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Biomedical subjects

M Naruse

Publications and source records attributed to M Naruse.

At least 73 records · Page 4Linked to original sources
PubMed1998

Tetramethylpyrazine, a Chinese drug, blocks coronary vasoconstriction by endothelin-1 and decreases plasma endothelin-1 levels in experimental animals.

The purpose of this study was to investigate effects of tetramethylpyrazine (TMP), a Chinese plant-derived medicine, on coronary vasoconstriction and related electrocardiographic and histologic changes caused by endothelin-1 (ET-1), and on plasma ET-1 levels. ET-1 (75 pmol) was administered into the left coronary artery (LCA) in anesthetized closed-chest dogs with and without prior infusion of TMP (80 mg/kg). Coronary arterial diameter (CAD) was determined by coronary arteriography (CAG). Blood pressure and electrocardiogram (ECG) were monitored continuously. Histologic damage in tissues was ascertained microscopically. Plasma ET-1 and 6-keto-PGF1 levels were determined by RIA 90 min after i.v. injection of TMP (25 mg/kg; n = 5) in rabbits. Intracoronary injection of ET-1 resulted in a significant vasoconstriction of the entire vascular bed of the LCA, with a decrease in CAD of 35.9 +/- 5.7% (n = 5; p < 0.01) and ischemic changes on ECG and in tissues of endocardium, myocardium, coronary endothelial cells, and capillary vessels. Pretreatment with TMP produced a significant increase in CAD by 38.5 +/- 7.8% (n = 5; p < 0.01) and greatly suppressed the vasoconstriction produced by ET-1. The myocardial tissue damage estimated from the ratio of ischemic area for the entire area after ET-1 injection (35.6%) was completely abolished by TMP (0.6%). In addition, TMP injection induced a significant decrease in plasma ET-1 levels and an increase in 6-keto-PGF1 levels in rabbits. The Chinese medicine TMP could be a useful therapeutic agent in ischemic heart disease by suppressing coronary vasoconstriction and ischemic changes in the tissues produced by ET-1.

6-Ketoprostaglandin F1 alpha↗
PubMed1998

Immunoreactive endothelin levels in the vitreous fluid are decreased in diabetic patients with proliferative retinopathy.

Endothelin (ET) plays an important role in the pathogenesis of various cardiovascular lesions. To elucidate the pathophysiologic significance of ET in the development of diabetic retinopathy, we determined immunoreactive ET levels in the vitreous fluid collected during vitrectomy in seven patients with non-insulin dependent diabetes mellitus with proliferative diabetic retinopathy and in 10 nondiabetic subjects as controls. Immunoreactive vitreous ET levels in diabetic patients with proliferative retinopathy (7.5 +/- 3.4 pg/ml, mean +/- SD) were significantly lower than those in the nondiabetic subjects (55.0 +/- 38.1 pg/ml; p < 0.005). The decreased rather than increased immunoreactive ET levels may simply reflect severe endothelial injury to the retinal vessels caused by diabetic microangiopathy rather than an important role in diabetic retinopathy.

Blood Pressure↗
PubMed1998

Gene expression of endothelin-1 and endothelial-type nitric oxide synthase in cardiovascular tissues of stroke-prone spontaneously hypertensive rats/Izm: effects of the angiotensin-converting enzyme inhibitor aracepril.

We studied target organ-protective effects of aracepril, an angiotensin-converting enzyme inhibitor, and the expression of endothelin-1 (ET-1) and nitric oxide synthase (NOS) mRNA. Aracepril (30 mg/kg) was administered orally to Izumo strain of stroke-prone spontaneously hypertensive rats (SHR-SP/Izm) for 8 weeks from 4 weeks of age and for 4 weeks from 8 weeks of age. The expression of ET-1 and endothelial NOS (eNOS) mRNA in the heart, aorta, kidneys, and brain cortex, and the expression of neuronal NOS (bNOS) mRNA in brain cortex, were analyzed by RT-PCR/Southern blotting or RNase protection analysis. Administration of aracepril markedly lowered blood pressure and decreased left ventricular weight in SHR-SP/Izm. Expression of ET-1 mRNA in the heart, kidneys, and brain was significantly enhanced in SHR/SP/Izm compared with that in WKY/Izm. Aracepril significantly decreased the expression of ET-1 mRNA, whereas there was no significant change of that in the aorta. Although expression of eNOS mRNA in the heart, aorta, and kidneys did not show any significant difference between the two strains of rats, administration of aracepril for 8 weeks significantly decreased the expression of eNOS and bNOS mRNA in brain tissue. These results suggested that aracepril may protect major target organs by modifying the expression of ET-1 and NOS mRNA, in addition to its hypotensive effect.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Effects of tetramethylpyrazine, a Chinese medicine, on plasma endothelin-1 levels during acute pulmonary hypoxia in anesthetized dogs.

Our study was designed to elucidate the effects of tetramethylpyrazine (TMP), a Chinese medicine, on plasma endothelin-1 (ET-1) levels in dogs with acute pulmonary alveolar hypoxia. Anesthetized dogs were used under artificial ventilation with room air or a hypoxic gas mixture (10% O2 and 90% N2) (n = 10) for 60 min. Effects of TMP (80 mg/kg) were studied by i.v. injection of TMP before exposure to hypoxia (n = 8). Mean pulmonary arterial pressure (PAPm), systemic arterial pressure (SAPm), right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and heart rate (HR) were measured. The pulmonary vascular resistance (PVR) was calculated by the equation of (PAPm-PCWP) x 8/CO. Plasma ET-1 levels were determined in the abdominal aorta and pulmonary artery by RIA. The effects of TMP on PAP and plasma ET-1 level were evaluated by using percent increase in PAPm and the change of Da-pET (delta ET) before and after hypoxia. Both PAPm and PVR were significantly elevated 5 min after acute hypoxia over a period of 60 min, whereas CO and PCWP did not change. Plasma ET-1 levels in the abdominal aorta and Da-pET showed a significant increase. Administration of TMP significantly decreased the hypoxia-induced increase in the PAPm, PVR, and delta ET. These results suggest that TMP could be a useful therapeutic agent in the treatment of pulmonary hypertension induced by acute hypoxia through decrease of plasma ET-1 levels.

Anesthesia, General↗
PubMed1998

Plasma concentration of brain natriuretic peptide as an indicator of cardiac ventricular function in patients on hemodialysis.

The plasma concentration of human brain natriuretic peptide (BNP) was measured by immunoradiometric assay in patients on maintenance hemodialysis (HD) to assess the possible relationship between the plasma levels of this peptide and cardiac ventricular function, as judged by M-mode echocardiography. The plasma BNP levels in the pre-HD state were significantly higher (688.5 +/- 154.5 pg/ml) than those of healthy subjects (<40 pg/ml). In addition, the plasma BNP levels were slightly decreased during HD (post-HD, 617.3 +/- 157.1 pg/ml). There was no correlation between the plasma levels of BNP and body weight changes during HD. The mean plasma BNP level was significantly higher in the group of patients with a low left ventricular ejection fraction (EF < 60%) than in the group with a normal EF. In the patients as a whole, there was an inverse correlation between plasma BNP levels and EF. Moreover, a positive correlation was found between plasma BNP levels and left ventricular mass index (r = 0.57, p < 0.05). These results suggest that plasma BNP levels increase in response to chronic stimulation in accordance with increased cardiac load, and that they may be a possible indicator of reduced ventricular function in HD patients.

Atrial Natriuretic Factor↗
PubMed1998

Potentiation of natriuretic peptide action by the beta-adrenergic blocker carvedilol in hypertensive rats: a new antihypertensive mechanism.

Treatment with a beta-adrenergic blocker (beta-blocker) in hypertension is associated with increased plasma atrial natriuretic peptide (ANP) levels despite a decrease in cardiac overload. The mechanism and pathophysiological significance of the phenomenon remain unclear. To clarify the role of the ANP system in the antihypertensive effects of the beta-blocker, we investigated the effects of carvedilol (30 mg/kg x day, orally, for 4 weeks) on the ANP system in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm). Plasma ANP levels showed a significant increase despite a significant decrease in blood pressure and heart rate in the carvedilol group. Although ANP messenger RNA levels in the heart did not change, messenger RNA levels of the natriuretic peptide-C (NP-C) receptor as a clearance receptor showed a significant decrease in both the aorta and lung in the carvedilol group. NP-C receptor densities were also significantly decreased in the lung in this group. The biological half-life of exogenous ANP in circulating blood was prolonged in the carvedilol group compared with that in the control group. Administration of the ANP receptor antagonist, HS-142-1, resulted in a greater increase in systolic blood pressure in the carvedilol group than in the control group. In addition, both basal and ANP-stimulated cGMP contents in the aorta were significantly higher in the carvedilol group. These results suggest that carvedilol potentiates the hypotensive action of ANP by increasing plasma ANP levels and enhancing the vascular response to ANP. These effects were closely related to the down-regulation of the NP-C receptor. The newly found mechanism seems to account for a sizable portion of the antihypertensive effects of carvedilol and could be of potential importance in the treatment of cardiovascular disease with beta-blockers.

Adrenergic beta-Antagonists↗
PubMed1998

[Pathophysiological significance of the natriuretic peptide system: receptor subtype as another key factor].

The natriuretic peptide (NP) system is one of the most important systems regulating blood pressure and body-fluid homeostasis. The biological activities of the system are determined by the NPs and the receptors, which are comprised of three subtypes: NP-AR and NP-BR related to biological activities and NP-CR related to the clearance of NP. We focused our studies on the receptor subtypes. In hypertensive rats (SHR-SP/Izm, DOCA/salt), NP-AR was upregulated and NP-CR was downregulated. The ACE inhibitor derapril, but not the Ca2+ blocker manidipine, normalized the upregulated NP-AR, but the effect was completely abolished by the bradykinin beta 2-receptor antagonist, suggesting that bradykinin regulates the vascular NP-AR. The AT1 antagonist TCV-116, but not manidipine, reversed the downregulated NP-CR. Ang II decreased NP-CR in cultured aortic smooth muscle cells. These results suggest that upregulation of NP-AR and downregulation of NP-CR with the increased plasma NPs counteract hypertension by enhancing the action of NP. A beta-blocker (carvedilol) potentiated the hypotensive action of NPs by increasing plasma NPs and enhancing the vascular response to NPs via downregulation of the vascular and lung NP-CR. The newly found mode of actions could be related to its anti-heart failure effect. In genetically hyperglycemic Wistar fatty rats, vascular NP-BR and NP-AR were upregulated. Since plasma ANP and vascular CNP were significantly increased, the local CNP/NP-BR system as well as the systemic ANP/NP-AR system may play an important role in counteracting vascular remodeling in diabetes mellitus. All these observations provide in vivo evidence for the pathophysiological significance of the receptor subtype of the NPs.

Animals↗
PubMed1998

The relatively high frequency of p53 gene mutations in multiple and malignant phaeochromocytomas.

To explore the clinical significance of p53 in the pathogenesis of adrenal neoplasms, we investigated the incidence of p53 gene mutations in functioning human adrenal tumours using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique to screen p53 exons 4 to 9. We examined 29 adrenocortical adenomas (primary aldosteronism, n=17; Cushing's syndrome, n=12, all benign), and 33 phaeochromocytomas (benign solitary, n=18; benign multiple, n=5; malignant, n=10) in Japanese and Chinese patients. PCR-SSCP did not show any abnormal band-shifts in any of the adrenocortical adenoma and benign solitary phaeochromocytoma tissues. In contrast, six phaeochromocytoma tissues (two cases benign multiple, four cases malignant) showed PCR-SSCP band-shifts. Subsequent DNA sequencing analysis of the shifted bands revealed six cases with nine mutations or intronic sequence alterations: three cases contained sequence alterations within intronic regions, three cases with silent mutation (sequence alteration in codon without amino acid alteration), and three cases contained missense mutations (one case each in exons 5, 6 and 9). Immunohistochemical staining demonstrated that two of three cases with missense mutations and one case with an intronic sequence alteration over-expressed p53 protein in tumour cell nuclei. We observed no association between p53 gene mutation and p21/WAF1/Cip-1 expression. The relatively high incidence of p53 gene mutations or intronic sequence alteration in multiple and malignant phaeochromocytomas, but not in benign solitary cases, suggests that p53 mutation could play some role in the pathogenesis of multiple and/or malignant phaeochromocytomas.

Adenoma↗
PubMed1998

Long-term regulation of inner medullary collecting duct urea transport in rat.

Facilitated urea transport is regulated acutely by arginine vasopressin (AVP) and hyperosmolality in rat terminal inner medullary collecting duct (IMCD). This study tested whether chronic diuresis or antidiuresis regulates facilitated urea transport. Basal and AVP-stimulated urea permeabilities (Purea) were measured in perfused IMCD subsegments. Rats were made: (1) diuretic by giving them sugar water (with or without food) or furosemide; or (2) antidiuretic by water deprivation. They were then compared with untreated rats given food and water ad libitum. Terminal IMCD from untreated rats had a high basal Purea that was significantly increased by AVP. Diuresis significantly increased basal Purea in terminal IMCD in all five diuresis protocols. Water deprivation for 1 or 3 d had no effect on basal or AVP-stimulated Purea in the IMCD2 subsegment of the terminal IMCD. In contrast, 3 d of water deprivation significantly increased both basal and AVP-stimulated Purea in the IMCD3 subsegment; 1 d of water deprivation had no effect on basal or AVP-stimulated Purea. Next, initial IMCD (IMCD1) were studied. Initial IMCD from untreated rats had a low basal Purea that was not increased by AVP (10 nM). Water diuresis (with or without food) for 3 to 5 d had no effect on basal Purea but significantly increased AVP-stimulated Purea. Furosemide diuresis and water diuresis for 1 or 7 d had no effect on either basal or AVP-stimulated Purea in initial IMCD. Water deprivation for 2 to 3 d, but not for 1 d, significantly increased basal Purea in initial IMCD, whereas water deprivation for 1 d increased AVP-stimulated Purea. It is concluded that chronic changes in hydration cause heterogeneous changes in facilitated urea transport in rat IMCD subsegments.

Animal Feed↗
PubMed1998

Cardiac malignant pheochromocytoma with bone metastases.

A patient with malignant cardiac pheochromocytoma with bone metastases is described. The primary tumor was located between the pulmonary trunk and the left atrium, while metastatic lesions were found in the iliac bones. Treatments with antihypertensive agents, alpha-methylparatyrosine, and combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine partially improved the patient's symptoms, catecholamine levels, and the metastatic lesion of the iliac bones. However, the primary tumor in the heart progressively increased in size and the patient died of disseminated intravascular coagulation and other various complications about 4 years after the diagnosis of the disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Roles of heme oxygenase/carbon monoxide system in genetically hypertensive rats.

Although carbon monoxide (CO) has been suggested to be involved in the regulation of cardiovascular function through activation of soluble guanylyl cyclase, the pathophysiological significance in hypertension remains unknown. We therefore examined the effects of heme oxygenase (HO) inhibitor zinc protoporphyrin IX (ZnPP-IX) on blood pressure and determined HO mRNA expression level in various tissues in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm) and Wistar Kyoto rats (WKY/Izm). Although ZnPP-IX significantly increased systolic blood pressure in both strains, the increment of blood pressure was larger in SHR-SP/Izm than in WKY/Izm. An essentially similar increase of blood pressure was demonstrated even in the ganglion blocker-pretreated rats. Constitutive type HO-2 mRNA levels in the aorta and kidney and inducible type HO-1 mRNA levels in the cardiac ventricle were significantly increased in SHR-SP/Izm compared with WKY/Izm. Clearly these results indicate the importance of the endogenous HO/CO system in the peripheral tissues in genetically hypertensive rats.

Animals↗
PubMed1997

Interrelation between nitric oxide synthase and heme oxygenase in rat endothelial cells.

The gene expression and interrelation of the constitutive type nitric oxide (NO) synthase-III as a NO-forming enzyme and heme oxygenase-2 as a carbon monoxide-forming enzyme were studied in cultured rat aortic endothelial cells. Both NO synthase-III and heme oxygenase-2 mRNAs were demonstrated in the endothelial cells by RNAase protection analysis. NO synthase-III mRNA was upregulated in the presence of the heme oxygenase inhibitor, zinc protoporphyrin IX, but not in the presence of the NO synthase inhibitor, N(G)-nitro-L-arginine. Although heme oxygenase-2 mRNA was significantly upregulated in the presence of both NO synthase inhibitor and heme oxygenase inhibitor, the increase was greater with the NO synthase inhibitor. These results provide the first evidence for the concomitant gene expression of NO synthase-III and heme oxygenase-2, and their compensatory interrelation in endothelial cells.

Animals↗
PubMed1997

Apical extracellular calcium/polyvalent cation-sensing receptor regulates vasopressin-elicited water permeability in rat kidney inner medullary collecting duct.

During antidiuresis, increases in vasopressin (AVP)-elicited osmotic water permeability in the terminal inner medullary collecting duct (tIMCD) raise luminal calcium concentrations to levels (> or = 5 mM) above those associated with the formation of calcium-containing precipitates in the urine. Calcium/polycation receptor proteins (CaRs) enable cells in the parathyroid gland and kidney thick ascending limb of Henle to sense and respond to alterations in serum calcium. We now report the presence of an apical CaR in rat kidney tIMCD that specifically reduces AVP-elicited osmotic water permeability when luminal calcium rises. Purified tIMCD apical membrane endosomes contain both the AVP-elicited water channel, aquaporin 2, and a CaR. In addition, aquaporin 2-containing endosomes also possess stimulatory (G(alpha q)/G(alpha 11) and inhibitory (G(alpha i1, 2, and 3)) GTP binding proteins reported previously to interact with CaRs as well as two specific isoforms (delta and zeta) of protein kinase C. Immunocytochemistry using anti-CaR antiserum reveals the presence of CaR protein in both rat and human collecting ducts. Together, these data provide support for a unique tIMCD apical membrane signaling mechanism linking calcium and water metabolism. Abnormalities in this mechanism could potentially play a role in the pathogenesis of renal stone formation.

Animals↗
PubMed1997

Marked reduction of mouse peritoneal CD5+ B cells by intraperitoneal administration of lipopolysaccharide.

Intraperitoneal administration of lipopolysaccharide to mice induced a marked reduction of CD5+ B cells in the peritoneal cavity. The reduction was not induced by intravenous, subcutaneous, or oral administration of lipopolysaccharide. The reduction continued for about 10 days after the injection, and the CD5+ B-cell count recovered to the normal state about 14 days after the injection. The reduction of peritoneal CD5+ B cells might be caused by apoptotic cell death. Injection of lipopolysaccharide did not result in production of antibody to lipopolysaccharide. On the other hand, intraperitoneal injection of heat-killed bacteria did not induce a reduction of peritoneal CD5+ B cells and elicited the definite production of antibody to lipopolysaccharide.

Animals↗
PubMed1997

Antihypertensive and vasculo- and renoprotective effects of pioglitazone in genetically obese diabetic rats.

Although an improvement of insulin sensitivity has been shown to be a new therapeutic approach for treating diabetes mellitus, details of effects of this treatment on the cardiovascular system and possible renal complications remain unknown. In the present study, we investigated the effects of a thiazolidine derivative, pioglitazone, and examined the insulin-sensitizing action on blood pressure, nephropathy, and vascular changes in genetically obese diabetic Wistar fatty (WF) rats. Pioglitazone (3 mg.kg-1.day-1) was orally administered for 13 wk starting at the age of 5 wk, and the results were compared with those of vehicle-treated WF rats. At the age of 18 wk, vehicle-treated WF rats were associated with mild hypertension, nephropathy with proteinuria histological glomerular injury, and renal arteriolosclerosis in addition to hyperglycemia, hyperinsulinemia, and hyperlipidemia. Treatment with pioglitazone significantly improved glucose and lipid metabolism. In addition, it lowered blood pressure, decreased proteinuria, and prevented glomerular injury, renal arteriolosclerosis, and aortic medial wall thickening, whereas body weight, food intake, sodium balance, and urinary norepinephrine excretion were significantly increased. These results suggest that the insulin-sensitizing agent pioglitazone is effective in correcting not only glucose and lipid metabolism but also cardiovascular and renal complications in non-insulin-dependent diabetes mellitus.

Animals↗
PubMed1997

Gene expression of endothelial type isoform of nitric oxide synthase in various tissues of stroke-prone spontaneously hypertensive rats.

Nitric oxide (NO) has been suggested to play important roles in the pathophysiology of various cardiovascular diseases. This study tested the hypothesis that an attenuated biological action of NO in hypertension is attributed to a change in the gene expression of NO synthase (NOS), a key enzyme involved in NO formation. The expression level of mRNA of endothelial type NOS (NOS-III) was determined in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm) and Wistar Kyoto rats (WKY/Izm) by ribonuclease protection assay using a partial clone as probe. NOS-III mRNA was expressed ubiquitously in various tissues of WKY/Izm and SHR-SP/Izm either at 5 wk or 13 wk of age. There was no significant difference in the tissue expression of NOS-III mRNA between the two strains at either age. The intensity and localization of the hybridization signal for NOS-III mRNA in the heart of SHR-SP/Izm did not differ from those in the heart of WKY/Izm. These results suggest that the attenuated biological action of NO implied in genetically hypertensive rats is not attributed to an abnormality at the level of NOS-III mRNA expression in the tissues, although lack of an increase in NOS-III gene expression, despite the hypertensive hemodynamic stress, may modify the blood pressure in hypertension.

Animals↗
PubMed1997

Left ventricular hypertrophy is more prominent in patients with primary aldosteronism than in patients with other types of secondary hypertension.

We determined functional and morphological changes of the heart by 2-dimensional and pulse Doppler echocardiography in 20 patients with primary aldosteronism and compared the results with those in 50 healthy normotensive subjects, 12 patients with Cushing's syndrome, 9 patients with pheochromocytoma, and 47 patients with essential hypertension. All hypertensive groups had greater left ventricular mass indexes than did the normotensive group (76.9 +/- 17.2 g/m2). Despite similar age distribution, blood pressure during antihypertensive treatment, and duration of hypertension, the primary aldosteronism group had a significantly greater left ventricular mass index (152.5 +/- 42.5 g/m2) than did the Cushing's syndrome (103.4 +/- 37.5 g/m2), pheochromocytoma (122.4 +/- 28.5 g/m2), and essential hypertension (101.4 +/- 32.8 g/m2) groups. The left ventricular posterior wall thickness and interventricular septal wall thickness were significantly greater in the hypertensive groups than in the normotensive group and also significantly greater in the primary aldosteronism group than in any of the other hypertensive groups. By contrast, there were no significant differences among the four hypertensive groups in any variable of systolic or diastolic function of the heart. The results suggest that left ventricular hypertrophy is more pronounced in patients with primary aldosteronism than in patients with other forms of hypertension. It is therefore important to echocardiographically evaluate cardiac hypertrophy as a risk factor of morbidity and mortality in patients with this low renin hypertension.

Adrenal Gland Neoplasms↗