Specific binding sites for bradykinin and its degradation process in cultured rat vascular smooth muscle cells.
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Biomedical subjects
Publications and source records attributed to S Takata.
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A 65-year-old man was admitted with chest pain. A diagnosis of spastic angina was made because of symptoms of recurrent anginal attacks associated with ST-segment elevations in the electrocardiogram. A selective coronary arteriogram revealed a 90% diameter narrowing of the proximal left anterior descending coronary artery (LAD). No angiographically visible collaterals from the right coronary artery to the LAD were observed. The ventriculogram showed normal contraction of the left ventricle with an ejection fraction of 65%. Percutaneous transluminal coronary angioplasty (PTCA) failed resulting in total occlusion of the stenosis. Repeat PTCA at a higher pressure and of longer duration failed to redilate the artery. Reperfusion with the blood from the femoral artery through the balloon catheter, which was used for the PTCA, was carried out until coronary artery bypass grafting (CABG). Blood flow rate of perfusion was approximately 25 ml/min. Reperfusion through the balloon catheter reduced chest pain and ST-segment elevations in the electrocardiogram. The patient tolerated the operative procedure well and his post-operative course was uncomplicated. The interval between the acute occlusion and revascularization by CABG was approximately 4 1/4 h. The ventriculogram taken 56 days after the CABG demonstrated normal contraction of the anterior wall of the left ventricle with an ejection fraction of 63%. Abnormal Q waves did not appear in precordial leads of the electrocardiogram after the surgery. The thallium scintigram showed no perfusion defects. In conclusion, this case suggested that autologous blood reperfusion through balloon catheter would be worth attempting in some cases for minimization of myocardial infarction during the interval between failed PTCA and emergency CABG.
1. The effects of sodium loading on cardiopulmonary baroreflex control of forearm vasoconstriction were studied using lower body negative pressure (LBNP) in 12 healthy young subjects. 2. Before and during sodium loading, there was no significant change in mean blood pressure, heart rate, central venous pressure (CVP) or forearm vascular resistance (FVR). 3. The degree of reflex increase in FVR during LBNP at -10, -20, and -40 mmHg was significantly greater during sodium loading than regular diet. 4. During sodium loading, the slope of the regression line relating percent change in FVR and change in CVP was significantly increased. 5. These results suggest that sodium loading augments cardiopulmonary baroreflex sensitivity of FVR in normotensive subjects without a family history of hypertension.
1. To clarify whether acute changes in the properties of baroreflexes can occur in man, we evaluated the time course of baroreflex control of heart rate and cardiopulmonary baroreflex control of forearm vascular resistance (FVR) over 240 min after intravenous administration of propranolol (0.2 mg/kg) in 13 healthy young men. 2. Systolic and diastolic blood pressure remained unchanged after propranolol. Propranolol significantly decreased cardiac index and heart rate, and significantly increased total peripheral resistance. These effects remained unchanged for 240 min after propranolol. 3. Baroreflex control of heart rate was significantly augmented immediately after, and at 30, 60 min after propranolol, but partly reverted to the initial level afterwards. Cardiopulmonary baroreflex control of FVR was reduced immediately after, and at 30, 60 min after propranolol, but partly reverted to the initial level afterwards. Pressor responses to phenylephrine was reduced immediately after propranolol, but no significant differences were observed after 30 min. 4. These results suggest that acute changes in the properties of baroreflexes occur in man after propranolol.
To determine whether cholinergic mechanisms contribute to blood pressure regulation, we examined the effects of atropine on pressor responses to phenylephrine and vasoconstrictor responses to the cold pressor test (CPT) and lower body negative pressure (LBNP) in 16 healthy subjects. Heart rate, blood pressure and cardiac index were significantly increased, and central venous pressure (CVP) was significantly decreased after atropine (0.04mg/kg). After atropine, pressor responses to phenylephrine at doses of 20, 40 and 80 micrograms were significantly increased by 101, 112 and 93% (p less than 0.001); however, atropine attenuated pressor responses to CPT (p less than 0.001) and forearm vasoconstrictor responses to LBNP. In 6 propranolol-treated subjects, atropine also augmented pressor responses to phenylephrine but attenuated pressor responses to CPT. These results suggest that atropine augments the pressor response to an alpha-agonist, which may be partly explained by inhibition of compensatory vascular responses mediated by cholinergic mechanisms.
Nineteen surgically treated intrathoracic vagus nerve tumors (16 neurilemmomas, 3 neurofibromas), including three treated by the authors, were reviewed. Tumor resection with vagus nerve amputation was performed in 14 and intracapsular excision without nerve amputation in 3 of the 17 adequately recorded cases. The location of vagus nerve tumor was the left upper mediastinum in 11 patients, almost all of whom were hoarse postoperatively due to sacrifice of the recurrent laryngeal nerve.
Single coronary artery has been considered a minor coronary anomaly without clinical importance. With the wide spread of coronary angiography, however, the disease has been reported to develop complications at a high rate, such as angina, myocardial infarction and arrhythmia. We report three patients with single coronary artery with several complications. Case 1: A 56-year-old woman having a past history of diabetes mellitus and myocardial infarction was admitted because of the recently developed frequent attacks of effort angina. Treadmill test was positive and thallium-201 exercise myocardial scintigraphy revealed redistribution in the lateral wall. Ascending aortogram suggested that the right coronary artery (RCA) arose from the left sinus of Valsalva. An injection into the right sinus of Valsalva revealed no coronary ostium. Selective left coronary angiogram resulted in the diagnosis of single coronary artery (Smith's type 2) with 90% stenosis in the left circumflex artery (LCX). Left ventriculogram showed hypokinesis in the anterolateral wall. PTCA performed on this patient revealed clinical and nucleomedical improvement. Case 2: A 48-year-old man experienced chest pain and syncope. Electrocardiogram revealed ST-elevations in II, I and a VF, sinus bradycardia and atrioventricular junctional rhythm. Angiography resulted in the diagnosis of single coronary artery (Smith's type 2) with 75% stenosis in the RCA. Ergonovine test was positive. Case 3: A 69-year-old man complained of chest pain. Electrocardiogram showed complete right bundle branch block, sinus bradycardia and atrioventricular junctional rhythm. Cardiac catheterization revealed that this was also a case of single coronary artery (Smith's type 2) with no significant stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)
In this report, we described our surgical experiences of Ebstein's anomaly with severe tricuspid stenosis (TS) or regurgitation (TR). Long-term clinical assessments and late problems of the treatment were also mentioned. From 1953 to 1988, a total of 2850 patients with congenital heart malformation underwent surgery in our hospital. During this period, 32 patients with Ebstein's anomaly were admitted, and surgical treatment was performed in 10 of these patients. Thus, the surgical treatment of Ebstein's anomaly took only 0.35% of total surgeries of congenital heart diseases. According to Takayasu's classification of Ebstein's anomaly, 6 of our these patients were classified into TS, and 4 into TR type. The operative methods were shunt operation in 3 patients, plication in 2 patients and tricuspid valve replacement (TVR) in 5 patients. One patient was died during the operative course of Glenn's procedure. Other 9 patients are alive and the longest follow-up period is 18 years at this moment. In the remaining two patients with shunt operation, Blalock-Taussig's procedure completely diminished their polycythemia. In the cases of TVR, the replaced valve was sutured to the right atrium in 2 patients with TS, true annulus in 2 patients with TR, valve remnant in one patient with TR type. Delayed cardiac tamponade occurred in 2 patients and calcification of Xenograft valve was observed at 8 years after the surgery in one patient with TVR. Although the hemodynamics did not improve immediately just after open heart surgery, cardio-thoracic ratio reduced and clinical symptoms were improved remarkably throughout the long-term follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
A-62-years-old man was admitted our hospital because of angina at rest and during effort. Coronary angiography revealed 25% fixed stenosis in Seg. 6, 90% in Seg. 7, 75% in Seg. 10, and 50% in Seg. 12. Percutaneous transluminal angioplasty was performed for segment 7 and complete revascularization was obtained finally. Two and a half months later, progressive lesion occurred in the segment proximal to the angioplasty site (Seg. 6). The manipulation of the guiding catheter in the coronary artery proximal to the PTCA site might have developed atherogenesis in this area. So we must consider the possibilities of both restenosis and new lesions when one has the recurrence of ischemic symptoms after coronary angioplasty.
Eighteen cases of mycotic lung disease, which included 17 pulmonary aspergillosis and one cryptococcosis, were treated surgically. Lobectomy was performed in 4, segmentectomy in 1, partial resection of lung in 4, cavernostomy in 2, open window thoracotomy in 4 and exploratory thoracotomy in 1. The authors would like to emphasize following points; 1) Of eighteen, cases, there were five patients over 70 years old and results of surgery in those were uneventful. 2) Two cases developed the postoperative empyema which was caused by the remnant lesion invaded with aspergillus fumigotus. From this experience it was considered that in the invasive aspergillosis the limited resection of the lesion was not recommended because of its local recurrence. 3) Omentopexy was effective for the treatment of mycotic empyema.
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The mechanism of muscle fatigue was studied by 31P-MRS. During tetanic contraction for 2 minutes(min), the tension measured with a strain gauge and Phosphocreatine(PCr)/Inorganic phosphate(Pi)+ Phosphomonoester(PME) ratio decreased to 31.5 +/- 4.4% of the control value and 0.6 +/- 0.1, respectively. The intracellular pH(pH) also decreased to 6.62 +/- 0.04. Toward the end of the stimulation, the tension decreased to 25.3 +/- 1.9% of the control value. However, during 20min stimulation, the PCr/(Pi+PME) ratio increased to 2.5 +/- 0.5 and the pH to 6.91 +/- 0.04. These results show that muscular fatigue is ascribable not to a decreased level of high energy metabolites required for actomyosin ATPase, but to an increase in the threshold intensity of excitation in excitation-contraction coupling.
Specific binding sites for synthetic porcine endothelin (pET), a novel potent vasoconstrictor peptide isolated from the supernatant of cultured porcine endothelial cells, and its effects on cytosolic free Ca2+ concentrations ([Ca2+]i) and phosphatidylinositol (PI) response were studied in cultured rat aortic vascular smooth muscle cells (VSMC). Binding of 125I-labeled-pET to rat VSMC was time- and temperature-dependent and the cell-bound 125I-labeled-pET was resistant to dissociate. Scatchard analysis of binding studies indicated the presence of a single class of high-affinity binding sites: the apparent Kd was 2-4 X 10(-10) M and the maximal binding capacity was 11,000-13,000 sites/cell. The binding was highly specific for pET because neither well-recognized vasoconstrictors, peptide neurotoxins, nor Ca2+-channel blockers affected the binding. pET dose-dependently (10(-9)-10(-7) M) induced a transient and sustained increase in [Ca2+]i in fura-2-loaded cells of which effect was largely dependent on extracellular Ca2+, whereas it had no significant effect on PI response in 3H-myoinositol-prelabeled cells. The present data clearly demonstrates the presence of specific receptors for pET distinct from those of the well-recognized vasoconstrictors and voltage-dependent Ca2+-channels in cultured rat VSMC, and suggest that pET-induced increase in [Ca2+]i is involved in the mechanism of its vasoconstriction.
The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on serotonin-induced inositol phosphate (IP) accumulation and intracellular free Ca2+ concentrations [( Ca2+]i) was investigated in cultured rat vascular smooth muscle cells. Pretreatment with TPA had no effect on basal levels of both IP production and [Ca2+]i, whereas it significantly attenuated serotonin-induced increases in both IP production and [Ca2+]i. These data suggest that protein kinase C is involved in the negative feedback control of serotonin-induced rises in both IP production and [Ca2+]i.
Using fura-2-loaded rat vascular smooth muscle cells (VSMCs) in culture, we have attempted to partially purify and characterize yet unidentified factor(s) from normal human plasma that stimulates cytoplasmic free Ca2+ concentration ([Ca2+]i). The plasma extract caused an immediate and transient increase of [Ca2+]i in a dose-dependent manner, of which effect was not prevented by pretreatment with either any of receptor antagonists for -adrenergic agonist, angiotensin II, arginine vasopressin, serotonin, thromboxane A2, or with EGTA and nifedipine. This novel plasma factor(s) was heat-stable and completely inactivated by pronase E, suggesting its protein nature. Furthermore, plasma extracts dose-dependently stimulated the accumulation of [3H] inositol phosphates in rat VSMCs. Sephadex G-50 gel chromatography of plasma extracts resolved one major component (mol wt 13,000) and two minor components with larger (greater than 30,000) and smaller (3,000) mol wt. Present study demonstrates the presence of hitherto unidentified plasma factor(s) with size heterogeneity capable of stimulating both mobilization of [Ca2+]i and breakdown of phosphatidylinositol-4,5-biphosphates in rat VSMCs.
Using 125I-labeled-Tyr0-rat(r)-calcitonin gene-related peptide (CGRP), a potent vasodilatory neuropeptide, we have identified and characterized specific binding sites for CGRP in cultured rat vascular smooth muscle cells (VSMC) and bovine endothelial cells (EC). rCGRP and human (h) CGRP equipotently inhibited 125I-rCGRP binding to both cells, but human calcitonin (hCT) was less potent and other unrelated polypeptides were ineffective. Both rCGRP and hCGRP, but not hCT, equally stimulated intracellular cAMP generation in both cells distinct from beta-adrenergic receptor-mediated mechanism, although they had no effect on cGMP generation in either cell or synthesis of prostacyclin in EC. Autoradiograph of affinity-labeled cell membranes revealed that 125I-rCGRP interacts with a single binding component of almost identical molecular size (approximately 60-kDa) in both cells under reducing and nonreducing conditions. The present study demonstrates for the first time the presence of CGRP receptors in cultured VSMC and EC, functionally coupled to adenylate cyclase system distinct from beta-adrenergic receptors. It is suggested that CGRP-induced vasorelaxation may be mediated partly by cAMP-dependent and/or endothelium-dependent mechanism.
The effects of H-7 and ML-9, inhibitors of protein kinase C and myosin light-chain kinase, respectively, on DNA synthesis stimulated by platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) were studied in cultured rat vascular smooth muscle cells (VSMC). H-7 and ML-9 significantly inhibited PDGF-stimulated DNA synthesis in lower concentrations, while both compounds were only effective in inhibiting EGF-induced DNA synthesis in higher concentrations. These data suggest that protein kinase C and myosin light-chain kinase activated by PDGF play a more important role in cell proliferation of VSMC than EGF.
The secretory mechanism of rat atrial natriuretic peptide (rANP) was studied in vitro with the use of primary culture of atrial myocytes from neonatal rats. Norepinephrine, phenylephrine, and carbamylcholine stimulated immunoreactive (IR) rANP secretion, whereas neither angiotensin II, arginine vasopressin, nor isoproterenol affected its secretion. The stimulatory effects of carbamylcholine and phenylephrine were blocked by atropine and prazosin, respectively. 12-O-tetradecanoylphorbol-beta-acetate (TPA), protein kinase C activator, induced a dose-dependent increase in IR rANP secretion, and TPA combined with Ca2+ ionophore ionomycin produced a synergistic effect. Ca2+-channel agonist BAY K 8644 also stimulated IR rANP secretion, the effect of which was blocked by Ca2+-channel antagonist nifedipine. These data suggest that alpha 1-adrenergic and muscarinic cholinergic agonists have direct action on rat cardiocytes to stimulate ANP secretion that involves receptor-mediated mobilization of intracellular Ca2+ and activation of protein kinase C.