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Biomedical subjects

T Kokubu

Publications and source records attributed to T Kokubu.

At least 91 records · Page 5Linked to original sources
PubMed1987

Enhanced blood pressure response to isometric handgrip exercise in patients with essential hypertension: effects of propranolol and prazosin.

To elucidate whether a difference exists in blood pressure (BP) elevation during isometric handgrip exercise (IHG) between essential hypertensives (EHT) and normotensives (NT), IHG was carried out in 12 NT and 46 EHT under constant sodium intake using a new instrument. The acute effects of propranolol and prazosin on IHG were also examined in EHT. The change in systolic BP (delta SBP) during IHG in EHT, delta SBP = 61 +/- 21 mmHg, was markedly greater than that in NT, delta SBP = 28 +/- 4 mmHg. Among EHT, delta BP increased with increasing severity of hypertension. Neither the changes in plasma norepinephrine nor in epinephrine during IHG showed significant differences between EHT and NT. The pressor response during IHG could not be suppressed by propranolol, but about 30% suppression of BP was observed during IHG with prazosin. It is concluded from these findings that EHT have an exaggerated BP response to IHG that is due to increased post-junctional alpha 1-adrenoceptors.

Adult↗
PubMed1987

In vitro inhibition of human renin by statine-containing tripeptide renin inhibitor (ES-1005).

Dipeptide and tripeptide derivatives containing a statine residue were synthesized as human renin inhibitors. ES-305, bis[(1-naphthyl)methyl]acetyl-histidyl-statine-2(S)-methylbutylami de, was found to be a highly potent human renin inhibitor that is species-specific and enzyme-specific. The replacement of the methylbutylamide of ES-305 with the leucyl-lysinol (ES-1005) showed similar high potency against human renin (Ki value of 2.4 x 10(-9) M) and monkey renin (Ki value of 7.9 x 10(-9) M) as ES-305. ES-1005 competitively inhibited human renin. The compound was about one order of magnitude less potent against pig, dog, and rabbit renins. It had moderate inhibitory potencies against cathepsin D and pepsin (IC50 of cathepsin D and pepsin of 1.6 x 10(-5) and 8.0 x 10(-6) M, respectively). ES-1005, a newly synthesized tripeptide derivative containing statine, is a highly potent inhibitor of not only primate renin but also a wide variety of nonprimate renins.

Animals↗
PubMed1987

Biochemistry of human converting enzyme.

Angiotensin converting enzyme (ACE, EC 3.4.15.1) was purified to homogeneity from human kidney and its specific antibody was raised in the rabbit. The antibody cross-reacted equally with human enzymes from kidney, lung, intestine, plasma and urine. Immunofluorescent and immunoelectron microscopic observation indicated that the enzyme was located on the plasma membrane and micropinocytic vesicles at the luminal site of vascular endothelium in the lung. It was also present on the brush border, intercellular and basal infolding membranes of proximal tubular epithelium, but was not detected on the distal tubular epithelium or vascular endothelium in the kidney. ACE was demonstrated immunocytologically in human alveolar macrophages and renal carcinoma tissues. The carcinoma tissue contained a possible isoenzyme of ACE differing in part immunologically from the enzyme of normal kidney.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Angiotensin converting enzyme in sarcoidosis and in silicosis.

Angiotensin converting enzyme (ACE) activities of bronchoalveolar lavage fluid (BALF) and serum in patients with sarcoidosis and with silicosis were measured. Serum ACE was measured by enzymic assay and radioimmunoassay. There was a close relationship between ACE activity and content (r = 0.78). Serum ACE activities in patients with active sarcoidosis (37.5 +/- 11.1 nmol/min/ml, mean +/- SD) and with silicosis (25.5 +/- 9.3) were significantly elevated from the control (18.6 +/- 6.0). BALF ACE activities in the control, patients with active sarcoidosis and with silicosis were 0.23 +/- 0.19 nmol/min/ml, 0.94 +/- 0.97 and 0.38 +/- 0.05, respectively. BALF ACE in patients with active sarcoidosis and with silicosis were significantly different from the control. When BALF ACE was corrected by the cell count of alveolar macrophage (per 10(6) cells), activity was significantly different from control only in the patients with sarcoidosis. Moreover, only the alveolar macrophages in sarcoidosis were stained by immunofluorescence and immunocytochemistry using rabbit antihuman ACE antibody. Induction of ACE in alveolar macrophage might have an important role for the activity or progression of sarcoidosis.

Adult↗
PubMed1987

The effect of low dose carvedilol on circadian variation of blood pressure in patients with essential hypertension.

The effect of once daily low-dose carvedilol on circadian variations of blood pressure (BP) was studied in Japanese patients with mild or moderate essential hypertension. Thirty-one patients were admitted to hospital whose BP was 150/90 mm Hg/day or greater and they participated in the study. After a placebo period of 1 week, 5 or 10 mg carvedilol was given once daily in the morning for 3 to 7 days, and if BP reduction was not sufficient, the dose was increased to 20 mg daily. The blood pressure variation was monitored before and 1, 2, 4, 6, 8, 10, 12, and 24 h after administration of the drug on the last day of placebo and final dose of carvedilol. Of the 31 cases receiving carvedilol once daily, cumulative effectiveness (13 mm Hg reduction in mean BP) was 48.4% at 10 mg/day and 54.8% at 20 mg/day. Both systolic and diastolic pressures decreased significantly and heart rate decreased slightly. There was no significant difference between the standard deviations of BP on the last days of the control period and the carvedilol treatment. The difference between maximum and minimum BP during the day was not significant between the two periods. Circadian variations of heart rate were also not significantly different for the two periods. This indicates that carvedilol did not have any effect on circadian variations of BP and heart rate. The present study also suggests that low-dose carvedilol once daily may be effective in the treatment of hypertension.

Adrenergic beta-Antagonists↗
PubMed1987

Brain glutathione and blood pressure control.

The role of glutathione in the central nervous system in regulating blood pressure (BP) and sympathetic nerve activity (SNA) was investigated in rats. Intracerebroventricular (ICV) injection of glutathione disulfide (GSSG: 1.7-33 nmol) resulted in a dose-dependent increase in BP [delta mean BP: 17 +/- 1 mm Hg (n = 7) for 33-nmol dose] together with a marked increase in SNA [163 +/- 13 to 672 +/- 70 spikes/10 s (n = 7), p less than 0.001]. Intracerebroventricular administration of its reduced form (GSH, 33 nmol) produced a vasodepressor response (delta mean BP: -9 +/- 2 mm Hg) accompanied by a corresponding decrease in SNA [192 +/- 15 to 54 +/- 22 spikes/10 s (n = 6), p less than 0.01]. These responses were not due to a leakage into the systemic circulation, since intravenous injection of GSSG or GSH (33 nmol) did not show any cardiovascular effects. Electrical stimulation of the posterior hypothalamus induced hypertension with a significant decrease of GSSG in the brain stem. The results indicate that GSSG has a stimulatory control over the sympathetic nervous system while GSH has an inhibitory effect on SNA. Glutathione disulfide and GSH may act within the central nervous system to modulate the tone of the sympathetic nervous system.

Adrenergic Fibers↗
PubMed1986

Isolation and characterization of a 34,000-dalton calmodulin- and F-actin-binding protein from chicken gizzard smooth muscle.

We isolated a 34,000-dalton protein from the heat-soluble fraction of avian smooth muscle using the procedures of ammonium sulfate fractionation, cation exchange chromatography and gel filtration. The amount of 34,000-dalton protein in the muscle homogenate was as much as tropomyosin. The 34,000-dalton protein bound to F-actin and F-actin-tropomyosin in a Ca2+-independent manner, but it Ca2+-dependently interacted with calmodulin. We tentatively named the 34,000-dalton protein gizzard p34K.

Actins↗
PubMed1986

Plasma half-life and organ uptake ratio of radiolabeled glandular kallikrein in control and nephrectomized rats.

The purified rat urinary kallikrein was radiolabeled by lactoperoxidase method and by chloramine T method. Plasma half-life of radiolabeled kallikrein was 5.06 +/- 0.59 (n = 5) min in control rats and 5.24 +/- 0.42 (n = 5) min in nephrectomized rats. There was no difference between two groups. From autoradiogram, main metabolic organs of radiolabeled kallikrein were liver, kidney and spleen. Total uptake of radiolabeled kallikrein in ech organ was the highest in liver (73.2%). The uptake per g tissue of radiolabeled kallikrein in each organ was high in liver (33.0%), kidney (31.4%) and spleen (21.1%). These results suggest that the active kallikrein is metabolized mainly in the liver, and kidney is not so an important organ to metabolize or to eliminate the active kallikrein in plasma. In order to clarify the mode of existence of active kallikrein in plasma, the following experiment was done by using disc gel electrophoresis. Radioactive profile of radiolabeled kallikrein showed one peak (Rf = 1.0), but radiolabeled kallikrein mixed with rat plasma showed two peaks, that is small peak (Rf = 1.0), and main peak (RF = 0.5). The most of radiolabeled kallikrein was bound to plasma protein and only five per cent was in free form. Furthermore, the binding of radiolabeled kallikrein to plasma protein was interfered by the addition of active kallikrein. These results suggest the possibility of existence of kallikrein binding protein in plasma.

Animals↗
PubMed1986

Statine-containing dipeptide and tripeptide inhibitors of human renin.

Dipeptide and tripeptide derivatives containing a statine residue were synthesized as inhibitors of human renin. ES-305, bis[(1-naphthyl)methyl]acetyl(BNMA)-histidyl-statine 2(S)-methylbutylamide was found to be a highly potent inhibitor of human renin with a Ki value of 1.7 X 10(-9) M. Dipeptide derivatives with the BNMA group at the N-terminal (BNMA-Val-Sta-isoleucinol [ES-313], BNMA-Leu-Sta-isoleucinol [ES-316], and BNMA-Nle-Sta-isoleucinol [ES-317]) had potencies against human renin that were similar to the potency of ES-305. All these dipeptide derivatives competitively inhibited human renin. The inhibitors were also potent against monkey renin but were less effective against renins from pig, goat, dog, rabbit, and rat. ES-305 had little effect on cathepsin D and pepsin at the concentration of 10(-5) M. The other derivatives showed detectable inhibition of cathepsin D (IC50, 10(-6) - 10(-7) M) and pepsin (10(-5) - 10(-6) M). All the compounds had little or no effect on trypsin, chymotrypsin, angiotensin converting enzyme, and urinary kallikrein at the concentration of 10(-5) M. Our results indicate that ES-305 is a highly potent and specific inhibitor of human renin. This compound is superior to other, previously described statine-containing renin inhibitors with respect to molecular size and enzyme specificity.

Amino Acids↗
PubMed1986

Clinical significance of early diastolic time intervals for the evaluation of left ventricular function in patients with coronary artery disease.

To investigate non-invasively the diagnostic significance of diastolic properties in coronary artery disease (CAD), the following early diastolic time intervals (EDTIs): IIA-O time (from the aortic component of the second heart sound to the O-point on the apexcardiogram), IIA-MVO time (from IIA to the mitral valve opening) and MVO-O time (from MVO to the O-point), were estimated in 18 patients with angina pectoris (AP) and 29 with old myocardial infarction (OMI) who were subdivided into two groups according to ejection fraction (EF): group I (OMI-I): more than 50% and group II (OMI-II): less than 50%. Seventeen patients without evidence of CAD were used as controls (N). Left ventricular pressure (LVP) and pulmonary capillary wedge pressure (PCWP) were measured simultaneously to clarify the relationship between EDTIs and early diastolic hemodynamics. IIA-O time and IIA-MVO time in AP, OMI-I and OMI-II were significantly longer than in N. This prolongation accorded with the reduction of left ventricular function. MVO-O time in AP and OMI-I also was significantly longer compared with that in N. In OMI-II, however, it was significantly shorter than in N. The prolongation of IIA-MVO time reflected impaired LV relaxation accompanied by LV dysfunction. The maintenance of low minimal LVP was the main contributor to the lengthening of MVO-O time in AP and OMI-I. Conversely, elevated minimal LVP and impaired LV relaxation resulted in the shortening of MVO-O time in OMI-II.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Pulmonary arterial pressure and plasma concentration of atrial natriuretic factor (ANF) in patients with heart disease.

To study the factors controlling the release of atrial natriuretic factor (ANF), we analyzed the peripheral plasma ANF concentration in 34 patients with heart disease who underwent cardiac catheterization. A significant positive correlation between plasma ANF concentration and pulmonary arterial pressure (systolic, r = 0.87; diastolic, r = 0.75; mean, r = 0.85; each p less than 0.001) was found in all the patients examined. There were significant positive correlations between plasma ANF concentration and systolic right ventricular pressure (r = 0.86, p less than 0.001), pulmonary capillary wedge pressure (r = 0.50, p less than 0.01) and mean right atrial pressure (r = 0.39, p less than 0.05). A weak but significant negative correlation was found between plasma ANF concentration and stroke volume index (r = -0.43, p less than 0.05). The correlation coefficient between plasma ANF concentration and mean pulmonary arterial pressure was significantly stronger than those between plasma ANF concentration and pulmonary capillary wedge pressure, and between plasma ANF concentration and mean right atrial pressure (p less than 0.05 and p less than 0.01, respectively). In 10 patients with mitral valvular disease, significant correlations with plasma ANF concentration were also found for pulmonary arterial pressure (systolic, r = 0.80; diastolic, r = 0.82; mean, r = 0.82; each p less than 0.01). These findings suggest that pulmonary arterial pressure may play an important role in the mechanism of release of ANF from atrial cardiocytes.

Adult↗
PubMed1986

Quantitative analysis of acute myocardial infarction using single photon emission computed tomography using technetium-99m pyrophosphate.

The usefulness of single photon emission computed tomography (SPECT) using technetium-99m pyrophosphate (99mTc-PPi) was evaluated in 15 patients with acute myocardial infarction. SPECT was performed with a rotating gamma camera after conventional planar images were made. Infarct size was measured from transaxial images of myocardial pyrophosphate uptakes. In each slice, the boundary was defined by subtracting 70 percent of the maximal counts and the number of voxels automatically counted. This subtraction rate was determined by phantom study and by comparing SPECT using 99mTc-PPi with thallium-201-gated myocardial scintigraphy (201Tl gated SPECT). The planar images showed diffuse uptakes in two of the 15 patients, and in these cases it was difficult to detect the infarct site. In contrast, SPECT images clearly imaged the infarct site consistent with the electrocardiographic findings, and they were definitely separated from the uptakes in the bones in all cases. Infarct size, ranging from 3.4 ml to 78.3 ml, correlated well with cumulative creatine kinase release (r = 0.84, p less than 0.01, y = 772x + 13900). Correlation of infarct size with peak serum creatine kinase level was also significant (r = 0.66, p less than 0.01, y = 10.6x + 693). In conclusion, SPECT with 99mTc-PPi is a useful means of investigating the spatial distribution of pyrophosphate uptake and of evaluating the size of myocardial infarction.

Aged↗