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Biomedical subjects

K Shimamoto

Publications and source records attributed to K Shimamoto.

At least 307 records · Page 17Linked to original sources
PubMed1989

Direct evidence for local generation and release of angiotensin II in human vascular tissue.

A direct measurement of both angiotensins I and II immunoreactive substances was made in the perfusate from isolated human umbilical vein perfused with Krebs-Ringer solution which was free of any component of the renin-angiotensin system. The identity of the immunoreactive peptides was confirmed as angiotensin I and angiotensin II by high-performance liquid chromatography in reference to standard compounds. The rate of release of angiotensins was 41.9 +/- 7.4 and 63.4 +/- 12.0 pg for angiotensins I and II, respectively, during the first perfusion period of 30 min, and it remained stable at least for 3 hours. Angiotensin-converting enzyme inhibitor captopril, added to the perfusion medium (10(-9) to 5 x 10(-6) M), suppressed immunoreactive angiotensin II release in a dose-dependent fashion; the maximal percent inhibition of angiotensin II release evoked by captopril (5 x 10(-6) M) was approximately 56%. These results taken together with the previous observations of presence of essential components of the renin-angiotensin system in vascular tissue provide direct evidence for local generation and subsequent release of angiotensin II in vascular beds of human beings.

Angiotensin I↗
PubMed1989

A conformationally restricted analogue of L-glutamate, the (2S,3R,4S) isomer of L-alpha-(carboxycyclopropyl)glycine, activates the NMDA-type receptor more markedly than NMDA in the isolated rat spinal cord.

Depolarizing actions of 4 conformationally restricted L-glutamate analogues, (2S,3S,4S) isomer (L-CCG-I), (2S,3R,4R) isomer (L-CCG-II), (2S,3S,4R) isomer (L-CCG-III) and (2S,3R,4S) isomer (L-CCG-IV) of L-alpha-(carboxycyclopropyl)-glycine (L-CCG), were investigated in the isolated rat spinal cord by extracellular recordings of potential changes of motoneurones from the ventral roots, in order to study the interaction between the conformation of glutamate and its receptor subtype. The order of the depolarizing activity was quisqualate greater than L-CCG-IV = kainate greater than NMDA greater than L-CCG-I greater than L-CCG-III greater than L-CCG-II. The depolarization caused by L-CCG-IV was effectively blocked by the NMDA antagonists and Mg2+ ions, while the L-CCG-I response was not affected by these blockers. These results suggest that the NMDA-type receptor is activated by a folded form of L-glutamate.

Action Potentials↗
PubMed1989

Physiological role of renal kallikrein-kinin system in human.

The physiological role of renal kallikrein-kinin system in human is discussed by the three following topics. Localization of each component of renal kallikrein-kinin system: Kallikrein is localized in the apical site of the distal tubular epithelial cells and collecting ducts by the immunostaining method. Following the stop-flow method in dog kidney, kallikrein and kinin are recognized in the distal tubules. Kininase I, II and neutral endopeptidase (enkephalinase) are localized not only in the proximal tubules, but also in the distal tubules. The localization of kininases is further confirmed by the stop-flow method pretreated with specific inhibitors for each of the kininases. Sodium metabolism and renal kallikrein-kinin system: In normal subjects, fractional excretions of sodium and inorganic phosphorus which reflect the total and proximal sodium reabsorption, show significantly positive correlations for both urinary kallikrein and kinin excretions. In the case of 0.9% saline infusion, the activity of renal kallikrein-kinin system is augmented following the infusion as shown in the increases of urinary kallikrein and kinin excretions and the decreases of urinary kininases excretions. Relation to other renal depressor systems: The close relations among renal dopamine, kallikrein-kinin and prostaglandin systems have been suggested by a dopamine infusion study. Dopamine may augment the activity of the renal kallikrein-kinin system through both the increases of renal prekallikrein synthesis and kallikrein specific activity. From these studies reported up to the present, it is suggested that the renal kallikrein-kinin system produced in the distal nephron in the kidney may play a role in the sodium metabolism with other renal depressor systems in addition to its own action.

Amino Acid Sequence↗
PubMed1989

The pathophysiological role of kinin and chemical mediators on experimental allergic rhinitis.

In order to clarify the pathophysiological role of the chemical mediators, the releases of kinins, histamine and leukotriene C4(LTC4) into the nasal cavity were measured following nasal allergic challenge in ovalbumin(OA)-sensitized guinea pigs, or following nasal stimulation with one of these chemical mediators in OA-non-sensitized animals. In sensitized animals, an increased vascular permeability of nasal mucosa was recognized immediately after antigenic stimulation and lasted for 60-90 minutes. Releases of kinins and LTC4 into the nasal lavage fluid augmented not only immediately after the antigenic challenge, but also during 60 to 90 minutes after the stimulation. Release of histamine into the nasal lavage fluid was observed only immediately after the antigenic stimulation. In non-sensitized guinea pigs, nasal stimulation with bradykinin accelerated nasal vascular permeability. Nasal stimulation with histamine or LTC4 resulted in increase of nasal vascular permeability and of kinins concentration in the nasal lavage fluid. These results suggest that kinins might be concerned with the immediate and later vascular permeability during the allergic response.

Animals↗
PubMed1989

Significance of kallikrein-kinin and renin-angiotensin systems in the hypotensive mechanism of angiotensin-I converting enzyme inhibitors in essential hypertensives.

This study was undertaken to further clarify the role of kallikrein-kinin and renin-angiotensin systems in the hypotensive mechanisms of the angiotensin-I converting enzyme inhibitor by using highly sensitive and specific radioimmunoassays in patients with essential hypertension. Captopril was administered for 14 days (chronic effect), and the acute effects of captopril, alacepril and ramipril were also studied in the in-patients with essential hypertension. All of these converting enzyme inhibitors rapidly decreased the blood pressure and plasma angiotensin II levels, and increased plasma and urinary kinin and plasma renin activity in the acute effect. Following the administration of captopril for 14 days, these decreases and increases were maintained. The change of blood pressure was significantly correlated negatively with that of plasma kinin levels and positively with that of plasma angiotensin II levels in both the acute and chronic effect of converting enzyme inhibitors. Urine volume and urinary sodium excretion were markedly augmented, while both the change of urine volume and that of urinary sodium excretion were negatively correlated with the change of blood pressure in the chronic effect. These findings suggest that the hypotensive effect of converting enzyme inhibitors might be caused by an increase of plasma kinin and a decrease of plasma angiotensin II, and in part by an augmentation of urine volume and urinary sodium excretion. In this drug treatment, the renal kallikrein-kinin system may also play some role in the increase of urine volume and urinary sodium excretion through the increased kinin in the kidney.

Angiotensin II↗
PubMed1989

Relationship between human seminal kallikrein-kinin system and spermatogenesis.

The concentration of kallikrein and the activity of angiotensin converting enzyme (ACE) in the semen specimens mainly from patients with male sterility and from those who were subjected to vasoligation, and in the prostatic fluid specimens from normal controls were determined by radioimmunoassay (RIA) and the modified Cushman's method, respectively. The kallikrein level in the semen from normal control was 40.4 +/- 21.3 ng/ml which was more than 10 times that in the blood. The value tended to increase with the decrease of the number of sperm. But there was no significant correlation between the kallikrein level and the sperm motility. The seminal kallikrein level from the patients subjected to vasoligation and that in the prostatic fluid from the normal male were 20-28 ng/ml. Therefore, that amount was considered to be secreted from the prostate gland. The results of column chromatography suggested that kallikrein combined with the other substances to form a high molecular compound in the semen. The ACE activity was 94.9 +/- 10.9 nmol/ml/min in the semen from the normal control, which was about three times that in the blood. Similar to kallikrein, it tended to decrease with the increase of the number of vasoligation and that in the prostatic fluid from the normal males was higher than that in the semen from the normal control and patients with male sterility, it was estimated that the considerable amount of ACE was secreted from the prostate gland.

Humans↗
PubMed1989

The renal kallikrein-kinin system in renoparenchymal hypertension.

In order to investigate the pathophysiological role of renal kallikrein (KK)-kinin system in renoparenchymal hypertension (RHT), urinary excretion of KK was measured in 15 patients with RHT and compared with that in 16 normotensive subjects (NT). The urinary kininase excretion was also determined in some subjects. KK quantity and activity was measured by direct radioimmunoassay and kininogenase assay, respectively. Kininase activity was determined as a bradykinin-degradating activity. The urinary excretion of KK quantity and activity as well as the fractional excretion of KK were significantly lower in RHT than in NT. Significantly positive correlations were observed between urinary excretion of KK quantity or KK activity and creatinine clearance. The fractional excretion of kininase was significantly higher in RHT than in NT while no significant difference was found in the urinary kininase excretion between these groups. These results suggest that renal KK-kinin system is suppressed not only in the whole kidney but in each nephrone which is still functioning, and the suppression of this system may contribute to the pathophysiology of RHT.

Adult↗
PubMed1989

Renal kininases in primary aldosteronism.

In order to further clarify the role of renal kallikrein-kinin (K-K) system in primary aldosteronism (PA), daily urinary excretions of renal K-K system components including kallikrein (KAL), kinin (KIN), total kininase (K-ase), K-ase I, K-ase II and neutral endopeptidase (NEP) were measured in PA and normotensives (NT). In this study, a new method for the simultaneous determination of human urinary K-ase I, II and NEP was established and employed. The daily excretions of KAL was significantly higher in PA than that in NT, while no difference was found in KIN between PA and NT. On the other hand, total K-ase in PA (897 +/- 258 micrograms/min/day) was significantly higher than that in NT (209 +/- 6). NEP was also significantly higher in PA (262 +/- 22 micrograms/min/day) than that in NT (127 +/- 6), whereas there were no differences in K-ase I and K-ase II between PA and NT. The relative contributions of K-ase I, II and NEP to total K-ase in NT were 14, 27 and 59%, while those in PA were 12, 17 and 36%, respectively. As a result, these three K-ase contributed only 64% to the total K-ase in PA. These findings suggested that 1) NEP may play a major role in the catabolism of renal KIN in human, 2) NEP is accelerated in PA, 3) unknown K-ase, different from K-ase I, II or NEP, may exist in PA, and 4) accelerated renal K-ase activity may play some role on the disorder of renal water-sodium metabolism and high blood pressure in PA.

Humans↗
PubMed1989

Localization of kallikrein in human male genital organ.

Male genital organs (testis, epididymis, seminal vesicle and vas deferens) were stained by the peroxidase-antiperoxidase (PAP) method to clarify the localization of kallikrein. Sertoli cells of the testis, epithelial cells of the epididymis, and adenocytes of the prostate gland were specifically stained showing that endogenous kallikrein was localized in these cells.

Epididymis↗
PubMed1989

A sensitive method for differential determination of kininase I, II and neutral endopeptidase (NEP) in human urine.

In order to clarify the significance of NEP in human renal kallikrein-kinin system, an assay system was developed for the simultaneous determination of kininase I, II and NEP activities in human. Each kininase activity was determined by measuring the hydrolysis of bradykinin in the presence of specific inhibitors of kininase I (2-mercaptomethyl-3-guanidinoethylthiopropanoic acid), kininase II (captopril) and NEP (phosphoramidon) in 8 normal subjects. The effects of the different assay buffers on kininase activities were also investigated by using a phosphate buffer. Total kininase, kininase I, II and NEP activities were 499 +/- 65 ng/min/ml (mean +/- S.E.), 55 +/- 8, 141 +/- 21 and 299 +/- 42, respectively in our method using a tris buffer, while a phosphate buffer brought about activities of 358 +/- 43, 45 +/- 5, 156 +/- 21 and 135 +/- 25 ng/min/ml. The relative contributions of kininase I, II and NEP to total kininase activity were 11, 29 and 59% in our assay system, while they were 13, 44 and 35% when a phosphate buffer was used. From these results it was suggested that 1) phosphate may inhibit urinary NEP activity, so that a tris buffer should be used as the incubation buffer, 2) NEP is the major component of human urinary kininases, and 3) NEP may play an important role in the renal kallikrein-kinin system.

Buffers↗
PubMed1989

Localization of neutral endopeptidase in the kidney determined by the stop-flow method.

Recently, the existence of neutral endopeptidase (NEP) as a new kininase in the kidney has been reported. In this study, the localization of NEP in the nephron was investigated and compared with other components of the renal kallikrein-kinin (K-K) system by using a stop-flow method in dog kidneys. The stop-flow method was performed according to the procedures previously reported by Scicli et al and Malvin et al. Five mongrel dogs (weighing 15-20 kg) were used in this study. Kininase I, II and NEP were measured by the modified procedure of Ura et al. Kallikrein and kinin were found in the distal tubules, and kininase I and II were observed in both the distal and proximal tubules. NEP was localized mainly in the proximal tubules. A small peak was also recognized in the distal tubules. From these results, it was suggested that, not only kininase I and II but also NEP existing in the proximal tubules may destroy kinin filtered from the glomeruli, and these kininases existing in the distal tubules may play an important role in connection with kinin producing enzymes on the regulation of activity in the renal kallikrein-kinin system.

Animals↗
PubMed1989

Alterations in cerebrospinal fluid angiotensin II by sodium intake in patients with essential hypertension.

1. Angiotensin (ANG) levels were measured in the cerebrospinal fluid of 15 patients with essential hypertension on a high sodium diet for 1 week and on a low sodium diet for a further week. ANGs were determined using a system of extraction by Sep-Pak cartridges followed by h.p.l.c. combined with radioimmunoassay. 2. Sodium depletion resulted in increases of ANG II in the cerebrospinal fluid from 1.16 +/- 0.38 (SEM) to 1.83 +/- 0.43 fmol/ml (P less than 0.01) and of ANG III from 0.65 +/- 0.11 to 0.86 +/- 0.15 fmol/ml (P less than 0.01). 3. The ANG II level in the cerebrospinal fluid was found to be unchanged and recovery of added ANG II was approximately 90%, even after incubation for 3 h, on both diets. Thus, it is unlikely that ANG II is produced or degraded in the cerebrospinal fluid in vitro. 4. There was no significant correlation between the cerebrospinal fluid and the plasma ANG II concentration on the low sodium diet. 5. These results suggest that the cerebrospinal fluid ANG II level increases with sodium depletion, and that the effect of the level of ANG II on the activity of the angiotensin-forming system in the central nervous system may be assessed by determination of ANG II in the cerebrospinal fluid in patients with essential hypertension.

Adult↗
PubMed1989

Role of kallikrein-kinin system in the hypotensive mechanisms of converting enzyme inhibitors in essential hypertension.

Patients with essential hypertension were studied to clarify the role of the kallikrein-kinin system in the hypotensive actions of angiotensin I converting enzyme inhibitors. Captopril, alacepril, ramipril, and altiopril administered in single doses rapidly decreased blood pressure and plasma angiotensin II levels, and increased plasma and urinary kinins as well as plasma renin activity. Following administration of captopril for 14 days, similar effects were observed. Urine volume and urinary sodium excretion were augmented after acute and chronic administration of captopril. The patients who received ramipril and altiopril were divided into renin subgroups. In the normal-renin group, the change in blood pressure was accompanied by an increase in plasma kinin level and a decrease in plasma angiotensin II level. However, in the low-renin group, although these drugs reduced blood pressure and increased plasma kinin, no significant change was observed in plasma angiotensin II levels. These findings suggest that (a) in patients with normal renin activity, the hypotensive effect of converting enzyme inhibitors might be caused by an increase in plasma kinin and a decrease in plasma angiotensin II, but in the low-renin group, the increase in plasma kinin levels may be more important; and (b) the augmentation of urine volume and urinary sodium excretion may also be related to the hypotensive effects of the converting enzyme inhibitors during long-term administration.

Adult↗
PubMed1989

Potent NMDA-like actions and potentiation of glutamate responses by conformational variants of a glutamate analogue in the rat spinal cord.

1. Neuropharmacological actions of all possible-state isomers of alpha-(carboxycyclopropyl)glycine (CCG), conformationally restricted analogues of glutamate, were examined for electrophysiological effects in the isolated spinal cord of the newborn rat. 2. Eight CCG stereoisomers demonstrated a large variety of depolarizing activities. Among them, the (2R, 3S, 4S) isomers of CCG (D-CCG-II) showed the most potent depolarizing activity, followed by the (2S, 3R, 4S) isomer (L-CCG-IV). 3. The depolarization evoked by L-CCG-IV, D-CCG-II and other D-CCG isomers was effectively depressed by N-methyl-D-aspartate (NMDA) antagonists. D-CCG-II was about 5 times more potent than NMDA in causing a depolarization. 4. The (2S, 3S, 4S) isomer of CCG (L-CCG-I) was more potent than L-glutamate in causing a depolarization of spinal motoneurones. The depolarization was slightly depressed by NMDA antagonists, but residual amplitudes of responses to L-CCG-I in the presence of NMDA antagonists We almost insensitive to 6,7-dinitro-quinoxaline-2,3-dione (DNQX) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), suggesting that L-CCG-I might be a novel potent agonist. 5. After application of the (2S, 3S, 4R) isomer of CCG (L-CCG-III), responses to L-glutamate, D- and L-aspartate were markedly enhanced. The enhancement lasted for a period of several hours without a further application of L-CCG-III. 6. L-CCG-III also caused a depolarization, but it seemed unlikely that the potentiation of the glutamate response was directly related to the depolarization evoked by L-CCG-III. 7. The potentiation might be due to inhibition of uptake processes, but L-CCG-III was superior to L-(-)-threo-3-hydroxyaspartate, a potent uptake inhibitor of L-glutamate and L-aspartate, in enhancing the response to L-glutamate in terms of amplitude and duration of responses. 8. CCG isomers should provide useful pharmacological tools for analysis of glutamate neurotransmitter systems.

Amino Acids, Dicarboxylic↗
PubMed1989

Epidemiological observation of coxsackieviruses group B in sewage.

Different types of coxsackieviruses group B were isolated from the sewage consecutively annually from January 1982 to March 1987: type 3 in 1982, type 4 in 1983, type 2, 4 and 5 in 1984, type 3 in 1985, and type 4 in 1986 were found. These viruses caused large epidemics among children aged 1 to 4 and proximities. Herald waves for the epidemics were observed six times during this period, and the viruses were detected in a brief period of isolation. With respect to the periodicity of these viruses, the cycles for types 3 and 4 were 2 to 3 years, and longer cycles seemed to be exhibited by types 1, 2, and 5. The onset and termination of the epidemics will only be grasped by surveys throughout the year. HEp-2 cells exhibited the best sensitivity to the viruses.

Adolescent↗
PubMed1989

Renin inhibitor and converting enzyme inhibitors suppress vascular angiotensin II.

The direct effects of a renin inhibitor, N-acetyl-pepstatin and five angiotensin converting enzyme inhibitors, captopril and the active diacid forms of enalapril, ramipril, cilazapril, and CS-622, on the vascular renin-angiotensin system were examined in isolated perfused rat mesenteric arteries. Vascular renin activity and angiotensin II (Ang II) released into the perfusate were determined. Infusion of N-acetyl-pepstatin (5 X 10(-8)-5 X 10(-6) M) suppressed vascular renin activity and Ang II release dose dependently. Isoproterenol (10(-6) M) induced a 135 +/- 30% increase in Ang II release from the basal value. N-Acetyl-pepstatin (5 X 10(-6) M) suppressed isoproterenol-induced Ang II release. Infusions of 5 X 10(-6) M captopril and the diacid forms of enalapril, ramipril, cilazapril, and CS-622 by themselves had little effect on Ang II release, but concomitant infusion of isoproterenol with these angiotensin converting enzyme inhibitors significantly decreased Ang II release (71 +/- 21%, 51 +/- 40%, 8 +/- 21%, 69 +/- 24%, and 44 +/- 29% increase, respectively, from the basal values). These results indicate that N-acetyl-pepstatin suppresses the vascular renin-angiotensin system. This effect may in part contribute to the hypotensive actions of renin inhibitors. Although angiotensin converting enzyme inhibitors also suppress locally generated Ang II, the mechanism and physiological significance still remain to be clarified.

Angiotensin II↗