDVI (deltaEDVI), ESVI (deltaESVI), and EF (deltaEF) were obtained by subtracting respective acute-phase values from corresponding chronic-phase values. Plasma ANP on days 2 and 7 showed only weak correlations with deltaEDVI (r = 0.48 and 0.54; both p < 0.01), whereas plasma BNP on day 7 more closely correlated with deltaEDVI (r = 0.77; p < 0.001). When study patients were divided into two groups according to plasma BNP on day 7, the group with BNP higher than 100 pg/ml showed greater increases in left ventricular volume and less improvement in EF compared with the other group with BNP lower than 100 pg/ml (deltaEDVI = 10.4 +/- 8 vs -3.4 +/- 9 ml/m2, deltaESVI = 6.2 +/- 7 vs -4.9 +/- 5 ml/m2, and deltaEF = 1.0% +/- 4% vs 4.9% +/- 5%; p < 0.05, respectively). Multiple regression analysis revealed that only plasma BNP on day 7, but not ANP, peak creatine phosphokinase level, left ventricular end-diastolic pressure, or acute-phase EF, correlated independently with deltaEDVI (p < 0.01). These results suggest that plasma BNP may be a simple and useful biochemical marker for the prediction of progressive ventricular remodeling within the first 30 days of acute myocardial infarction.

Adult↗
PubMed1998

Atrial natriuretic peptide secretion and body fluid balance after bilateral atrial appendectomy by the maze procedure.

OBJECTIVES: One of the earliest recognized postoperative complications of the maze procedure was the fluid retention in the immediate postoperative period. Routine postoperative administration of diuretics markedly reduces the frequency and severity of the fluid retention. However, the cause of the abnormal fluid balance is still uncertain. METHODS: We evaluated 24 patients: 15 patients underwent the maze procedure (maze group) and 9 patients did not (nonmaze group). Blood samples were obtained before and in the time course after operation for atrial natriuretic peptide measurement. To evaluate the influence of atrial natriuretic peptide on the body fluid balance, we also measured the amount of body fluid balance and the total doses of furosemide and dopamine administered after operation. To examine the effect of the maze procedure on atrial natriuretic peptide secretion in chronic phase, we measured plasma atrial natriuretic peptide levels during dynamic exercise in 21 patients who had undergone cardiac operations 2 years before. RESULTS: Plasma atrial natriuretic peptide levels in the nonmaze group significantly increased after operation. In contrast, plasma atrial natriuretic peptide levels in the maze group did not increase, and these levels were significantly lower than in the nonmaze group. Although significantly greater doses of furosemide and dopamine were administered to the maze group than to the nonmaze group, the body fluid balance in the maze group was comparable with that in the nonmaze group in the early postoperative period. The response of atrial natriuretic peptide secretion by exercise was significantly attenuated in the maze group (n = 12) compared with the nonmaze group (n = 9) even 2 years after surgery, although there were no significant differences in heart rate or blood pressure during exercise between two groups. CONCLUSIONS: These results suggest that the maze procedure attenuates atrial natriuretic peptide secretion in the early postoperative period and persists in chronic phase. This attenuated atrial natriuretic peptide secretion may reduce the ability of the kidneys to handle fluid load early after surgery.

Atrial Fibrillation↗
PubMed1998

Plasma brain natriuretic peptide levels increase in proportion to the extent of right ventricular dysfunction in pulmonary hypertension.

OBJECTIVES: This study sought to investigate the influence of right ventricular (RV) hemodynamic variables and function on the secretion of brain natriuretic peptide (BNP) in patients with isolated RV overload. BACKGROUND: Plasma BNP is known to increase in proportion to the degree of left ventricular (LV) overload. However, whether BNP secretion is also regulated in the presence of RV overload remains unknown. METHODS: Plasma BNP and atrial natriuretic peptide (ANP) levels in the pulmonary artery were measured in 44 patients with RV overload: 18 with RV volume overload (RVVO) due to atrial septal defect and 26 with RV pressure overload (RVPO) due to primary or thromboembolic pulmonary hypertension. Right heart catheterization was performed in all patients. RV and LV ejection fraction, myocardial mass and volume of the four chambers were determined by using electron beam computed tomography. RESULTS: Although both plasma BNP and ANP levels were significantly elevated in patients with RV overload compared with values in control subjects, plasma BNP and the BNP/ANP ratio were significantly higher in patients with RVPO than with RVVO (BNP 294 +/- 72 vs. 48 +/- 14 pg/ml; BNP/ANP 1.6 +/- 0.2 vs. 0.8 +/- 0.2, both p < 0.05). Plasma BNP correlated positively with mean pulmonary artery pressure (r = 0.73), total pulmonary resistance (r = 0.79), mean right atrial pressure (r = 0.79), RV end-diastolic pressure (r = 0.76) and RV myocardial mass (r = 0.71); it correlated negatively with cardiac output (r = -0.33) and RV ejection fraction (r = -0.71). Plasma BNP significantly decreased from 315 +/- 120 to 144 +/- 54 pg/ml with long-term vasodilator therapy (total pulmonary resistance decreased from 23 +/- 4 to 15 +/- 3 Wood U). CONCLUSIONS: Plasma BNP increases in proportion to the extent of RV dysfunction in pulmonary hypertension.

Adult↗
PubMed1998

Plasma levels of adrenomedullin in patients with acute myocardial infarction.

1. Adrenomedullin, a newly identified vasorelaxant peptide, participates in the regulation of the cardiovascular system. To investigate the pathophysiological significance of adrenomedullin in patients with acute myocardial infarction, we measured plasma levels of adrenomedullin. 2. Cardiac catheterization was performed on admission, after 1 day, and after 4 weeks in 36 patients with acute myocardial infarction. We measured plasma levels of adrenomedullin, atrial natriuretic peptide and brain natriuretic peptide in the right atrium, pulmonary artery and aorta. 3. Plasma levels of adrenomedullin in the right atrium (mean +/- SEM) were significantly increased on admission (4.2 +/- 2.6 h) in patients with acute myocardial infarction (10.6 +/- 1.0 pmol/l) compared with controls (5.2 +/- 0.3 pmol/l, P < 0.01). In addition, plasma levels of adrenomedullin were further elevated in patients with congestive heart failure (12.3 +/- 1.4 pmol/l) compared with patients without congestive heart failure (7.8 +/- 0.6 pmol/l, P < 0.01). In patients with congestive heart failure, plasma adrenomedullin on admission significantly correlated with atrial natriuretic peptide and brain natriuretic peptide. 4. These results suggest that plasma adrenomedullin increases in the early phase of acute myocardial infarction and that volume expansion may be one of the additional stimuli for the release of adrenomedullin in patients with acute myocardial infarction complicated by congestive heart failure.

Adrenomedullin↗
PubMed1998

Increased plasma adrenomedullin concentrations during cardiac surgery.

1. Adrenomedullin (AM), a potent hypotensive peptide, was originally isolated from human phaeochromocytoma. Plasma AM concentrations are elevated in hypertension, heart failure and renal failure in proportion to the severity of the disease. This study was performed to investigate the pathophysiological significance of AM during cardiac surgery. 2. Serial blood samples were obtained from patients undergoing cardiac surgery and plasma AM concentrations were determined by specific radioimmunoassay. 3. Plasma AM concentrations did not increase with anaesthesia or surgery (n = 9). Plasma AM concentrations gradually increased during cardiopulmonary bypass and after pulmonary reperfusion. After pulmonary reperfusion, plasma AM concentrations increased further. In addition, we measured plasma AM concentrations in the pulmonary vein (n = 8) and coronary sinus (n = 8) to examine the contribution of the lungs and heart to the increase in circulating AM concentrations after cardiopulmonary bypass. However, no significant differences were seen in plasma AM concentrations of the pulmonary vein or the coronary sinus and the aorta. Peak AM concentrations during cardiac surgery correlated with duration of surgery. Elevated plasma AM levels during and after surgery began to decline next day after surgery and returned to normal levels 7 days after surgery. 4. These results demonstrate that plasma AM concentrations increase during cardiac surgery and that the duration of surgery may be related to the changes in AM concentrations. Taken together with recent findings that vascular endothelial cells and vascular smooth muscle cells actively produce AM, these results suggest that plasma AM during cardiac surgery may act as a vasodilatory hormone.

Adrenomedullin↗
PubMed1998

Secretion patterns of brain natriuretic peptide and atrial natriuretic peptide in patients with or without pulmonary hypertension complicating atrial septal defect.

UNLABELLED: BACKGROUND This study was designed to investigate plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with atrial septal defect (ASD), whose right ventricular loading patterns vary from simple volume overloading to both volume and pressure overloading. METHODS AND RESULTS: Plasma ANP and BNP in the pulmonary artery were measured in 31 adult patients with ASD and 11 control subjects. On the basis of the presence of pulmonary hypertension (PH, mean pulmonary arterial pressure >20 mm Hg), patients with ASD were divided into two groups, patients without PH (group 1, n = 21) and those with PH (group 2, n = 10). Cardiac catheterization was performed to measure mean pulmonary arterial pressure and pulmonary blood flow. Plasma ANP was significantly higher in both group 1 and group 2 than in the control group. Plasma BNP and BNP to ANP (BNP/ANP) ratio were significantly higher in group 2 than in the control group, although they were not significantly elevated in group 1. Plasma ANP positively correlated with the degree of pulmonary blood flow (r = 0.54, p < 0.01), whereas plasma BNP positively correlated with the magnitude of mean pulmonary arterial pressure (r= 0.73, p < 0.001). BNP/ANP >1 was a powerful marker for the presence of PH (sensitivity 90%, specificity 90%). CONCLUSIONS: Plasma ANP levels were elevated in adult patients with ASD regardless of PH. In contrast, plasma BNP levels were elevated in proportion to the severity of PH complicating ASD. Thus BNP and ANP may represent differing aspects of cardiac response to right ventricular overload in patients with ASD.

Adult↗
PubMed1998

Plasma levels of natriuretic peptides and adrenomedullin in elderly hypertensive patients: relationships to 24 h blood pressure.

OBJECTIVE: The aim of this study was to investigate the relationships between levels of natriuretic peptides and adrenomedullin and 24 h blood pressure levels in elderly hypertensives. DESIGN AND METHODS: We performed both 24 h ambulatory blood pressure monitoring and measurement of plasma levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and adrenomedullin in 118 asymptomatic hypertensive elderly (> 60 years old) patients. We classified the subjects into groups with isolated clinic hypertension (n = 40) and sustained hypertension (n = 78). We also measured the levels of these peptides in 37 elderly normotensive subjects. RESULTS: Plasma ANP and BNP levels were slightly increased in patients with isolated clinic hypertension compared with elderly normotensives. Among the hypertensives, plasma ANP and BNP levels were more closely related to 24 h blood pressure levels than to office blood pressure levels. Sustained hypertensives showed significantly increased plasma levels of ANP and BNP compared with isolated clinic hypertensives, while adrenomedullin levels were similar in the two groups. Elderly hypertensives with left ventricular hypertrophy detected by electrocardiography had significantly higher levels of ANP and BNP, and higher BNP/ANP ratios than those without left ventricular hypertrophy, while there was no significant difference in adrenomedullin levels between the two groups. CONCLUSIONS: Our results suggest that measurements of ANP and BNP may be useful in detecting left ventricular hypertrophy and in differentiating isolated clinic hypertension from sustained hypertension in elderly hypertensive patients.

Adrenomedullin↗
PubMed1998

Increased plasma adrenomedullin levels in patients with acute myocardial infarction in proportion to the clinical severity.

OBJECTIVES: To investigate the pathophysiological role of adrenomedullin in myocardial infarction. PATIENTS AND DESIGN: Plasma concentrations of adrenomedullin, atrial natriuretic factor, and brain natriuretic peptide were measured by radioimmunoassay in 31 patients with acute myocardial infarction over four weeks, and in 44 normal subjects. RESULTS: In patients with acute myocardial infarction, plasma adrenomedullin reached a peak of (mean (SD) 14.0 (9.0) pmol/l at 24 hours after the onset of symptoms and remained increased at all sampling points except the four week point compared with the value in normal subjects (5.0 (2.0) pmol/l). Adrenomedullin concentrations on admission were higher in patients from Killip class II, III, and IV than class I, and correlated positively with peak plasma creatine kinase and left ventricular end diastolic volume index, and negatively with left ventricular ejection fraction. The values from 12 to 48 hours were negatively correlated with systemic vascular resistance index. During the time course studied, adrenomedullin concentrations were positively correlated with atrial natriuretic factor (r = 0.40, p < 0.001) and brain natriuretic peptide (r = 0.53, p < 0.001). CONCLUSIONS: Plasma adrenomedullin concentrations increased in the acute phase of myocardial infarction in proportion with clinical severity suggesting that adrenomedullin may play an important role in the pathophysiology of myocardial infarction.

Adrenomedullin↗
PubMed1998

Production and secretion of adrenomedullin in cultured rat cardiac myocytes and nonmyocytes: stimulation by interleukin-1beta and tumor necrosis factor-alpha.

The present study investigated the secretion level and gene expression of adrenomedullin (AM), a novel vasorelaxant peptide, in cultured neonatal rat cardiac myocytes and nonmyocytes, and the effects of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF alpha) on its production and secretion in these cells. Under serum-free conditions, both myocytes and nonmyocytes secreted immunoreactive (ir-) AM into the culture medium in a time-dependent manner. The secretion rates of ir-AM from myocytes and nonmyocytes per 10(5) cells were almost equivalent. The expression of AM messenger RNA was also observed in cultured myocytes and nonmyocytes. The peptide secretion and messenger RNA level of AM in cardiac myocytes were increased after stimulation with IL-1beta. In nonmyocytes, IL-1beta and TNF alpha remarkably augmented both the release of ir-AM into the medium and AM gene expression after 24 and 48 h of incubation. These observations indicate that cardiac ventricular cells (i.e. myocytes and nonmyocytes) actively produce AM and also suggest that cytokines such as IL-1beta and TNF alpha regulate the gene expression and secretion of this peptide in the ventricles. On the basis of these results and the findings that IL-1beta and TNF alpha are involved in heart failure and cardiac hypertrophy, AM may play a role as an autocrine/paracrine modulator in some cardiac disorders.

Adrenomedullin↗
PubMed1998

Responses of natriuretic peptides to acute and chronic salt loading in normotensive and hypertensive subjects.

Responses of endocrine systems to acute and chronic salt loading were examined in normotensive and hypertensive subjects. In the acute salt load study, isotonic saline (20 ml/kg for 1 h) was intravenously infused in 10 normotensive subjects and 12 patients with essential hypertension. Plasma noradrenaline was suppressed by saline infusion in the normotensive subjects (-19%, p < 0.05), but was not suppressed in the hypertensive patients (-5%, NS). Plasma brain natriuretic peptide concentration was significantly increased in the hypertensive patients (+15%, p<0.05), while it was unchanged in the normotensive subjects. In the chronic salt load study, 9 normotensive subjects and 30 patients with essential hypertension underwent two 7-d periods of 30 and 260 mmol/d sodium intake. On the basis of the blood pressure change, 17 hypertensive patients were classified as salt-resistant and 13 as salt-sensitive. The salt-sensitive hypertensive patients had suppressed plasma renin activity even during low-salt intake. During high salt intake, the plasma noradrenaline concentration failed to decrease in the salt-sensitive hypertensive patients (-6%, NS), whereas it fell significantly in the normotensive subjects (-27%, p < 0.05) and the salt-resistant hypertensive patients (-33%, p < 0.01). The high-salt intake also increased plasma concentrations of brain natriuretic peptide as well as atrial natriuretic peptide in all groups. In the salt-sensitive hypertensive patients, there was a positive correlation between the increase in blood pressure and that in atrial natriuretic peptide (r= 0.84, p< 0.01). These data indicate that brain natriuretic peptide is involved in chronic changes in body fluid volume. In patients with essential hypertension, acute volume expansion also evokes the response of brain natriuretic peptide. Salt-sensitive hypertension seems to be characterized by blunted response of the sympathetic nervous system. In addition, an increase in atrial natriuretic peptide is likely to play an important role in mechanisms counteracting salt-induced elevation of blood pressure.

Adult↗