Biomedical subjects

T Ogihara

Publications and source records attributed to T Ogihara.

At least 631 records · Page 35Linked to original sources

PubMed1991

Analysis of mucosal blood hemoglobin distribution in gastric ulcers by computerized color display on electronic endoscopy.

A technique of computerized color display was used to analyze the mucosal blood hemoglobin distribution in patients with gastric ulcers. Using an electronic endoscope, red and green images (Vr and Vg) obtained separately from the electronic endoscopic image were transferred to an image analyzer and a computer. The mucosal hemoglobin content was calculated at each pixel of the image using the formula: index of hemoglobin content = 32[log2(Vr/Vg)]. Forty endoscopy examinations were performed in 15 patients with small ulcers (less than or equal to 1 cm) in the gastric angle and 5 normal subjects. The index of hemoglobin content ranged from 24 to 40 in the normal subjects. The index for the area around an active ulcer was mostly below 33. In cases of ulcers in the healing stage it increased to more than 40. The index was still above 40 in ulcer scars in the S1 stage, but within normal range in most of the mucosa in the S2 stage. Thus, the mucosal blood hemoglobin distribution can be assessed by computerized color analysis in patients with gastric ulcers at various stages.

Data Display↗

PubMed1991

Molecular nature of aldosterone synthase, a member of cytochrome P-450(11 beta) family.

The molecular nature of the aldosterone synthesizing enzymes of cattle and rat is discussed. In bovine adrenal cortex, one molecular species of cytochrome P-450(11 beta) catalyzes aldosterone synthesis as well as 11 beta-hydroxylation. The intactness of the mitochondrial membrane surrounding P-450(11 beta) in the zonae fasciculata-reticularis is essential to keep the aldosterone synthesizing activity of the cytochrome in these zones latent. In rat adrenal cortex, two distinct molecules belonging to a P-450(11 beta) family exist. One is 11 beta-hydroxylase, and the other aldosterone synthase.

Adrenal Cortex↗

PubMed1991

Clinical evaluation of delapril in Japan. Report from the Japan Study Group on Delapril.

Delapril, a new angiotensin converting enzyme (ACE) inhibitor discovered in the laboratory of Takeda Chemical Industries, Ltd., is the result of drug design based on the structure-activity relationships of ACE inhibitors. Delapril is an antihypertensive agent with a relatively long duration of action and no SH moiety in its structure. Following administration, it is converted into two active metabolites. Delapril effectively lowered blood pressure in 73% of 1,008 patients with hypertension during clinical trials in Japan. Efficacy rates were 73% for essential hypertension, 85% for renal hypertension, and 80% for renovascular hypertension. Excellent hypotensive response was observed in all age groups, from young to elderly patients. Side effects during administration of delapril, based on subjective evidence, were reported in 80 out of the 1,008 cases (7.9%). The main symptoms included orthostatic dizziness (1.7%), dizziness (1.3%), and nausea (1.1%). Dry cough, which has attracted attention in recent years as a side effect of ACE inhibitors, was reported at a low incidence of 1.1%. In a double-blind, controlled study in patients with mild to moderate essential hypertension in which captopril served as a positive control, delapril showed superior hypotensive effect and greater safety. Data derived from the Japan Study Group on Delapril indicate that this ACE inhibitor has excellent hypotensive effects and a high level of safety. It is suitable as a first-line drug in both monotherapy and combined therapy.

Adolescent↗

PubMed1991

Comparative study of the effects of three angiotensin converting enzyme inhibitors on the cough reflex.

To compare the effects of three different angiotensin converting enzyme (ACE) inhibitors on the cough reflex, capsaicin and citric acid challenge tests were done in normal subjects and hypertensive patients before and after administration of delapril, captopril, or enalapril. Two groups of 7 normal subjects (single dose study: 15 mg delapril v 18.75 mg captopril or 2.5 mg enalapril) and a group of 6 mildly hypertensive patients (1 week study: cross-over administration of 30 mg/day delapril, 37.5 mg/day captopril, or 5 mg/day enalapril) were studied. Another group of 6 patients with essential hypertension was treated with three ACE inhibitors for 4 weeks in a randomized order, with a 2 week washout period between active therapies. Aerosols of 1 mumol/L and 3 mumol/L capsaicin and 0.68% citric acid in 0.9% NaCl were generated by an ultrasonic nebulizer, and the frequency of cough was counted during inhalation. Delapril treatment resulted in substantially fewer patients with a significant increase (greater than or equal to 4 coughs during treatment than during the control period) in the frequency of cough than did captopril treatment. In the 1 and 4 week studies, enalapril and captopril had substantially more occurrences of significantly increased capsaicin-induced cough than did delapril. These results indicate that delapril has the least cough stimulatory effect among these ACE inhibitors, which may be clinically beneficial.

Administration, Inhalation↗

PubMed1991

Angiotensin converting enzyme inhibitors suppress the vascular renin-angiotensin system of spontaneously hypertensive rats.

The effects of angiotensin converting enzyme (ACE) inhibitors on the release of angiotensin II (Ang II) from isolated mesenteric arteries of spontaneously hypertensive rats (SHRs) were examined. Delapril, enalapril, and captopril suppressed Ang II release in a dose-dependent manner. After oral treatment with delapril (10 mg/kg/day), enalapril (10 mg/kg/day), and captopril (50 mg/kg/day) for 1 week, the blood pressure of SHRs was significantly reduced in the three groups and 54%, 46%, and 36% decreases in basal Ang II release were observed, respectively, compared with control. However, low-dose captopril (10 mg/kg/day) had no effect on blood pressure or basal Ang II release. These results provide clear evidence that ACE inhibitors suppress vascular renin-angiotensin activity of SHRs, and the possible contribution of the tissue renin-angiotensin system to spontaneous hypertension is suggested.

Angiotensin II↗

PubMed1991

Contribution of the activation of the ras oncogene to the evolution of aldosterone- and renin-secreting tumors.

The possible point-mutational activation of the ras oncogene, which probably contributes to the evolution of aldosterone-producing adenomas and ectopic reninoma, was evaluated. Chromosomal DNA was extracted from six aldosterone-producing adenomas and one renin-secreting liver carcinoma, using the standard method with phenol:chloroform:isoamyl alcohol. One microgram of sample DNA, forward and reverse primers, Taq I polymerase and deoxyribonucleotide triphosphates (dNTPs) were mixed and the ras gene was amplified by the polymerase chain reaction. Point mutations at ras-12 or ras-61 sites of amplified DNA were tested by dot-blotting, using H-, N- and K-ras oligonucleotide probes with mutations at codons 12 or 61. However, there were no point mutations at amino acid codons 12 or 61 of c-Hi-ras, c-Ki-ras and N-ras oncogenes in all aldosterone-producing adenomas and the one ectopic reninoma. These results indicate that point-mutational activation of ras oncogenes does not contribute, at least in this series, towards the evolution of aldosterone-producing adenomas and the reninoma.

Adenoma↗

PubMed1991

Changes in gene expression of the renin-angiotensin system in two-kidney, one clip hypertensive rats.

To investigate the molecular mechanism of sustained hypertension in two-kidney, one clip (2K1C) hypertensive rats, possible changes in renin gene expression in the kidney and angiotensinogen in the liver were studied. In 2K1C rats 4 weeks after clipping, the plasma renin and angiotensin II levels were significantly higher than those in sham-operated rats, but the plasma angiotensinogen levels were similar in the two groups. At this time, expression of the renin gene in the ischaemic kidney of 2K1C rats was 2.6-times that in sham-operated rats (P less than 0.05), but expressions of the angiotensinogen gene were similar in the two groups. Sixteen weeks after clipping, the plasma renin and angiotensin II levels in 2K1C rats were not significantly higher than those in sham-operated controls, but expression of the renin gene in the kidney was still 2.2-times higher in 2K1C rats than in controls (P less than 0.05). The plasma angiotensinogen level was significantly higher in 2K1C rats than in controls (P less than 0.05), and expression of the angiotensinogen gene in the liver was 2.9-times higher in 2K1C rats than in controls (P less than 0.01). These results indicate that the roles of the renin-angiotensin system in maintenance of hypertension in 2K1C rats differ in the acute and chronic phases: in the acute phase, over-expression of the renal renin gene coupled to increased renin secretion plays the major role in elevating the blood pressure; in the chronic phase, a counter-regulatory mechanism may affect the post-transcriptional fate of renin.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen↗

PubMed1991

Converting enzyme inhibitors regressed cardiac hypertrophy and reduced tissue angiotensin II in spontaneously hypertensive rats.

To examine the role of the tissue renin-angiotensin system in left ventricular hypertrophy, converting enzyme inhibitors were administered orally to 12-week-old male spontaneously hypertensive rats (SHR) for 4 weeks, and cardiac tissue angiotensin II was measured. Treatment with enalapril (10 mg/kg per day) and trandolapril (1 mg/kg per day) lowered systolic blood pressure, left ventricular weight and left ventricular angiotensin II content. Plasma angiotensin II concentration was increased by the treatment with enalapril whereas trandolapril did not cause any change. There was significantly positive correlation between left ventricular weight and angiotensin II content. Because angiotensin II promotes cell proliferation, these results suggest that cardiac tissue angiotensin II, rather than circulating angiotensin II, may account for the pathophysiology of left ventricular hypertrophy in SHR.

Angiotensin II↗

PubMed1991

Endothelin modulates L-NG-nitroarginine-induced enhancement of vasoconstriction evoked by norepinephrine.

The interaction of endothelin-1 (ET-1), a novel vasoconstrictor peptide synthesized according to the encoded amino acid sequence, with L-NG-nitroarginine (NOARG), an L-arginine-reversible inhibitor of endothelium-derived relaxing factor (EDRF) on adrenergic receptors, was investigated. Male Sprague-Dawley rats were used in this study. Mesenteric arteries were isolated and perfused with Krebs-Ringer solution at a constant flow rate. The vasoconstrictor responses to exogenous norepinephrine were determined. Low concentrations of ET-1 (10(-11) and 10(-10) M) potentiated the pressor responses to norepinephrine without affecting the baseline perfusion pressure. Simultaneous NOARG (10(-5) M) infusion with ET-1 (10(-11) M) into the mesenteric arteries caused further enhancement of the pressor responses to exogenous norepinephrine (200 ng) without affecting the baseline perfusion pressure: 126 +/- 15% to 262 +/- 45% (p less than 0.05, vehicle control: 100%). This facilitatory effect of NOARG on the pressor response to norepinephrine was attenuated with L-arginine (10(-4) M) infusion, but not D-arginine. These results suggest that ET, one of the endothelium-derived vasoconstricting factors, interacts with EDRF to modulate the tone of resistance vessels.

Animals↗

PubMed1991

Interleukin-6 stimulates proliferation of cultured vascular smooth muscle cells independently of interleukin-1 beta.

The effects of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) on proliferation of cultured vascular smooth muscle cells (VSMCs) were investigated. Treatment with IL-6 caused a rapid increase in the c-myc mRNA level, and resulted in increases in DNA synthesis and cell number. IL-1 beta stimulated the DNA synthesis of the cells. EGF showed synergistic and PDGF or IL-1 beta showed additive effects with IL-6 on the DNA synthesis. These results suggest that IL-6, independently of IL-1 beta, may be important in the proliferation of VSMCs.

Animals↗

PubMed1991

Effects of antihypertensive treatment on cardiac hypertrophy and cardiac function in elderly hypertensive patients.

The effects of antihypertensive treatment with calcium antagonists or angiotensin-converting enzyme (ACE) inhibitors on the reversal of left ventricular hypertrophy and the left ventricular function in elderly hypertensive patients were examined. Twenty-four elderly hypertensive patients with cardiac hypertrophy, aged from 65 to 79 years (mean +/- SEM of 71 +/- 1 years), were treated with a calcium antagonist (nifedipine or nicardipine) or ACE inhibitor (captopril or enalapril) for 3 months. Thirteen patients had essential hypertension [EH: systolic blood pressure (SBP) greater than or equal to 160 mm Hg and diastolic blood pressure (DBP) greater than or equal to 90 mm Hg, aged 70 +/- 1 years] and 11 had isolated systolic hypertension (ISH:SBP greater than or equal to 160 mm Hg and DBP less than 90 mm Hg, aged 74 +/- 2 years). All patients underwent M-mode echocardiography to assess left ventricular mass index (LVMI) and left ventricular function (ejection fraction, EF) before and after 3 months of treatment. BP significantly decreased from 174 +/- 3/97 +/- 1 to 144 +/- 5/84 +/- 2 mm Hg in EH and from 167 +/- 3/82 +/- 2 to 144 +/- 4/74 +/- 2 mm Hg in ISH. The LVMI was also significantly reduced from 204 +/- 14 to 174 +/- 16 g/m2 in EH and from 179 +/- 14 to 156 +/- 12 g/m2 in ISH. EF showed no significant changes with treatment in either group. In elderly hypertensive patients, the antihypertensive treatment with calcium antagonist or ACE inhibitor reduced cardiac hypertrophy without any deterioration of left ventricular function in both essential hypertension and isolated systolic hypertension.

Aged↗

PubMed1991

Orthostatic and postprandial blood pressure reduction in patients with essential hypertension.

1. The role of the sympathetic nervous system in orthostatic and postprandial blood pressure reduction in patients with essential hypertension was studied in 13 hypertensive patients and 10 age-matched normotensive subjects. 2. The blood pressure (BP), pulse rate, and plasma norepinephrine (NE) were measured: (i) every minute for 20 min in the upright position after overnight recumbency (ii) every 30 min after food intake for 3 h in the supine position. 3. Orthostatic BP reduction (greater than 13 mmHg in mean BP) was observed in eight hypertensive patients with a maximum after 4 min. Seven of these patients showed postprandial hypotension (greater than 13 mmHg) with a maximum 90 min after eating, while none of the normotensives exhibited such BP reductions. Before and during the tests the plasma NE levels were higher in hypertensive patients than in the normotensives. The plasma NE level was increased from 370 +/- 80 to 790 +/- 110 pg/mL 4 min after standing (P less than 0.01) in hypertensive patients and from 220 +/- 40 to 530 +/- 90 pg/mL (P less than 0.01) in normotensive subjects. The plasma NE level was decreased 90 min after food intake from 390 +/- 90 to 260 +/- 80 pg/mL in hypertensives. Changes in plasma NE correlated with those in mean BP after standing for 4 min (r = 0.379, P less than 0.05) and also with those 90 min after food intake (r = 0.457, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Calcium metabolism in elderly hypertensive patients: possible participation of exaggerated sodium, calcium and phosphate excretion.

1. Renal handling of electrolytes, including calcium (Ca), in response to physiological saline infusion (20 mL/kg, i.v., for 2 h) as well as basal circulating levels of Ca-regulating hormones were compared in 27 hypertensive elderly females (mean age 80 +/- 9 years), in 44 normotensive elderly females (79 +/- 9 years) and in 19 young normotensive females (23 +/- 4 years). 2. The hypertensive elderly females showed excessive increase in urine volume and urinary excretions of sodium (Na), Ca and inorganic phosphate (P) in response to saline infusion, associated with slight but significant decrease in circulating levels of Na and ionized Ca compared with those in the other groups. These hypertensive elderly patients also showed characteristic features both in circulating blood pressure and Ca regulating factors; they showed significantly low levels of plasma renin activity and aldosterone concentration, significantly high plasma levels of atrial natriuretic peptide and noradrenalin, compared with those in young controls and normotensive elderly females. 3. Moreover they showed significant increase in basal serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D, and significant decrease in basal serum levels of calcitonin, 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D, compared with those in the other groups. 4. These results suggest that the exaggerated natriuresis associated with excessive loss of Ca and P in urine may participate in the abnormality of Ca metabolism in low-renin hypertensive elderly patients.

Adult↗

PubMed1991

Consistent activation of prorenin mRNA in renal hypertensive rats.

To investigate the mechanism of maintaining hypertension in chronic two-kidney, one-clip (2K1C) rats, we studied the expression of the kidney renin gene. Total cellular RNA was extracted by the guanidine thiocyanate--CsCl method. Kidney renin messenger RNA was quantified by densitometric Northern blot analysis using 32P-labeled rat renin genomic DNA as a hybridization probe. Sixteen weeks after clipping, plasma renin concentration and plasma angiotensin II concentration did not differ between 2K1C and sham-operated rats (plasma renin activity, sham rats 16.2 +/- 4.2 vs. 2K1C rats 8.9 +/- 1.3 ng angiotensin I.mL-1.h-1; plasma angiotensin II, sham rats 14.7 +/- 7.5 vs. 2K1C rats 6.8 +/- 1.3 pg/mL), while plasma angiotensin concentration in 2K1C rats was higher than that of sham rats (p less than 0.05). Renin gene expression in the ischemic kidney was 2.2 times higher than that in the kidney of sham-operated rats (p less than 0.05), and decreased to 80% of those in the kidneys of sham-operated rats. These results suggest that overexpression of the kidney renin gene in the chronic phases of 2K1C rats may contribute to the sustained high blood pressure, and the kidney renin gene may be inhibited by posttranscriptional factors, i.e., suppressed activation of prorenin to renin.

Animals↗

PubMed1991

Increases in circulating level of platelet-activating factor lag behind transient neutropenia during hemodialysis with cuprophane membranes.

The significance of the level of circulating 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphorylcholine (C16-PAF, platelet-activating factor) in relation to transient neutropenia during hemodialysis with cuprophane membranes was examined. The neutrophil count was transiently and significantly decreased at 30 min after the start of hemodialysis, and it then gradually recovered during the period from 60 to 240 min after the start. Mirror image changes were observed in the circulating levels of C3a and C5a, suggesting that the decrease in the neutrophil count was triggered by activation of the complement factors. The circulating level of C16-PAF, although being similar to the basal level after 30 min of hemodialysis, was significantly increased after 60 and 120 min of hemodialysis. These data indicate that the increase in the circulating PAF level is not a direct cause of the transient decrease in the neutrophil count, but may be the result of activated neutrophils during hemodialysis with cuprophane membranes.

Adult↗

PubMed1991

Exaggerated natri-calci-uresis and increased circulating levels of parathyroid hormone and 1,25-dihydroxyvitamin D in patients with senile hypertension.

Renal handling of Na and Ca in response to physiological saline infusion (20 ml/kg i.v. for 2 h) was compared between 27 hypertensive (mean +/- SD age 79.8 +/- 9.2 years) and 44 normotensive (79.1 +/- 4.1 years) senile females. Compared to the normotensive group, the hypertensive group showed statistically significant decreases in the basal values of serum Ca and PRA, and significant increases in basal circulating levels of parathyroid hormone and 1,25(OH)2D and in urinary excretions of Na, Ca and Pi in the 2-hour urine specimens during the saline infusion. These results suggest that the excessive excretions of Ca and Pi associated with exaggerated natriuresis may participate in aberration of Ca metabolism in low-renin hypertensive seniles.

Absorption↗

PubMed1991

Intracellular signal transduction evoked by low-density lipoprotein in vascular smooth muscle cells.

Low-density lipoprotein (LDL) is a well-known causal factor in the development of arteriosclerosis. In the present study, we evaluated LDL-evoked cellular signal transduction in cultured rat vascular smooth muscle cells (VSMC). The addition of LDL at concentrations of more than 50 ng/ml, and apolipoprotein B (Apo-B) at more than 5 ng/ml, induced rapid but transient increases in the inositol 1,4,5-trisphosphate (InsP3) level, and caused rapid phasic and subsequent tonic increases in cytosolic free Ca2+ concentration [( Ca2+]i) in a dose-dependent manner in VSMC. LDL and Apo-B also caused transient acidification followed by Na(+)-dependent and amiloride-sensitive alkalization of the cells due to stimulation of a Na+/H+ exchanger. The enhancement of thymidine incorporation induced by the addition of LDL correlated well with the degree of increment of [Ca2+]i increases by the lipoprotein. These results suggest that an increase in [Ca2+]i mediated by InsP3 and intracellular alkalization may function as an important signal for enhanced DNA synthesis induced by LDL in VSMC.

Amiloride↗

PubMed1991

Susceptibility of neonatal lipoproteins to oxidative stress.

We compared peroxidizability of neonatal and adult lipoproteins exposed to oxidative stress initiated by an azo-compound. Oxygen uptake showed a two-phase pattern, with slow oxygen uptake in the first phase and faster uptake in the second phase. During the first phase, tocopherol was consumed progressively, inhibiting lipid peroxidation by scavenging peroxy radicals. After the tocopherol concentration fell below a critical level, extensive propagation of chain oxidative reactions produced the rapid oxygen uptake in the second phase. In the first phase of neonatal lipoprotein oxidation, a faster oxygen uptake was observed and the length of this phase was shorter than in adults. The oxygen uptake rate in the second phase was smaller in the neonatal lipoproteins. In other words, neonatal lipoproteins were more susceptible to oxidative stress than were adult ones when tocopherol remained in lipoproteins, but after tocopherol depletion the reverse was true. These results were consistent with the finding that in neonatal lipoproteins the tocopherol/lipid ratio was significantly lower (length of the inhibitory phase was closely correlated to the lipoprotein tocopherol content). In addition, the average number of active bisallylic hydrogen atoms, which are considered to determine the relative susceptibility of polyunsaturated fatty acids to oxidation, was significantly smaller (oxygen uptake rate in the second phase was closely correlated to the active bisallylic hydrogen number) in neonatal lipoproteins, and the ratio of active bisallylic hydrogen to tocopherol content (which closely correlated to oxygen uptake rate in the first phase) was also significantly lower compared with the adult ratio. Under physiologic conditions, an intensive oxidation of lipoproteins sufficient to cause lipoprotein tocopherol to fall below critical levels is unlikely to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗