SHIMIZU, T., NUNOKI, K. and TAIRA, N. Characterization of Neuronaland Vascular Histamine Receptors Mediating the Salivary and VasodilatorResponses to Histamine of the Dog Submandibular Gland. Tohoku J. exp. Med., 1981, 134 (1), 1-8-The submandibular gland in situ was perfused with blood through the glandular artery at constant pressure in anesthetized dogs, and all drugs were administered intra-arterially. During infusion of metiamide, histamine and 2-(2-pyridyl)ethylamine (PEA) produced salivary and vasodilator responses consisting of an early and a late component. The dose-response curves for respective components of the salivary and vasodilator responses to PEA were parallel with the corresponding curves for histamine and in producing these responses PEA was about 40 times less potent than histamine on a molar basis. During infusion of mepyramine, histamine and dimaprit produced only the early vasodilator response. The dose-vasodilator response curves to histamine and dimaprit were parallel, and dimaprit was about 750 times less potent than histamine on a molar basis. The present results support the conclusion obtained in a previous study that neuronal histamine receptors mediating the whole salivary and the late vasodilator response are exclusively of the H1-type and vascular histamine receptors mediating the early vasodilator response consist of both H1- and H2-type although the former is predominant.
OMATA, K., OTSUKA, Y., CHIBA, S., ITOH, T., GOTOH, T., IMAI, Y., SAKURAI, Y., SATOH, M., HARUYAMA, T., HIWATARI, M., SATOH, K., KAITOH, A., ABE, K. and YOSHINAGA, K. Indomethacin Does Not Attenuate the Hypotensive Effect ofCaptopril, a Converting Enzyme Inhibitor in Goldblatt Hypertensive Rats. Tohoku J. exp. Med., 1981, 134 (1), 9-19-Whether or not prostaglandins (PGs) have anything to do with the hypotensive effect of a converting enzyme inhibitor, Captopril (SQ 14, 225), was studied in two kidney one clip Goldblatt hypertensive rats. Four to 10 weeks after clipping the left renal artery of male Splague-Dawley rats, 50mg/kg of captopril (Group 1, n=7) or 12.5mg/kg of indomethacin (Group 2, n=7) were infused for 4hr under the conscious state. For the subsequent 4hr, both 50mg/kg of captopril and 12.5mg/kg of indomethacin were infused in both groups of rats. Mean blood pressure (MBP) was recorded continuously. Plasma renin activity (PRA) and urinary excretion rate of PGE (UPGE) were measured by radioimmunoassay. Urinary sodium (UNa) and potassium (UK) excretions were measured by a flame photometer. After captopril infusion the pressor response to the injection of 100ng of angiotensin I decreased from 29.1± 4.2 to 4.8±1.6mmHg, and that of angiotensin II increased from 35.9±3.6 to 75.0±5.1mmHg (p<0.01), while the response to norepinephrine did not change. Indomethacin did not affect these pressor responses. In the preinfusion period MBP, PRA or UPGE was not different significantly in the two groups of rats. The infusion of captopril decreased MBP from 202±11 to 119±7.5mmHg (p<0.01) in the first group of rats. After the additional infusion of indomethacin MBP further decreased to 100±12mmHg, depsite the significant decrease of UPGE from 915±34 to 109±28pg/hr (p<0.01), and PRA increased from 22.1±4.2 to 34.1±7.1ng/ml/hr. UNa did not change after captopril infusion but decreased significantly after indomethacin infusion from 49.0±5.0 to 22.8±3.5μEq/hr. In the second group captopril also decreased MBP from 187±7 to 119±15mmHg (p <0.01), and increased PRA from 24.1±6.1 to 43.3±6.9ng/ml/hr (p<0.01) despite the significant decrease of UPGE from 1219±294 to 413±101pg/hr by the pretreatment with indomethacin. UNa did not change in any period. The decrease of MBP was significantly correlated with the level of PRA prior to the infusion of captopril in both groups (r=-0.69, p<0.01). UK did not change significantly in any period in the two groups of rats. Our data that indomethacin did not attenuate the hypotensive effect of captopril indicate that PGs do not participate in the hypotensive effect of captopril and that the hypotensive effect of captopril is mainly due to the inhibition of renin-angiotensin system in two kidney one clip Goldblatt hypertensive rats.
ISEMURA, M., HANYU, T., ONO, T., IGARASHI, R., SATO, Y., GEJYO, F., NAKAZAWA, R., MIYAKAWA, T., TAKAGI, T., KUBOKI, Y., and SASAKI, S. Studieson Prolidase Deficiency with a Possible Defect in Collagen Metabolism. Tohoku J. exp. Med., 1981, 134 (1), 21-28-Skin collagen of a female patient with prolidase deficiency was examined for the distribution of borohydride-reducible cross-links and the proportion of type III to type I collagen. Patient's skin contained after reduction more dihydroxylysinonorleucine relative to hydroxylysinonorleucine and type III collagen than expected for normally matured skin. These findings suggest that collagen of the patient's skin failed to follow a time-related normal maturation process and that collagen metabolism was disturbed. The composition of urinary collagen metabolites was also unusual. On the other hand, her asymptomatic brother with prolidase deficiency showed the normal urinary composition of collagen metabolites. It is suggested that prolidase deficiency and defect in collagen metabolism independent of it are both responsible for clinical manifestation.
SEKINE, T., KAMEYAMA, J., SASAKI, I., LIN, J. and SATO, T. Influence ofPancreatic Duct Ligation on Gastric Acid Secretion. Tohoku J. exp. Med., 1981, 134 (1), 29-38-The influence of pancreatic duct ligation (PDL) on gastric secretion was investigated in dogs with a Heidenhain pouch. A test meal was given to the dogs before PDL, and following PDL the dogs were administered with the test meal mixed with pancreatic enzymes and with the test meal alone in succession. The responses to the test meal were examined in the control period and every one week for a period of 1 to 6 weeks following PDL to identify the changes in gastric acid secretion, serum gastrin levels, immunoreactive glucagon (IRG) levels and immunoreactive insulin (IRI) levels. Gastric acid secretion in response to food stimulations markedly increased after PDL. However, the acid secretion was significantly inhibited by the administration of pancreatic enzymes. Serum gastrin levels began to increase from the second week and continued to increase until the sixth week after PDL, revealing no effect of pancreatic enzymes. IRG levels also increased following PDL, particularly in cases administered with pancreatic enzymes. IRI levels were higher at the first week of PDL than before PDL, but tended to decrease thereafter. It is assumed that gastric hypersecretion after PDL would have complicated relations with IRG, gastric inhibitory polypeptide (GIP) as well as with antral gastrin.
WATANABE, S., OZEKI, T. and OSHIBA, S. Stomach Ulcer and LysosomalCathepsin. Tohoku J. exp. Med., 1981, 134 (1), 39-44 - Gastric ulcers were induced in rats by i.m. injections of vitamin A, and i.p. injection of histamine, or injections of both vitamin A and histamine. The incidence of ulcer formation was highest in the vitamin A-histamine group. However, ulcer formation also occurred after the administration of vitamin A alone as a lysosomal labilizer. Furthermore, the vitamin A-histamine group showed a remarkably elevated cathepsin activity in the tissue of gastric wall. In the experiments of ulcer formation by vitamin A injections, the specific activity and the enzyme release of cathespin were elevated already in the early stage after vitamin A administration. Consequently, cathepsin activity in stomach juice was remarkably elevated in the stage of the ulcer formation. In the clinic, the cathepsin activity in the mucous membrane of human gastric wall was remarkably high in the antrum and the angulus of the stomach, in which ulcer formation tends to occur most frequently. In view of these results, cathepsin in the stomach seems to play an important role in the formation of gastric ulcers.
MAEZAWA, S., OHIRA, S., SAKUMA, M., MATSUOKA, S., WAKUI, A. and SAITO, T. Effects of Inducer of Liver. Drug-Metabolizing Enzyme on Blood Level ofActive Metabolites of Cyclophosphamide in Rats and in Cancer Patients. Tohoku J. exp. Med., 1981, 134 (1), 45-53 - It was already reported that a masked compound, Cyclophosphamide (Endoxan, EX) undergoes the first-step metabolism by a drug-metabolizing enzyme in liver microsomes, cytochrome P-450. By pretreatment with phenobarbital as an Inducer of P-450, the maximum blood level of active metabolites of EX (normustard-like substances) in normal rats was 2.3 times higher than that in non-treated rats, in conformity with the increase in amount of liver P-450 and in alkylating activity of EX. In YS (Yoshida sarcoma)-bearing rats, the value of liver P-450 went down day by day to 1/2 on the 4th day after inoculation, but it remained normal when animals were pretreated with phenobarbital. In parallel with this, the blood level of normustard-like substances after EX administration was normal or showed a tendency toward increase. In 11 clinical cases pretreated with phenobarbital, the blood level of normustard-like substances 1 to 3hr after EX administration, at the time when it reaches the peak, was 1.5 times higher on an average than that in cases without pretreatment.
OYANAGI, K., SOGAWA, H., MINAMI, R., NAKAO, T., KARUBE, K, and TSUGAWA, S. A New Transport Interaction of Dibasic Amino Acids and Citrulline in HumanKidney. Tohoku J. exp. Med., 1981, 134 (1), 55-58 - The oral loading tests of lysine in 9 healthy men and the intravenous loading tests of lysine, ornithine and arginine in 3 healthy men were carried out. The results indicated that the membrane transport system of citrulline in the human kidney was clearly inhibited by dibasic amino acids, lysine, ornithine, and arginine.
ISAWA, T., TESHIMA, T., HIRANO, T., EBINA, A., SHIRAISHI, K. and KONNO, K. Effect of Isoproterenol on Regional Pulmonary Perfusion and Its Blockade byPropranolol. Tohoku J. exp. Med., 1981, 134 (1), 59-69 - Effects of isoproterenol and Propranolol on regional pulmonary perfusion were assessed in the dog. In each experiment the right upper lobe was isolated in vivo by a balloon catheter and artificially ventilated with nitrogen, air or 60% oxygen in nitrogen before and after administration of the medicaments listed above. The rest of the lungs kept breathing air spontaneously. Following administration of isoproterenol regional pulmonary perfusion increased in the hypoxic right upper lobe induced by artificial ventilation with nitrogen, but the increase was not observed when isoproterenol was administered following pretreatment with propranolol. Administration of propranolol alone did not induce any change in regional pulmonary perfusion distribution. When artificial ventilation was done in the right upper lobe either with air or 60% oxygen in nitrogen, thus inducing regional less hypoxia or hyperoxia, no change in regional perfusion was observed with any of the medicaments. Thus, isoproterenol reversed regional hypoxic pulmonary vasoconstriction, but its action was blocked by pretreatment with propranolol. Propranolol per se, however, showed no effect on pulmonary vascular responses to the different alveolar oxygen tensions.
ISAWA, T., TESHIMA, T., HIRANO, T., EBINA, A., SHIRAISHI, K., FUKUDA, Y. and KONNO, K. Effect of Dopamine on Regional Pulmonary Perfusion. Tohoku J. exp. Med., 1981, 134 (1), 71-77 - Dopamine effect on regional pulmonary perfusion in the right upper lobe was studied in 6 dogs in which the lobe was isolated by a balloon catheter and artificially ventilated with nitrogen, air or 60% oxygen in nitrogen, while the rest of the lungs was allowed spontaneous air respiration. Dopamine was administered at the rate of 20μg/kg/min. Each dog served as its own control. There was no change in the regional vascular responses to the different alveolar oxygen tensions in the right upper lobe before and after dopamine administration.
USUBUCHI, I., SATO, T. and KUDO, H. Significance of Sudan III Stainingin Macrophages. Tohoku J. exp. Med., 1981, 134 (1), 79-85 - Peritoneal macrophages of mice, 48hr after intraperitoneal administration of albumin (egg white), were studied. Almost all granules in the cytoplasm of macrophages stained by the supravital staining with neutral red were revealed to be colored brick red by the staining with Sudan III in the smear preparation. Because of lack of lipids in the inoculum, it is difficult to explain that these granules stained with Sudan III were lipids phagocytosed. The observation led the suggestion that the Sudan III stained granules in macrophages were out of all relation to lipids phagocytosed and that the granules indicated some functional phase of macrophages.
KIMURA, I., SATO, G. and ITAHARA, K. Delineation of Voluntary Movementin Parkinson's Disease with the Manual Control System. Tohoku J. exp. Med., 1981, 134 (1), 87-96 - An assessment of the dynamic characteristics of voluntary movement in 20 patients with Parkinson's disease and 20 normal subjects was performed by the manual control system. The following eight parameters were estimated and mapped on the plane with eight axes: gain constant between the input and the output, cut frequency for evaluation of the frequency response of human operator, dead time, square error, correlation coefficient, and three different points of coherency for the measurement of the linearity of human operation. In Parkinson's disease, we found a low gain constant of 8.34±9.64 dB (mean±S.D.) (26.5±2.12 in controls), a narrow cut frequency of 1.08±0.91 radians/sec (5.65±1.25), a long dead time of 0.79±0.27sec (0.19±0.05), a large square error, a law correlation coefficient, and low points of coherency. Among the eight parameters, the gain constant and the dead time proved to be the most useful for quantitative assessment of motor disability for this disorder. Our method promises to be valuable to confirm the effects of drug therapy and the progression of the disease.
GOTO, K. and TAMAHASHI, N. Electron Microscopic Studies on Cell-SizedBilayer Liposomes. Tohoku J. exp. Med., 1981, 134 (1), 97-102 - Cell-sized bilayer liposomes have been visualized directly in the electron microscope by a thin section method. Fixation in lanthanum nitrate plus potassium permanganate has made this visualization possible. Trilamellar images were seen in thin sections of the fixed liposomes; measurements made from microdensitometer tracings revealed a thickness (peak-to-peak distance) ranging from 25.3 to 55.3Å. The mean peak-to-peak distance of 35.6±8.2 (±S.D.) was in good agreement with the value obtained by Robertson from typical myelin figures.