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Biomedical subjects

T Ishimitsu

Publications and source records attributed to T Ishimitsu.

At least 73 records · Page 4Linked to original sources
PubMed1996

[A case of herniation through a defect in the falciform ligament at late pregnancy].

A very rare case of small bowel strangulation caused by herniation of a loop of ileum through a defect in the falciform ligament is reported. A 27-year-old woman in the 38 weeks and 5 days of pregnancy was admitted with a sudden onset of epigastralgia. Emergency laparotomy with cesarean section was performed. A strangulated loop of ileum was found to pass through a defect in the falciform ligament. The ligamentum teres was divided to release the obstruction and the irreversible strangulated loop was resected. The strangulation was considered to have occurred because a loop of small bowel compressed by gestational uterus passed through a congenital defect in the falciform ligament.

Adult↗
PubMed1995

Increased plasma levels of adrenomedullin in patients with heart failure.

OBJECTIVES: To investigate the role of adrenomedullin in the pathophysiology of heart failure, we measured plasma levels of adrenomedullin in patients with heart failure. BACKGROUND: Adrenomedullin is a potent hypotensive peptide newly discovered in pheochromocytoma tissue by monitoring its elevating activity on platelet adenosine 3',5'-cyclic monophosphate (cAMP). A significant level of adrenomedullin has been identified in human plasma. These findings suggest the possibility of adrenomedullin as a new circulating hormone that participates in the regulation of the cardiovascular system. METHODS: Venous blood samples at rest were obtained from patients with heart failure in New York Heart Association functional classes I (n = 15), II (n = 25), III (n = 16) and i.v. (n = 10) and from normal subjects (n = 27). Plasma adrenomedullin levels were determined by our newly developed radioimmunoassay. Other humoral factor levels measured simultaneously included norepinephrine, atrial natriuretic peptide, brain natriuretic peptide, plasma renin activity, aldosterone and cAMP. Left ventricular ejection fraction was measured by echocardiography. In eight patients with severe heart failure, plasma adrenomedullin levels were measured before and after treatment. RESULTS: The mean (+/- SD) plasma level of adrenomedullin in control subjects was 2.52 +/- 0.75 pmol/liter. Plasma levels of adrenomedullin in patients with heart failure were unaffected in those in functional class I (2.85 +/- 0.62 pmol/liter) but tended to be increased in those in class II (3.54 +/- 0.82 pmol/liter) and were significantly increased in those in classes III and i.v. (4.78 +/- 1.218 and 8.74 +/- 3.43 pmol/liter, respectively). There was a significant correlation between plasma levels of adrenomedullin and norepinephrine (r = 0.618, p < 0.001), atrial natriuretic peptide (r = 0.696, p < 0.001) and brain natriuretic peptide (r = 0.692, p < 0.001). Left ventricular ejection fraction inversely correlated with plasma adrenomedullin levels (r = 0.485, p < 0.001). Plasma adrenomedullin levels significantly decreased after treatment (from 7.40 +/- 3.40 to 3.98 +/- 1.00 pmol/liter, p < 0.05). CONCLUSIONS: These results suggest that plasma level of adrenomedullin are elevated in heart failure and that an increased plasma volume and an activated sympathetic nervous system in this condition may be related to its synthesis or secretion. Given that adrenomedullin exerts potent cardiovascular effects, increased adrenomedullin may be involved in the defense mechanism against further peripheral vascular resistance elevation in heart failure.

Adrenomedullin↗
PubMed1995

Effect of high potassium diets on the vascular and renal prostaglandin system in stroke-prone spontaneously hypertensive rats.

High potassium (K) diets are known to have a protective effect on the endothelium and the kidney against hypertensive injury independent of blood pressure change. Vasodepressor prostaglandins (PGs) have been shown to be cytoprotective in various tissues. This study investigated the effect of high K diets on the vascular and renal eicosanoid system in stroke-prone spontaneously hypertensive rats (SHRsp). Eicosanoid production by the aorta and eicosanoid content in the renal cortex were examined in SHRsp rats fed high NaCl diets containing either 0.5% K (normal) or 2.1% K (high). Although the high K diet did not affect the blood pressure, SHRsp on the high K diet had less thickening of the aortic wall than SHRsp on the normal K diet (-15%, p < 0.001). The aortic strip of the high K SHRsp produced less vasodepressor PG than that of the normal K SHRsp when they were incubated in a medium (PGI2 -45%, p < 0.003; PGE2 -34%, p < 0.001). Furthermore, when the aorta was perfused in a chamber at hypertensive pressure, again the high K aorta showed reduced PGI2 production as compared with the normal K aorta (intravascular side -52%, p < 0.01). Eicosanoid content in the renal cortex was not significantly different between the normal K and the high K SHRsp (PGI2 79 vs 87 ng/g dry weight; PGE2 214 vs 233 ng/g dry weight). Thus, the high K diet reduced vascular eicosanoid production but did not alter eicosanoid content in the renal cortex. The reduced vascular eicosanoid production in the high K SHRsp may reflect the reduced necessity for cytoprotective vasodepressor PG against vascular injuries.

Administration, Oral↗
PubMed1994

Genomic structure of human adrenomedullin gene.

Adrenomedullin (AM) is a potent hypotensive peptide recently discovered from human pheochromocytoma tissue by its stimulating activity of platelet cAMP production. In this study, we have isolated the gene for human AM from a human genomic library and determined its structure. The genomic DNA of human AM consists of 4 exons and 3 introns, and the 5' flanking region contains TATA, CAAT and GC boxes. There are also multiple binding sites for activator protein-2 (AP-2) and a cAMP-regulated enhancer element. Southern blot analyses revealed that the AM gene is situated in a single locus of chromosome 11. These indicate that the human AM gene has components for its functional expression and that the expression may be subject to the activity of protein kinase C and the feedback from cAMP level.

Adrenal Gland Neoplasms↗
PubMed1994

Vasoconstrictors and renal protection induced by beta 1-selective adrenoceptor antagonist bisoprolol.

We investigated the role of the vasoconstrictors endothelin-1 (ET-1) and thromboxane in renal protection by the beta 1-selective adrenoceptor antagonist, bisoprolol, in Dahl salt-sensitive rats (Dahl S) and salt-resistant rats (Dahl R). Six-week bisoprolol treatment (20 mg/kg chow) reduced systolic blood pressure (SBP) by 14% in Dahl S rats fed a high-salt (4% NaCl) diet. This BP reduction was accompanied by a decrease in aortic wall thickness. ET-1 and thromboxane released from renal cortex was significantly decreased by 17 and 30% with bisoprolol, respectively. Other prostaglandin synthesis was unaffected. Renal function such as proteinuria, N-acetyl-beta-D-glucosaminidase (NAG) excretion, and glomerular filtration rate (GFR) was not influenced by bisoprolol. Morphologic investigation showed that bisoprolol significantly improved glomerular sclerosis by 29% and attenuated arterial damage by 71%, although tubular injury was not affected. The more severe the glomerulosclerotic lesions, the greater the generation of thromboxane and ET. The arterial lesions were positively correlated to thromboxane generation. These data indicate that long-term bisoprolol treatment reduces vasoconstrictive ET-1 and thromboxane generation and that these alterations may be partly responsible for the amelioration of glomerular and arterial injury in Dahl S rats.

Adrenergic beta-1 Receptor Antagonists↗
PubMed1994

Antihypertensive property and renal protection by shichimotsu-koka-to extract in salt-induced hypertension in Dahl strain rats.

We determined whether or not the kampo formula, Shichimotsu-koka-to extract, attenuates the development of salt-induced hypertension and provides renal protection against hypertensive injury in Dahl salt-sensitive (Dahl S) rats. A six-week treatment using this formula dose-dependently decreased the systolic blood pressure in Dahl S rats fed a high-salt (2% NaCl) diet. This blood pressure reduction was associated with a decrease in the thickness of the aortic wall. Renal function was not altered with this treatment; however, glomerular sclerotic lesions in the kidney were significantly attenuated. Neither arterial nor tubular lesions were affected. These data suggest that Shichimotsukoka-to extract exhibits an antihypertensive effect which is associated with partial resolution of glomerular sclerosis in the kidney.

Animals↗
PubMed1994

Different effects between antihypertensive drugs on nephrotic-range proteinuria in renovascular hypertension.

A 61-year-old man developed renovascular hypertension characterized by nephrotic-range proteinuria. When he was treated with a calcium channel blocker, glomerular filtration fraction was 0.26 and massive proteinuria ranging from 10 to 15 g/day persisted. An angiotensin-converting enzyme inhibitor markedly reduced the proteinuria to 1-2 g/day with a filtration fraction of 0.20. After the antihypertensive drug was switched to a beta-blocker, the filtration fraction was 0.23 and urinary protein excretion was 3-4 g/day. Blood pressure control was comparable by each drug. These findings suggest a role of intraglomerular hydraulic mechanism in the etiology of massive proteinuria in renovascular hypertension.

Adrenergic beta-Antagonists↗
PubMed1994

Antihypertensive effect of interleukin-2 in salt-sensitive Dahl rats.

We investigated the effects of interleukin-2, which stimulates the proliferation and maturation of thymus-derived lymphocytes, on hypertension and organ injuries in genetically hypertensive rats. Interleukin-2 (5 x 10(4) U/kg body wt) was subcutaneously injected into Dahl salt-sensitive rats fed a 4% NaCl diet and spontaneously hypertensive rats once a week for 10 weeks. The effects on blood pressure, cardiovascular hypertrophy, and renal function were evaluated. Interleukin-2 treatment lowered blood pressure in Dahl salt-sensitive rats (162 versus 187 mm Hg, P < .005). This antihypertensive effect was associated with an increase in glomerular filtration rate (589 versus 428 mL/d per 100 g body weight, P < .005) and reduction in cardiac weight (268 versus 305 mg/100 g body weight, P < .05). Interleukin-2 also alleviated the marked glomerular sclerosis in Dahl salt-sensitive rats (glomerular injury score, 151 versus 220; P < .001). In contrast, interleukin-2 did not affect the development of hypertension or organ injuries in spontaneously hypertensive rats. Histologically, glomerular and arterial lesions of the kidney were much less marked in spontaneously hypertensive rats than in Dahl salt-sensitive rats. These data indicate that interleukin-2 ameliorates the development of hypertension and cardiac and renal injuries in Dahl salt-sensitive rats.

Animals↗
PubMed1994

Clinical studies on the sites of production and clearance of circulating adrenomedullin in human subjects.

Adrenomedullin is a novel hypotensive peptide, newly discovered in pheochromocytoma. Because immunoreactive adrenomedullin is present in human plasma, adrenomedullin may play a role in regulating blood pressure. A recent report showed that human adrenomedullin mRNA is expressed not only in pheochromocytoma but also in the normal adrenal medulla, kidney, lung, and ventricle. However, whether or not these organs actually release adrenomedullin into the circulation remains unknown. To investigate the sites of production and degradation of adrenomedullin in human subjects, we obtained blood samples from various sites and measured immunoreactive adrenomedullin concentrations. In study 1, blood samples were obtained from the infrarenal inferior vena cava, suprarenal inferior vena cava, superior vena cava, right atrium, right ventricle, pulmonary artery, pulmonary capillary, left ventricle, and aorta during cardiac catheterization in 15 patients with ischemic heart disease (67 +/- 10 years). In study 2, blood samples were taken from the infrarenal inferior vena cava, suprarenal inferior vena cava, right and left renal veins, and left adrenal vein in 5 hypertensive patients (42 +/- 14 years) suspected of having renovascular hypertension. In study 3, peripheral venous blood samples were obtained in 2 patients (males, 45 and 36 years old) with pheochromocytoma at rest and during hypertensive attacks. Plasma adrenomedullin concentrations were measured by a newly developed radioimmunoassay. In study 1, there were no significant differences in plasma adrenomedullin concentrations in various sites of the right-side circulation. There was no step-up of plasma adrenomedullin levels in the coronary sinus. However, the plasma concentration of adrenomedullin in aorta was slightly but significantly lower than in pulmonary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1994

Plasma levels of adrenomedullin, a newly identified hypotensive peptide, in patients with hypertension and renal failure.

Adrenomedullin is a potent hypotensive peptide newly discovered in pheochromocytoma tissue by monitoring its elevating activity on platelet cAMP. We measured plasma concentration of adrenomedullin in patients with essential hypertension and chronic renal failure. As compared with normal subjects, plasma adrenomedullin was increased by 26% (P < 0.05) in hypertensives without organ damage and by 45% (P < 0.005) in those with organ damage. The increase in plasma adrenomedullin was more prominent in renal failure than in hypertension. Renal failure patients with plasma creatinine of 1.5-3, 3-6, and > 6 mg/dl had higher plasma adrenomedullin levels than healthy subjects by 78% (P < 0.05), 131% (P < 0.001), and 214% (P < 0.001), respectively. Moreover, adrenomedullin showed intimate correlations with norepinephrine, atrial natriuretic peptide, and cAMP in plasma (r = 0.625, P < 0.001; r = 0.656, P < 0.001; and r = 0.462, P < 0.001; respectively). Thus, plasma adrenomedullin is supposed to increase in association with changes in sympathetic nervous activity and body fluid volume in hypertension and renal failure. Considering its potent vasodilator effect, adrenomedullin may be involved in the defense mechanism preserving the integrity of the cardiovascular system in these disorders.

Adrenomedullin↗
PubMed1994

Benefits and demerits of antihypertensive therapy by high-dose calcium channel blocker in severely hypertensive rats.

This study examined the protective effects of a calcium channel blocker, nisoldipine (NSL), against organ damage secondary to severe hypertension. Severe hypertension was induced in male 7-week-old spontaneously hypertensive rats (n = 21) by heminephrectomy and substitution of 1% NaCl solution for drinking water. They were fed a chow containing 0%, 0.03% (low dose) or 0.1% (high dose) NSL for 12 weeks. The systolic blood pressures after 12 weeks were 228 mmHg in the control group, 201 in the low dose NSL group and 188 in the high dose NSL group. Body weight gain was blunted in the high dose NSL group (at 12 weeks: control 289g; low dose NSL 286; high dose NSL 263, p < 0.04). Although a further reduction in cardiac weight was seen in the high dose NSL rate (low NSL -5.2%, p < 0.05; high NSL -9%, p < 0.01), reductions in aortic thickness did not differ between the 2 doses (low NSL -18%, p < 0.001; high NSL -17%, p < 0.001). Moreover, dose-dependent effects of NSL treatment were absent for such endpoints as plasma creatinine (low NSL -15%, p < 0.04; high NSL -17%, p < 0.05), glomerular filtration rate (low NSL +21%, p < 0.05; high NSL +20%, p < 0.03) and urinary protein excretion (low NSL -22%, p < 0.05; high NSL -29%, p < 0.02). Thus, a high dose calcium channel blocker hampered growth and did not further improve vascular wall thickening or renal injury in severely hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Renoprotective effect of nisoldipine in rats with severe hypertension.

OBJECTIVE: To compare the protective effect against cardiac and renal damage of a beta-blocker, an angiotensin converting enzyme inhibitor and a calcium antagonist in severely hypertensive rats. METHODS: Six-week-old male spontaneously hypertensive rats (n = 24) were given 100 mg/kg deoxycorticosterone and a 4% NaCl diet. They were then treated orally with vehicle, atenolol (70 mg/kg), enalapril (5 mg/kg) or nisoldipine (7 mg/kg) for 8 weeks. RESULTS: Control (vehicle-treated) rats developed marked hypertension after 8 weeks. The antihypertensive effect of the three drugs was similar, as were the reductions achieved in cardiac weight and aortic thickness. However, histological examination revealed that nisoldipine was significantly more effective than the other drugs in reducing renal arteriolar lesions and renal glomerular sclerosis. Only nisoldipine significantly improved plasma creatinine and the glomerular filtration rate. CONCLUSION: These findings suggest that calcium antagonists have a renoprotective effect in severely hypertensive rats, which may derive from the inhibition of arteriolar damage and glomerular sclerosis.

Animals↗
PubMed1994

Protective effect of the calcium antagonist NKY-722 against renal and arterial injuries in Dahl salt-sensitive rats.

OBJECTIVE: To study the effect of long-term administration of NKY-722 and nicardipine on renal dysfunction and morphological changes in the kidneys and arteries in Dahl salt-sensitive (Dahl-S) rats. DESIGN: Vehicle, NKY-722 and nicardipine were administered orally to Dahl-S rats fed a high-salt diet for 6 weeks. METHODS: Systolic blood pressure was measured once a week. At the last week blood and urine were collected and an autopsy was carried out. RESULTS: NKY-722 (1 mg/kg per day) lowered blood pressure reproducibly for 6 weeks, whereas nicardipine (3 mg/kg per day) showed a similar effect at week 1 only. NKY-722 tended to decrease blood urea-nitrogen, and reduced plasma creatinine and renin activity significantly. NKY-722 increased urine volume, urinary sodium, creatinine and protein excretions, but did not affect urinary N-acetyl-beta-D-glucosaminidase activity significantly. NKY-722 increased the glomerular filtration rate and reduced glomerulosclerosis and renal arterial injury morphologically. Nicardipine did not affect blood or urinary parameters, but reduced glomerular injury significantly. NKY-722 but not nicardipine reduced cerebral arterial injury. A lower dose of NKY-722 (0.3 mg/kg per day) did not affect blood pressure, blood or urinary parameters, but reduced glomerulosclerosis and renal arterial injury significantly. NKY-722 (1 mg/kg per day) and nicardipine (3 mg/kg per day) increased urinary 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and PGE2. NKY-722 but not nicardipine increased the 6-keto-PGF1 alpha:thromboxane B2 ratio in the thoracic aorta. CONCLUSIONS: NKY-722 improved the renal dysfunction, and reduced glomerular, renal and cerebral arterial injuries in Dahl-S rats. The effect of NKY-722 on glomerulosclerosis and arterial injuries is, at least partly, independent of blood pressure, and is probably related to the effect on eicosanoid metabolism.

Animals↗
PubMed1993

An eosinophil chemotactic lymphokine in the supernatant of lymphokine-activated killer (LAK) cell culture: relationship to interleukin-5.

The administration of interleukin-2 (IL-2) systemically or locally to cancer patients, either alone or in combination with lymphokine-activated killer (LAK) cells, frequently results in eosinophilia. To investigate the mechanism of such eosinophil accumulation, we measured in vitro eosinophil chemotactic activity (ECA) in the supernatant of LAK cell cultures by a modified Boyden's chamber method. Consequently, a potent and specific ECA was found in the cell-free supernatant of LAK cell cultures. On the other hand, no ECA was found in the supernatant of normal lymphocyte cultures, nor in IL-2 itself. This activity plateaued when 3 x 10(6) lymphocytes were incubated with 1000 U/ml IL-2 for more than 3 days. Sephadex G-100 gel chromatography indicated that the molecular weight of this eosinophil chemotactic factor (ECF) was approximately 45,000 Da. The ECF was stable when heated to 56 degrees C for 30 min but was inactivated by trypsin, indicating that the ECF is a lymphokine which has very similar characteristics to those of IL-5. Using ELISA for hIL-5, the IL-5 level in the supernatant of LAK cell cultures increased dose dependently with increasing IL-2 concentrations. These results suggest that IL-5 may be responsible for the local recruitment of eosinophils in IL-2/LAK therapy.

Animals↗
PubMed1993

Genetic predisposition to hypertension facilitates blood pressure elevation in hemodialysis patients treated with erythropoietin.

PURPOSE: This study investigated the hypothesis that a genetic predisposition to hypertension is involved in the etiology of the elevation in blood pressure induced by human recombinant erythropoietin (rHuEPO). PATIENTS AND METHODS: Blood pressure changes after 10 weeks of treatment with rHuEPO were compared between 26 patients with a positive family history of hypertension and 27 with a negative family history. RESULTS: Mean blood pressure was significantly increased in patients with a positive family history of hypertension (+8.8 mm Hg, p < 0.001). In contrast, the change was not significant in those whose family history was negative (+1.8 mm Hg, not significant). The mean blood pressure of 14 of 26 patients with a positive family history of hypertension increased by more than 10%, whereas such an increase occurred in only 2 of 27 patients with a negative family history (p < 0.001). The two groups were similar in terms of the total dose of rHuEPO given, the degree to which their anemia improved, and their basal blood pressures. CONCLUSION: It appears that hemodialysis patients with a positive family history of hypertension are susceptible to developing hypertension during treatment with rHuEPO.

Antihypertensive Agents↗
PubMed1993

Direct vasopressor effects of erythropoietin in genetically hypertensive rats.

The purpose of this study is to compare the direct vasopressor effects of erythropoietin between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The aortic rings from SHR or WKY were suspended in tissue baths coupled with tension-recording devices. High concentrations of recombinant human erythropoietin (more than 20 U/ml) induced vasoconstriction in the aortic ring of genetically hypertensive SHR. Furthermore, only in SHR, 10 U/ml erythropoietin enhanced contraction induced by 10(-7) M norepinephrine (+145% vs +121%, p < 0.04) and reduced relaxation by 10(-7) M acetylcholine (-69% vs -96%, p < 0.05). On the other hand, erythropoietin did not influence the contractility of aortic ring in normotensive WKY. These results suggest that erythropoietin exhibits its direct vasopressor effect preferentially in the blood vessels of genetically hypertensive animals.

Acetylcholine↗
PubMed1993

[Effects of nisoldipine in heminephrectomized spontaneously hypertensive rats--measurement of afferent and efferent arterioles by microvascular cast].

In this study, we measured cross sectional areas of glomerular arterioles and glomerular volume in heminephrectomized spontaneously hypertensive rats (SHR) treated with a calcium antagonist, nisoldipine (NSL). We also examined the relevance of these parameters to the progression of hypertensive renal injury. Male 6-week-old SHR (n = 14) were heminephrectomized and divided into 2 groups. They were fed regular chow (control, n = 7) or chow containing 0.1% NSL (n = 7). After 12 weeks, urinary protein excretion (UpV) and systolic blood pressure (SBP) were measured. The control rats developed marked hypertension reaching 228 +/- 2 mmHg, and NSL lowered this by 27 mmHg (p < 0.001). NSL reduced UpV by 22% (p < 0.05). Microvascular cast of the kidney was prepared, and the cross sectional areas of the afferent and efferent arterioles as well as glomerular volume were measured using scanning electron microscopy. In the juxtamedullary and subcapsular glomeruli with minor abnormalities, the afferent arteriole was narrower and the glomerular volume was smaller in the NSL-treated rats than in the control rats. These results suggest that the calcium antagonist, NSL, offers the advantage of protecting kidney from hypertensive injury by reducing afferent arteriolar diameter, glomerular hypertrophy and intraglomerular pressure in heminephrectomized SHR.

Animals↗