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ABSTRACT: PurposeTo clarify the relationships between spontaneous echo contrast (SEC) detected by transesophageal echocardiography (TEE) and
coagulopathy, ultrasonographic findings that may correlate to biochemical coagulation markers were examined.
MethodsTEE was performed on 49 consecutive patients (mean age 64 ± 14 years; 28 men, 21 women). Blood samples were taken at the same
time as TEE was carried out. Aortic SEC (Ao-SEC) and left atrial SEC (LA-SEC) were classified into three grades: absent, mild
and marked. Levels of von Willebrand factor (vWF), thrombin antithrombin III complex (TAT), prothrombin fragments 1+2 (F1+2)
and fibrinopeptide A (FPA) were measured.
ResultsMean plasma vWF levels by Ao-SEC grade were 144 ± 39% for absent, 177 ± 55% for mild and 210 ± 73% for marked, with significantly
higher levels in the Ao-SEC marked group than in the Ao-SEC absent group (P < 0.05). Mean plasma vWF levels by LA-SEC were 185 ± 73% for absent, 180 ± 49% for mild and 201 ± 62% for marked, with no
significant differences apparent between groups. Moreover, no relationships were identified between Ao-SEC grade and plasma
levels of coagulation indicators TAT, F1+2 and FPA.
ConclusionPlasma vWF levels correlated to grade of aortic SEC. Characteristics of the coagulation system differ between Ao-SEC and LA-SEC.
Ao-SEC offers a clinical indicator of platelet thrombus formation.
Journal of Medical Ultrasonics 04/2012; 33(4):225-230. · 0.33 Impact Factor
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ABSTRACT: Loop diuretics are essential for the treatment of chronic heart failure (CHF) but short-acting diuretics are reported to induce sympathetic nervous system (SNS) activation. This study was performed to compare therapeutic effects of two loop diuretics, long-acting azosemide and short-acting furosemide, using (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy.
Twenty-two patients with New York Heart Association class II-III heart failure and left ventricular dysfunction, who required treatment with a loop diuretic, were included. In this crossover study, 11 patients were randomized to azosemide treatment first and the remaining 11 patients to furosemide. Treatments were administered for 6 months and then patients were crossed over to the second treatment. (123)I-MIBG scintigraphy was performed before and 6 months after the start of treatment with each loop diuretic. Early and delayed images were obtained 20 min and 4 h after administration of (123)I-MIBG, respectively; and the heart/mediastinum (H/M) ratio and washout rate (WR) were measured. In addition, left ventricular ejection fraction (LVEF), levels of brain natriuretic peptide (BNP), and norepinephrine were measured before and 6 months after the start of treatment. No differences were observed between the two groups in terms of concomitant medication, cause of heart failure, H/M ratio, WR, BNP, norepinephrine, or LVEF. The azosemide group exhibited a significant increase in delayed image H/M ratio, and a significant decrease in WR and norepinephrine after the final administration compared with the furosemide group.
This study indicates that azosemide suppresses SNS activation compared with furosemide in patients with CHF, suggesting that long-acting loop diuretics may have more beneficial effects on the prognosis of CHF.
European Journal of Heart Failure 05/2011; 13(8):892-8. · 4.90 Impact Factor
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Yoichiro Okubo,
Kazutoshi Shibuya, Atsushi Namiki,
Kazuhisa Takamura,
Noriaki Kameda,
Tetsuo Nemoto,
Aki Mitsuda,
Megumi Wakayama,
Minoru Shinozaki,
Nobuyuki Hiruta,
Kanako Kitahara,
Takao Ishiwatari,
Junichi Yamazaki
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ABSTRACT: Leiomyosarcoma occurring as a primary cardiac tumor has been known as an extremely rare condition. Previous studies of leiomyosarcoma with rhabdomyoblastic differentiation have conducted to those arisen from another site, and they indicated a poorer prognosis of this tumor.
A 69-year-old woman was referred to our hospital for an operation concerning umbilical hernia. Subsequent imaging examinations before an operation indicated the presence of primary cardiac malignant tumor due to its atypical shape. And then, it was surgically removed. Histopathologically, tumor cells consisted of two different types: spindle and polyhedral cells. Immunohistochemically, it is interesting to note that 2.1% of spindle cells and 23.1% of polyhedral cells showed positive reactivity for myogenin. Furthermore, we performed double-immunostaining for alpha-smooth muscle actin (SMA) and myogenin. The rates of alpha-SMA and myogenin double negative, alpha-SMA single positive, myogenin single positive, and alpha-SMA and myogenin double positive in spindle cells were estimated as 69.1%, 28.8%, 1.1% and 1.0%, respectively. In contrast, the rates in polyhedral cells were estimated as 76.9%, 0.0%, 23.1%, and 0.0%, respectively.
Our immunohistochemical evaluation suggested that rhabdomyoblastic differentiation in leiomyosarcoma might be generated not only by de novo generation from mesenchymal cells. To the best of our knowledge, this is the first case of primary cardiac leiomyosarcoma with partial rhabdomyoblastic differentiation.
BMC Cancer 02/2011; 11:76. · 3.01 Impact Factor
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ABSTRACT: Recent development of multi-detector computed tomography (MDCT) has made the detection of myocardial bridge (MB) easier on the left anterior descending coronary artery (LAD). The LAD segment proximal to the MB is well known to be susceptible to atherosclerosis. Anatomical characteristics of MB on LAD in patients with myocardial infarction (MI) were examined by MDCT.
Subjects were 43 MI patients who had MB in the LAD and comprised 2 groups: 14 with culprit lesions in the LAD proximal to MB (culprit group) and 29 without culprit lesions in the LAD (non-culprit group). MB length, MB thickness, and the distance from the orifice of left main trunk (LMT) to MB entrance were compared. Age and coronary risk factors showed no significant difference between the 2 groups. MB length (P=0.011), MB thickness (P=0.035), and index of the length multiplied by thickness of MB (P=0.031) were significantly greater in the culprit group. The distance from the orifice of the LMT to MB entrance was significantly shorter in the culprit group (P=0.006).
Anatomical properties of MB, such as length and thickness of MB as well as MB location, are associated with the formation of culprit lesions of LAD proximal to MB in MI.
Circulation Journal 01/2011; 75(3):642-8. · 3.77 Impact Factor
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ABSTRACT: Although it has been reported that (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is useful for assessing the prognosis of dilated cardiomyopathy (DCM), there have been no reports regarding how interval MIBG imaging should be performed during follow-up. We investigated the significance of performing MIBG at different times for the long-term prediction of cardiac events in DCM patients.
The participants were 36 DCM patients who did not sustain cardiac events for 2 years after beta-blocker induction. MIBG was performed 6 months and 2 years after beta-blocker induction and the images analyzed to obtain the extent score, severity score (SEV), and the washout rate. Echocardiography was performed at the same time.
Eight patients experienced a cardiac event during follow-up (cardiac death: two patients; heart failure requiring hospitalization: six patients). Although no significant difference was found in any MIBG parameters or left ventricular ejection fraction between patients who experienced a cardiac event and those who did not after 6 months, early extent score, early SEV, delayed SEV, and washout rate were found to be significantly higher for patients who experienced a cardiac event after 2 years. In multivariate analysis using Cox proportional hazard model, none of the MIBG parameters or left ventricular ejection fraction after 6 months was identified as a predictor of cardiac events. However, delayed SEV after 2 years (hazard ratio 1.067, P = 0.0435) was a significant predictor of cardiac events.
The study suggested that performing MIBG at least once every 2 years allows long-term prediction of cardiac events in the follow-up of DCM patients.
Nuclear Medicine Communications 06/2010; 31(6):488-94. · 1.40 Impact Factor
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ABSTRACT: The distribution of left ventricular (LV) fibrosis and the percent fibrosis in patients with dilated cardiomyopathy (DCM) were evaluated using late gadolinium enhanced (LGE) MRI. Then the relation with the LV ejection fraction (EF) and deceleration time (DT), an index of diastolic function obtained using echocardiography, was investigated.
LGEMRI at 20 min after intravenous injection of Gd-DTPA (0.15 +/-0.03 mmol/kg) was performed in 17 patients with DCM. The distribution of the LV enhanced area and LGE rate (%) were calculated. EF, as well as E/A ratio and DT were obtained using echocardiography. LGE was observed in 15 out of 17 patients (88%) and the enhanced region appeared to represent myocardial fibrosis. The LV fibrosis was often found in the intraventricular septum (IVS), but there were no differences in its distribution. The LGE rate (%) had a correlation between cardiac magnetic resonance ejection fraction (CMREF) (Y = 51.7 - 2.1X [R(2) = 0.23, P<0.001]) and DT (Y = 162.2 +12.0X [R(2) = 0.35, P<0.001]).
The LV fibrosis is often found in the IVS with DCM. A correlation exists between LGE rate (%) to EF on CMR and DT on echocardiography in patients with DCM.
Circulation Journal 09/2009; 73(10):1939-44. · 3.77 Impact Factor
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ABSTRACT: Because increased sympathetic nervous activity (SNA) in patients with dilated cardiomyopathy (DCM) associated with sleep breathing disorder (SBD) is known to deteriorate the prognosis of cardiac failure, (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was used as the investigative tool in the present study.
The study group comprised 53 patients (47 men, 6 women; mean age 56+/-3 years) with chronic stable DCM. Patients were divided into SBD(+) or SBD(-) group according to 24-h pulse oximetry results. SBD(+) was defined when the 3% oxygen desaturation index was more than 15/h during sleep. In total, 32 patients were SBD(-) and 21 were SBD(+). In both groups, pulse oximetry were performed during sleep and awakening pulse rate, and measurement of the blood levels of catecholamines and B-type natriuretic peptide was performed. MIBG myocardial scintigraphy and echocardiography were performed at the same time. No significant difference was found between the 2 groups in catecholamine levels or left ventricular ejection fraction. However, MIBG had a significantly increased washout rate and a significantly decreased delayed heart to mediastinum ratio in the SBD(+) group compared with the SBD(-) group.
SNA is increased in DCM patients when associated with SBD. MIBG myocardial scintigraphy may be a sensitive method of detecting increased SNA.
Circulation Journal 05/2009; 73(4):686-90. · 3.77 Impact Factor
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ABSTRACT: Basic fibroblast growth factor (bFGF) inhibits the progression of ventricular remodeling in ischemic and hypertensive heart diseases (HHDs). Recent studies have revealed that bFGF induces the transition from myofibroblasts to fibroblasts with decreased expression of alpha-smooth muscle actin (alpha-SMA). To clarify the mechanisms underlying the reduced ventricular remodeling in hypertensive heart diseases caused by bFGF, we examined the degree of interstitial fibrosis associated with alpha-smooth muscle actin expression and matrix metalloproteinase activity in hypertensive heart diseases.
Dahl salt-sensitive rats were fed with a high-salt diet from 6 to 18 weeks of age and injected with a single dose of bFGF (100 microg) into the left myocardium at 15 weeks. Others were administered PBS without bFGF. Control age-matched Dahl salt-sensitive rats were fed with a low-salt diet.
Cardiac systolic function was well preserved and decompensation of heart failure was prevented at 18 weeks in the rats treated with bFGF at 15 weeks. The bFGF-treated rats had significantly fewer interstitial alpha-SMA-positive myofibroblasts and significantly decreased prolyl 4-hydroxylase expression. Increased matrix metalloproteinase-9 gelatinase activity correlated with the downregulation of transforming growth factor-beta1 by bFGF, suggesting that inhibited extracellular matrix deposition is associated with a decreased number of myofibroblasts induced by bFGF.
bFGF can inhibit the progression of ventricular remodeling by inhibiting interstitial fibrosis and promoting angiogenesis without decreasing blood pressure in hypertensive heart disease.
Journal of Hypertension 01/2009; 26(12):2436-44. · 4.02 Impact Factor
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Atsushi Namiki
Nippon rinsho. Japanese journal of clinical medicine 09/2007; Suppl 4:25-8.
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ABSTRACT: The aim of this study was to assess the effects of hydrophilic pravastatin and lipophilic atorvastatin on glucose metabolism and lipid metabolism in non-diabetic patients with hypercholesterolemia.
Fasting plasma glucose (FPG), hemoglobin A(1c) (HbA(1c)), total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), and triglyceride (TG) levels were determined before and after statin treatment.
A total of 44 nondiabetic patients (FPG < or =125 mg/mL; HbA(1c) <5.8%) undergoing treatment with either pravastatin (n=21) or atorvastatin (n=23) for hypercholesterolemia were investigated.
FPG level in the pravastatin but not atorvastatin group was significantly lowered after vs before treatment. Accordingly, the HbA(1c) level in the atorvastatin but not in the pravastatin group was significantly increased. As expected, both TC and LDL-C levels were significantly lowered in both groups. In particular, the TC level in the atorvastatin group was more remarkably and significantly improved than in the pravastatin group. On the other hand, the HDL-C level in the pravastatin group but not in the atorvastatin group was significantly increased after the administration period. The TG level was unaffected in both groups.
Pravastatin was suggested to act favorably, while atorvastatin adversely, regarding it's effects on glucose metabolism in nondiabetic hypercholesterolemic patients, although atorvastatin exerted more potent cholesterol-lowering effects compared with pravastatin.
Internal Medicine 01/2006; 45(2):51-5. · 0.94 Impact Factor
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ABSTRACT: A reduction of coronary flow reserve has been reported in patients with hypertensive heart disease (HHD), which suggests that myocardial ischemia may contribute to the progression to cardiac failure in HHD. Therefore, we evaluated whether fibroblast growth factor (FGF)-2 and/or heparin, which induce angiogenesis, may affect cardiac function in the setting of HHD. We used Dahl salt sensitive (DS) rats as an HHD model. Direct intramyocardial injection of 100 microg of FGF-2 plus 1.28 microg of heparin (n = 6), 100 microg of FGF-2 (n = 6), 1.28 microg of heparin (n = 6) or saline (n = 6) were performed in 9-week-old rats. Echocardiography was performed to evaluate cardiac function at 9, 11, and 13 weeks of age. Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations were measured at 8 and 13 weeks of age. DS rats were killed 4 weeks after myocardial injection (at 13 weeks of age), and myocardial capillary density was assessed by von Willebrand factor staining. Injection of FGF-2 plus heparin significantly decreased left ventricular end-diastolic diameter (P < 0.0001) and left ventricular end-systolic diameter (P < 0.0001), significantly improved the reduction of left ventricular fractional shortening (P = 0.0005), significantly decreased plasma ANP (P < 0.0001) and BNP (P = 0.016) concentrations, and significantly increased myocardial capillary density (P = 0.0002) compared with injection of saline. These findings indicate that intramyocardial injection of FGF-2 plus heparin suppresses the progression of cardiac failure in DS rats. FGF-2 plus heparin administration may be a new therapeutic strategy for the treatment of HHD.
International Heart Journal 04/2005; 46(2):289-301. · 1.16 Impact Factor
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ABSTRACT: Some angiogenic factors, including hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF), have been reported to promote angiogenesis and improve myocardial perfusion in experimental models of ischemic heart disease. These factors are produced in various tissues, including myocardium. We measured the concentrations of HGF, bFGF, and VEGF by enzyme-linked immunosorbent assay in plasma and in pericardial fluid sampled during open heart surgery (12 patients with ischemic heart disease and 17 with nonischemic heart disease). HGF levels were significantly higher in plasma than in pericardial fluid (12.0 +/- 1.8 versus 0.26 +/- 0.04 ng/mL, P < 0.0001). On the other hand, bFGF levels were significantly higher in pericardial fluid than in plasma (243.5 +/- 50.9 versus 49.6 +/- 7.8 pg/mL, P = 0.009). VEGF levels were not significantly different between pericardial fluid and plasma (47.2 +/- 17.6 versus 24.5 +/- 3.6 pg/mL, P = 0.23). Concentrations of angiogenic factors in pericardial fluid and in plasma were not significantly different between patients with ischemic and nonischemic heart disease. These results suggest that the production, secretion, and kinetics of HGF, bFGF, and VEGF are different. These angiogenic factors may have different pathophysiologic roles.
Japanese Heart Journal 12/2004; 45(6):989-98. · 0.40 Impact Factor
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Nippon rinsho. Japanese journal of clinical medicine 10/2004; 62 Suppl 9:469-73.
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ABSTRACT: Recent studies have shown that percutaneous coronary intervention (PCI) activates systemic hemostatic activity, reflecting platelet activation and thrombin formation in the coronary arteries. The present study compared systemic levels of hemostatic markers induced by plain old balloon angioplasty (POBA), coronary stenting (STENT), and cutting balloon (CB) angioplasty. Sixty-one patients with stable angina pectoris, who underwent elective PCI or diagnostic coronary angiography (CAG) alone, were investigated. Patients who underwent PCI were divided into the POBA group (n = 11), the STENT group (n = 27), and the CB group (n = 11). Patients who underwent CAG alone were assigned to the CAG group (n = 12). Blood samples were collected before, 24 hours after, and 3 days after PCI or CAG. Plasma concentrations of prothrombin fragment 1+2 (F1+2), fibrinopeptide A (FPA), thrombin-antithrombin III complex (TAT), and plasminogen activator inhibitor-1 (PAI-1) were measured. In the CB group, the F1+2 (1.23 +/- 0.4 nmol/L) level 3 days after PCI was significantly smaller than that of the POBA group (2.37 +/- 0.5 nmol/L) (P < 0.05). The FPA (1.81 +/- 0.9 ng/mL), TAT (3.36 +/- 1.2 ng/mL) and PAI-1 (23.0 +/- 4.1 ng/mL) levels in the CB group 3 days after PCI were significantly smaller than those of the POBA group (P < 0.05, respectively) and STENT group (P < 0.05, respectively), but similar to the CAG group. Systemic hemostasis is activated to a greater extent after POBA and stenting than it is after CB angioplasty of the coronary arteries. This may contribute to the favorable long-term outcome of CB angioplasty.
Japanese Heart Journal 06/2004; 45(3):409-17. · 0.40 Impact Factor
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ABSTRACT: There is epidemiologic evidence that the prognosis of patients with nonischemic heart failure is better than that for patients with ischemic heart failure. In addition, studies have revealed that patients with ischemic heart failure show a poorer response to medical therapy. However, the pathophysiologic difference between ischemic and nonischemic heart disease is unclear. To clarify this point, we measured atrial natriuretic peptide, brain natriuretic peptide, angiotensin II, endothelin (ET)-1. interleukin-1beta interleukin-6. tumor necrosis factor (TNF)-alpha soluble TNF receptor I, and soluble TNF receptor II concentrations in plasma and pericardial fluid in patients with ischemic or nonischemic heart disease undergoing cardiac surgery. The pericardial ET-1 concentration in patients with ischemic heart disease was statistically greater than that in patients with nonischemic heart disease (about 1.5-fold), although no difference was found in the plasma ET-1 concentration. These findings suggest that the production and secretion of ET-1 from the myocardium in patients with ischemic heart disease are augmented to a greater extent than in patients with nonischemic heart disease. This result may lead to a greater understanding of the pathophysiology of ischemic heart disease.
Japanese Heart Journal 10/2003; 44(5):633-44. · 0.40 Impact Factor
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Tetsuya Kubota,
Naoto Kubota,
Masao Moroi,
Yasuo Terauchi,
Tsuneo Kobayashi,
Katsuo Kamata,
Ryo Suzuki,
Kazuyuki Tobe, Atsushi Namiki,
Shinichi Aizawa,
Ryozo Nagai,
Takashi Kadowaki,
Tetsu Yamaguchi
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ABSTRACT: Insulin resistance is associated with atherosclerosis, but its mechanism is unknown. It has been reported that insulin receptor substrate (IRS)-1 deficient (IRS-1-/-) mice showed insulin resistance without type 2 diabetes, whereas the IRS-2 deficient (IRS-2-/-) mice showed insulin resistance with type 2 diabetes.
We investigated neointima formation in the IRS-1-/- and IRS-2-/- mice at 8 and 20 weeks. The IRS-2-/- mice showed much greater neointima formation than the IRS-1-/- and wild-type mice at 8 weeks. At 20 weeks, the IRS-2-/- mice had greater neointima formation than the IRS-1-/- mice, which showed more enhanced neointima formation than the wild-type mice. The IRS-1-/- and IRS-2-/- mice had dyslipidemia, hypertension, and insulin resistance. The IRS-2-/- mice had more metabolic abnormalities than the IRS-1-/- mice at 8 and 20 weeks. IRS-2 expression was detected, but IRS-1 expression was not detected in the vessels.
The neointima formation in the IRS-1-/- and IRS-2-/- mice appears to be related to abnormalities induced by the altered metabolic milieu in insulin-resistant states. Moreover, because neointima formation was much greater in the IRS-2-/- mice than in the IRS-1-/- mice at 8 and 20 weeks, it is suggested that a lack of IRS-2 renders the vasculature more susceptible to injury in the abnormal metabolic milieu, and IRS-2 may have a protective effect on neointima formation. We conclude that IRS-2 is protective and retards the development of neointima formation in insulin-resistant states.
Circulation 07/2003; 107(24):3073-80. · 14.74 Impact Factor
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ABSTRACT: A 69-year-old man was admitted with palpitations and syncope. His medical history included hypertension and left ventricular hypertrophy. Arterial pulsation was not palpable on admission. Electrocardiography revealed ventricular tachycardia, and cardioversion restored normal sinus rhythm. An electrophysiological study reproducibly induced polymorphic ventricular tachycardia, so a cardioverter defibrillator was implanted. Echocardiography revealed mid-ventricular obstruction and an apical aneurysm, and Doppler color flow imaging showed a diastolic paradoxic jet from the apex toward the base. Coronary angiography showed no stenosis of the extramural coronary arteries. Ventricular tachycardia on admission showed a right bundle branch block pattern and a superior axis deviation, so the arrhythmia was thought to originate from the apical aneurysm. Apical aneurysm can result from elevated intraventricular pressure or relative myocardial ischemia. This is a rare case of hypertrophic cardiomyopathy with mid-ventricular obstruction complicated with apical aneurysm and polymorphic ventricular tachycardia.
Journal of Cardiology 05/2002; 39(4):213-9. · 1.28 Impact Factor
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ABSTRACT: A 66-year-old woman admitted with dyspnea on exertion had atrial fibrillation and left ventricular dysfunction. Echocardiography revealed an atrial septal defect (ASD) and a soft, easily deformable thrombus in the dilated left atrium. The atrial mass suddenly disappeared on the 10th day after admission, and contrast-enhanced chest computed tomography and pulmonary blood flow scintigraphy showed that the thrombus had detached from the left atrium, floated into the right atrium through the ASD and caused pulmonary embolism. This is the first documented case of a left atrial thrombus causing pulmonary embolism by passing through an ASD. When an ASD is present, it is important to consider not only paradoxical thromboembolism (from the right to the left atrium), but also pulmonary embolism caused by thromboembolism from the left to the right atrium.
Circulation Journal 02/2002; 66(1):109-10. · 3.77 Impact Factor
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ABSTRACT: Age-related changes in the effect of parathyroid hormone-related protein (PTHrP) on the cytosolic free calcium level ([Ca+]i) and on the tension in rat aortic smooth muscle were investigated. The possible involvement of cAMP, a second messenger of PTHrP, in such changes was also investigated. Spiral aortic strip preparations without endothelium from 8-weeks, 6-months, and 24-months old rats were treated with fura 2/AM, and the fluorescence ratio R340/380, an index of [Ca+]i was measured. Simultaneously, the tension of the preparations was measured. PTHrP-(1–34) and dibutyryl cAMP produced concentration-dependent decreases in the tension and in R340/380 in aortas precontracted with phenylephrine (10–7 M). These effects were significantly lower in the aortas of 24-months old rats than in the vessels of 8-weeks and 6-months old rats. The effects were similar in the aortas of 8-weeks and 6-months old rats. PTHrP-(1–34) concentration-dependently increased cAMP production in vascular smooth muscle cells (VSMCs) from 8-weeks old rats. However, the increase in cAMP production was significantly lower in cultured VSMCs from 6-months and 24-months old rats than in cells from 8-weeks old rats.These results suggest that the reduced cAMP production stimulated by PTHrP and the reduced effects of cAMP with aging might contribute to the age-related changes in the decreases in tension and [Ca+]i in response to PTHrP in the rat aorta.
Archiv für Experimentelle Pathologie und Pharmakologie 01/1995; 351(5):517-522. · 2.65 Impact Factor
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ABSTRACT: The vascular contractile mechanism of prostacyclin (PGI2) was investigated using beraprost sodium (BPS), a stable PGI2 analog. Ring strips without endothelium isolated from canine femoral veins and arteries were used. BPS induced a dose-dependent contraction without precontraction and after precontraction with norepinephrine (NE) or 60 mM K+ in the veins. In contrast, BPS induced a dose-dependent relaxation after precontraction with U46619, a thromboxane A2 (TXA2) analog, or prostaglandin F2 (PGF2) in the veins. In the arteries, BPS induced contraction at higher concentrations after precontraction with NE. However, BPS relaxed arteries dose-dependently after precontraction with PGF2. By pretreatment with 13-azaprostanoic acid (13-APA), a TXA2/endoperoxide receptor antagonist, the dose-response curve of BPS in the veins was shifted to the right. Schild plot analysis resulted in a linear regression with a slope of 0.86 0.13, which was not significantly different from unity, and the pA2 value for 13-APA against BPS was 7.10 0.06. By pretreatment with BPS, the dose-response curve of U46619 in the veins was shifted to the right. Kaumann plot analysis resulted in a linear regression with a slope of 0.89 0.09, which was not significantly different from unity, and the pA2 value for BPS against U46619 was 5.68 0.04. These findings indicate that BPS is a partial agonist for the TXA2/endoperoxide receptors.
Heart and Vessels 12/1993; 9(1):14-18. · 2.05 Impact Factor
