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Biomedical subjects

T Ishimitsu

Publications and source records attributed to T Ishimitsu.

At least 127 records · Page 7Linked to original sources
PubMed1988

Enhanced generation of vascular thromboxane A2 in spontaneously hypertensive rats and its role in the rapid proliferation of vascular smooth muscle cells.

We examined vascular thromboxane A2 (TXA2) generation and its relation to a proliferation of vascular smooth muscle cells (VSMCs) in spontaneously hypertensive rats (SHRs). Aortic TXA2 release was significantly enhanced in 5-week-old SHRs, as compared with Wistar-Kyoto strain rats (WKY). The cultured VSMCs of SHRs exhibited a shorter doubling time and a greater [3H]thymidine uptake than those of WKY rats. OKY 046 a thromboxane synthetase inhibitor, tempered proliferation of VSMCs in SHRs, but not in WKY rats. STA2, a stable analog of TXA2, stimulated VSMC growth in WKY rats more than in SHRs. It is indicated that vascular TXA2 generation is enhanced, and partially participates in the rapid proliferation of VSMCs in SHRs.

Animals↗
PubMed1988

Alterations to the vascular vasodepressor prostaglandin system in DOCA-salt hypertensive rats and their enzymatic analysis.

To define the roles of vascular prostacyclin (PGI2) synthase for PGI2 generation in deoxycorticosterone acetate (DOCA)-salt hypertension, we investigated PGI2 synthase, phospholipase A2 and phospholipase C activities in the aortic wall of DOCA-salt prehypertensive and established hypertensive rats. Vascular PGI2 generation in the DOCA-salt hypertensive rats was increased by 91%, and was associated with an 88% increase in PGI2 synthase activity and lowered phospholipase C and A2 activity. In the prehypertensive stage, DOCA-salt rats showed reduced vascular PGI2 generation. Prostacyclin synthase activity was equal to that of controls. These data clearly suggest that DOCA-salt hypertensive rats increase their vascular PGI2 generation when they develop hypertension, and that this may be due to the activation of vascular PGI2 synthase.

Animals↗
PubMed1988

Enhanced phospholipase C activity in the vascular wall of spontaneously hypertensive rats.

To explore the roles of vascular phospholipase C activity in the development of hypertension, phospholipase C activity was examined in the aortic wall of spontaneously hypertensive rats (SHR). Phospholipase C activity was significantly enhanced (+87%, p less than 0.005) in 14-week-old SHR as compared with normotensive Wistar-Kyoto rats (WKY). The enzymatic activities were positively correlated with the levels of blood pressure in both of the rat strains (r = 0.62, p less than 0.003). Vascular phospholipase C was also significantly activated (+62%; p less than 0.006) in the aortic wall of 4-week-old prehypertensive SHR, as compared with age-matched WKY. In contrast, vascular phospholipase A2 activity was unaffected in the aortic wall of either adult or very young SHR. There was no difference in the cardiac phospholipase C activity between adult SHR and WKY. The vascular phospholipase C of SHR had a lower Michaelis constant (Km) value than that of WKY. Moreover, its pH profile and calcium requirement differed in part from those of WKY. These results indicate that the activation of vascular phospholipase C precedes the development of hypertension and that the enhancement may be induced by both quantitative and qualitative changes in phospholipase C in SHR.

Animals↗
PubMed1988

Thromboxane and vascular smooth muscle cell growth in genetically hypertensive rats.

The vascular wall has the capacity to produce thromboxane A2. However, the role of vascular thromboxane A2 is still uncertain. In this study, we examined the relationship between vascular thromboxane A2 generation and vascular smooth muscle cell growth in spontaneously hypertensive rats (SHR). Vascular thromboxane A2 generation was significantly enhanced by 49% in 5-week-old and by 117% in 15-week-old SHR as compared with age-matched Wistar-Kyoto rats (WKY). Thromboxane A2 generation was also significantly enhanced by 59% in the cultured vascular smooth muscle cells of SHR when compared with production in WKY. Vascular smooth muscle cells of SHR exhibited a significantly shortened doubling time (by 32%) and greater [3H]thymidine uptake (by 56%), as compared with those of WKY. OKY 046 (10(-5) M), a thromboxane synthase inhibitor, significantly tempered the rapid vascular smooth muscle cell growth in SHR by 9% for doubling time and by 10% for [3H]thymidine uptake. OKY 046 did not influence the doubling time of WKY. Conversely, a stable analogue of thromboxane A2 dose-dependently stimulated the [3H]thymidine uptake by vascular smooth muscle cells of WKY, and, at a concentration of 10(-5) M, shortened the doubling time of vascular smooth muscle cells of WKY by 11%, whereas it showed slight effects on SHR. These data indicate that vascular thromboxane A2 is involved in the regulatory mechanism of vascular smooth muscle cell growth and that enhanced vascular thromboxane A2 generation is partly responsible for the rapid proliferation of vascular smooth muscle cells of SHR. The alterations of vascular thromboxane production may be a key trait for genetic hypertension.

Animals↗
PubMed1988

Tricuspid regurgitation diagnosed by intravenous digital subtraction angiography.

In spite of numerous available diagnostic methods, controversies concerning the precise diagnosis of tricuspid regurgitation (TR) still remain. In right ventriculography, catheter placement may modify tricuspid valvular function. Though noninvasive Doppler echocardiography is a useful method, it is sometimes too sensitive for clinical use. Furthermore, it is not applicable to cases in which ultrasound penetration is limited. In this study, we evaluated TR using intravenous digital subtraction angiography (DSA), which can provide good images even in cases with poorly recorded echocardiograms. For this study, we placed a catheter in the superior vena cava. Cardiac DSA examinations were performed in one hundred and one patients with heart disease. We injected 35 ml of contrast medium at a speed of 18 ml/sec via a catheter introduced in the superior vena cava. DSA images by continuous mode were obtained in the RAO projection for 15-20 sec. Sequential DSA images were observed and analyzed by time-density curves of the regions of interest (ROI) which were placed in the right ventricle (RV) and inferior vena cava (IVC). Doppler echocardiography was performed for 16 cases in which TR was suspected. Of these, phonocardiography with jugular pulse tracing was recorded for 14 and contrast echocardiography were performed for six, respectively. In cases without evidence of TR, regurgitation of contrast medium into the IVC during RV systole was not recorded by the DSA method. In cases of clinically-proven TR, regurgitation into the IVC during RV systole was observed. Thus, this was considered a diagnostic feature of positive TR using the DSA method, and 13 of the 16 cases undergoing Doppler echocardiography were diagnosed as having TR using the DSA method. The severity of TR was categorized as mild, moderate and severe according to analyses of time-density curves. The severity established by the DSA method showed a close correlation with the clinical severity of TR. Doppler echocardiography was negative for TR in two of the 13 cases, but positive for TR in two of the 16 suspected cases only by the Doppler method. In cases of moderate to severe TR diagnosed by the DSA method, jugular pulse tracings showed a regurgitant wave. By contrast echocardiography, TR was evident only in cases of severe TR diagnosed by the DSA method. In conclusion, the DSA method proved useful for diagnosing TR.

Adult↗
PubMed1988

[Type IV Ehlers-Danlos syndrome associated with mitral valve prolapse: a case report].

A 52-year-old male patient with the Ehlers-Danlos syndrome (familial hypermobility of the joints, hyperextensibility of the skin and atrophic cutaneous scars) was evaluated because of a mitral regurgitant murmur. Echocardiography demonstrated marked mitral valve prolapse of the both leaflets and vegetation-like thickening of the anterior leaflet of the mitral valve. Two-dimensional color flow mapping showed severe mitral regurgitation. This patient had also acrogeria-like facial appearance and very thin skin (subcutaneous veins were readily visible). He developed repeated rupture of radial, ulnar and middle cerebral arteries and expired. A histological section of the ruptured ulnar artery demonstrated no infectious process. In view of the joint hyperextensibility, very thin skin, characteristic facial appearance and the spontaneous occurrence of three successive ruptures of peripheral arteries, a diagnosis of Ehlers-Danlos syndrome (type IV) was made. Although mitral valve prolapse is reportedly common in type I, II and III Ehlers-Danlos syndrome, this report emphasizes that it may also occur in patients with type IV Ehlers-Danlos syndrome and the relevant literatures are reviewed.

Echocardiography↗
PubMed1987

Aneurysm of patent ductus arteriosus in an adult case: findings of cardiac catheterization, angiography, and pathology.

A 42-year-old male was admitted to our hospital for evaluation of a left precordial continuous murmur. Results of catheterization revealed a step-up of oxygen content in the pulmonary arteries and the calculated left-to-right shunt flow was 40% of the pulmonary arterial flow. Furthermore, aortography unexpectedly revealed an aneurysm of the patent ductus arteriosus. During surgery, the aneurysm was discovered to arise from the frontal wall of the ductus arteriosus, and histological observation showed focal necrosis and mucoid degeneration of the media of the aneurysmal wall in contrast to a thickened intimal fibroelastosis of the adjacent ductal wall. This is presumed to be the first adult case of patent ductal aneurysm ever reported in which antemortem diagnosis and surgical treatment were successfully conducted. Our case may suggest that the fragility of the ductal wall following the structural change in an incomplete closing process is considered as a potential pathogenesis of ductal aneurysm formation.

Adult↗
PubMed1987

Prostacyclin synthase and phospholipases in the vascular wall of experimental hypertensive rats.

To reveal the role of enzymes involved in PGI2 synthesis for vascular PGI2 generation in experimental hypertensive models, we defined PGI2 synthase and phospholipases activities in the aortic wall of two different experimental hypertensive rats, e.g. spontaneously hypertensive rats (SHR) and desoxycorticosterone acetate (DOCA)-salt hypertensive rats. In the stage of established hypertension both of the hypertensive models had a significantly large capacity of the vascular wall to produce PGI2, as compared to respective control rats. PGI2 synthase activities in the vascular wall were significantly increased by 27% for SHR and by 80% for DOCA-salt hypertensive rats. Moreover, the enzymatic activities were closely related to the blood pressure values for both of the models. On the other hand, phospholipase C or phospholipase A2 activities were increased or unchanged in SHR, respectively, whereas both of the phospholipases were significantly decreased in DOCA-salt hypertensive rats. Thus, it is indicated that PGI2 synthase is partly responsible for the increased PGI2 generation in the vascular wall of SHR and DOCA-salt hypertensive rats, and that vascular phospholipase C is playing a more important role in providing arachidonate for PGI2 synthesis in SHR.

Animals↗
PubMed1987

Relationship between the renin-aldosterone system and atrial natriuretic polypeptide in rats.

In order to examine the relationship between the renin-aldosterone system and atrial natriuretic polypeptide (ANP), we investigated the effects of alpha-human atrial natriuretic polypeptide (alpha-hANP) on the plasma concentrations of renin (PRC) and aldosterone (PAC), as well as the effects of captopril pretreatment on the natriuresis and blood pressure reduction induced by alpha-hANP in rats. Although alpha-hANP infused into conscious rats at 0.67 microgram min-1 kg-1 markedly increased the urinary excretion of sodium and decreased mean arterial pressure, its infusion did not change PRC; however, it significantly lowered PAC. Frusemide infusion at 20.8 micrograms min-1 kg-1 induced natriuresis comparable with that of alpha-hANP and it elevated both PRC and PAC, but mean arterial pressure was not altered. Pretreatment of rats with captopril did not have any significant influence on the acute natriuretic and hypotensive effects of alpha-hANP. Although the inhibitory effect of ANP on the renin-aldosterone system may be involved in the chronic modulation of body fluid volume and blood pressure, this effect does not seem to be directly involved in the acute natriuretic and hypotensive effects of the peptide.

Aldosterone↗
PubMed1987

Salt-induced plasma factor that inhibits platelet thromboxane A2 release and renal prostaglandin E2 production in rats.

This study examined the relationship between a plasma factor (or factors) that inhibits the release of thromboxane A2 from platelets and excessive salt intake in rats. The plasma factor, termed platelet inhibitory factor, was also characterized. The release of thromboxane A2 from thrombin-activated platelets was reduced in Wistar rats that were uninephrectomized and given 2% saline for a week, but not in rats with acute volume expansion. Platelet inhibitory factor was extracted from the plasma of these uninephrectomized and saline-loaded rats and partially purified using membrane sieves, reverse-phase high performance liquid chromatography (HPLC), modified straight-phase HPLC, and gel-permeation column chromatography. The molecular weight of the factor was about 4300 daltons by gel filtration method. The partially purified platelet inhibitory factor decreased the release not only of thromboxane A2, but also of prostaglandin E2 and prostaglandin D2 from thrombin-activated platelets. The factor inhibited the aggregation of human platelets induced by adenosine 5'-diphosphate (ADP), collagen, and thrombin, but not that by arachidonate. The platelet inhibitory factor reduced the activities of phospholipases A2 and C but did not affect the conversion of arachidonate to thromboxane A2. Furthermore, platelet inhibitory factor decreased prostaglandin E2 production in cultured renal cells, and platelet inhibitory factor-like activity was detected in kidney extract from the salt-loaded rats. These results suggest that platelet inhibitory factor is produced by chronic salt intake and involved in the functional alterations of the platelets and probably the kidneys, mainly through its inhibitory action on the liberation of arachidonate.

Animals↗
PubMed1986

Blood pressure, renal and endocrine responses to alpha-human atrial natriuretic polypeptide in healthy volunteers.

Intravenous infusion of graded doses of alpha-human atrial natriuretic polypeptide (alpha-hANP) resulted in a dose-dependent decrease in blood pressure and an increase in heart rate in 11 healthy male volunteers. However, there were no significant changes in urine output or in the urinary excretion rate of sodium. Glomerular filtration rate did not change, while renal blood flow decreased, leading to significant increases in filtration fraction and renal vascular resistance. Although plasma renin activity (PRA) and plasma concentration of norepinephrine (PNE) increased during infusion of alpha-hANP (both p less than 0.001), plasma concentrations of aldosterone (PA) and cortisol (PC) decreased (both p less than 0.001). Plasma concentration of arginine vasopressin (PAVP) did not change during the infusion, but greatly increased after cessation of the infusion. The hematocrit increased slightly, but significantly, during the infusion. These results show that, although alpha-hANP has a potent hypotensive action and inhibits the secretion of aldosterone, cortisol, and probably arginine vasopressin, it does not dilate renal vessels in normotensive persons, and likely increases vascular permeability. The lack of consistent diuretic and natriuretic responses to alpha-hANP may be related to the predominance of the hypotensive effect over the renal effects of the peptide in normotensive persons, or a diurnal change may have served to obscure such a response.

Adult↗
PubMed1985

Determination of m- and p-O-methylated products of L-3,4-dihydroxyphenylalanine using high-performance liquid chromatography and electrochemical detection.

In a study of in vitro and in vivo metabolism of L-3,4-dihydroxyphenylalanine (L-Dopa), two methods of high-performance liquid chromatography (HPLC) were used to separate the m- and p-O-methylated products. A reversed-phase column and an aqueous mobile phase by gradient elution were used; the elute was analyzed electrochemically with a single amperometric and dual coulometric electrode. The L-Dopa and its O-methylated products could be detected individually in the enzymatic methylation of rat liver homogenate and in patients with Parkinson's disease. Meta/para ratios of O-methylation are easily obtained by this method.

Animals↗
PubMed1985

Simultaneous assay of 3,4-dihydroxyphenylalanine, catecholamines and O-methylated metabolites in human plasma using high-performance liquid chromatography.

We devised a procedure for the simultaneous determination of 3,4-dihydroxyphenylalanine, catecholamines and O-methylated metabolites using a reversed-phase liquid chromatographic system. Detection is achieved by an electrochemical detector and a fluorescence detector connected in series. Sample preparation is kept to a minimum, and involves precipitation of proteins with trichloroacetic acid and perchloric acid, and subsequent neutralization, thus omitting the commonly adopted adsorption step. Chromatographic peaks were identified on the basis of retention behaviour and the ratio of responses at several oxidation potentials. The method was applied to the quantitative determination of 3,4-dihydroxyphenylalanine, catecholamines and O-methylated metabolites in human plasma.

Catecholamines↗
PubMed1985

Origin of the third heart sound: comparison of ventricular wall dynamics in hyperdynamic and hypodynamic types.

To investigate the left ventricular wall dynamics conducive to the third heart sound (S3) in both hyper- and hypodynamic filling conditions, eight dogs were studied in which an S3 was produced by hypoxemia and in eight others by acute mitral regurgitation. Pulse transit sonomicrometry crystals were used to measure external left ventricular dimension dynamics in the two principal axes. A miniature accelerometer was used to detect the epicardial S3 vibration. The development of the S3 was invariably associated with an increased peak velocity of long-axis external dimensional expansion in early diastole. This enhanced long-axis filling activity was not dependent on increased global chamber or short-axis filling dynamics and sometimes occurred when global filling rate was unchanged. In addition, the short-axis filling rate was sometimes reduced as the S3 developed. It is concluded that the common denominator of S3 generation in this acute dog model is exaggerated long-axis diastolic expansion activity which is present in both hyper- and hypodynamic left ventricular filling.

Acute Disease↗
PubMed1985

Hepatocellular carcinoma detected by iodized oil.

This study assesses the diagnostic value of Lipiodol (iodized oil) and computed tomography (CT) in detecting hepatocellular carcinoma (HCC). Twenty-four patients who were suspected of having HCC received injections of a small amount of Lipiodol, along with an antitumor agent, in the hepatic artery following routine celiac angiography. CT scans obtained 7-10 days after Lipiodol administration demonstrated HCC in distinct contrast to the surrounding noncancerous parenchyma. In particular, the CT-Lipiodol procedure disclosed many small HCC lesions that were not shown by celiac angiography, scintigraphy, CT with and without contrast medium enhancement, and ultrasonography. Although this procedure may miss very small or highly fibrotic lesions, it is recommended for patients suspected of having HCC and for patients for whom hepatic resection is being considered.

Adult↗