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Biomedical subjects

M Asano

Publications and source records attributed to M Asano.

At least 415 records · Page 23Linked to original sources

Comparison of inhibitory effects of calcium channel blockers and that of a calmodulin antagonist in strips of mesenteric arteries from spontaneously hypertensive and normotensive rats.

Effects of calcium channel blockers and of calmodulin antagonist on the contractile responses to norepinephrine (NE) were compared between strips of mesenteric arteries from 6- and 14-week-old spontaneously hypertensive rats (SHR) and age-matched, normotensive Wistar-Kyoto rats (WKY). The ratio of the maximum contraction developed by NE to that by 60 mM KCl was significantly increased in strips from 14-week-old SHR. Niludipine, verapamil and diltiazem antagonized the maximum NE contraction to a greater extent in strips from 14-week-old SHR than in those from the WKY. However, the antagonism by niludipine of the KCl- or caffeine-induced contraction was not significantly different between the strips from 14-week-old SHR and those from WKY. In strips from 6-week-old rats, there was no difference in the antagonism by niludipine of the maximum NE contraction. On the other hand, the effect of W-7 on the maximum NE contraction was not significantly different between the strips from 14-week-old SHR and those from WKY. Schild plot analyses demonstrated that alpha 1-adrenoceptors were the same for the strips from SHR and WKY. These results suggest that the enhanced maximum NE contraction in the mesenteric artery from 14-week-old SHR reflects the increased transmembrane influx of calcium, and the activity of calmodulin seems to be the same for the two strains.

Adrenergic alpha-Antagonists↗

Intravital-microscopic observations on the intravascular behavior of blood cell components during dietary-induced hyperlipidemia in the male rabbit.

In normal male rabbits loaded dietary cholesterol, intravital-microscopy revealed a marked acceleration of intravascular adhesiveness of white blood cells and aggregability of red blood cells and a swarming of lipid-laden macrophages in connective tissue space concurrently with a systemic hyperlipidemia and anemia. Possible roles of the microcirculatory changes in the atherogenesis were discussed.

Animals↗

New 1,4-dihydropyridines with vasoconstrictor action through activation of Ca++-channels.

We found four new phenylcarbamoyl-substituted 1,4-dihydropyridines which produced vasoconstrictor and vasopressor effects and we further investigated the mode of vasoconstrictor action of one of the derivatives, 2-(2-pyridil)ethyl-4-(2-chlorophenyl)-2,6-dimethyl-5-phenylcarbamo yl-1, 4-dihydropyridine-3-carboxylate (YC-170). In anesthetized dogs. YC-170 (0.1-3 mg/kg i.v.) produced dose-dependent increases in blood pressure, total peripheral resistance and maximum dLVP/dt with slight reductions of heart rate and aortic blood flow. Intracoronary injection of YC-170 (10-1000 micrograms) produced not only a decrease in coronary blood flow but also an immediate reversal of the coronary vasodilation induced by nicardipine (3 micrograms). YC-170 (0.1-3 mg/kg i.v.) also produced a dose-dependent and reversible vasopressor effect in both anesthetized and pithed rats. The vasopressor response to YC-170 in pithed rats was not attenuated by either hexamethonium, prazosin, yohimbine, ketanserin or reserpine but was antagonized by either nicardipine, nifedipine, verapamil or diltiazem. In isolated rabbit aorta, YC-170 (3 X 10(-6) to 3 X 10(-5) M) induced a dose-dependent and reversible contraction which was not affected by either phentolamine, prazosin, mepyramine, ketanserin or atropine but removed by either nicardipine, verapamil or a Ca++-free medium. YC-170 (1 X 10(-6) to 3 X 10(-5) M) displaced [3H]nitrendipine binding to the canine cardiac membrane in an apparently competitive manner with a Ki value of 1.7 X 10(-6) M. The results suggest that the new phenylcarbamoyl-substituted dihydropyridines, including YC-170, exert a direct vasoconstrictor effect, which appears to be associated with an influx of Ca++ through Ca++ channels.

Animals↗

Reduced function of the stimulatory GTP-binding protein in beta adrenoceptor-adenylate cyclase system of femoral arteries isolated from spontaneously hypertensive rats.

Arterial relaxant responses to beta adrenoceptor agonists are decreased in spontaneously hypertensive rats (SHR) when compared with normotensive Wistar-Kyoto rats (WKY). To determine which component of the beta adrenoceptor-adenylate cyclase (AC) system is involved in the decreased beta adrenoceptor responses, effects of two activators of AC-forskolin and cholera toxin and of dibutyryl cyclic AMP (DBcAMP) were compared between the strips of femoral arteries isolated from 13-week-old SHR and age-matched WKY. Arterial relaxant responses to either forskolin, an activator of AC or DBcAMP were not significantly different between the SHR and WKY, whereas the relaxant responses to norepinephrine (NE) via beta adrenoceptors were significantly weaker in the SHR than in the WKY. In the absence of timolol, a beta adrenoceptor antagonist, contractile responses to NE were significantly greater in the SHR than in the WKY. Timolol augmented the contractile responses to NE to a greater extent in the WKY than in the SHR. After the blockade by timolol of beta adrenoceptors, contractile responses to alpha adrenoceptor stimulation with NE were not significantly different between the two strains. The pretreatment of the strips with cholera toxin, an activator of stimulatory GTP-binding protein (Gs), antagonized the alpha adrenoceptor-mediated contractions much greater in the WKY than in the SHR. The alpha adrenoceptor-mediated contractions after the pretreatment with cholera toxin were comparable to the contractile responses to NE determined in the absence of timolol in either the SHR or the WKY. Forskolin and DBcAMP also antagonized the alpha adrenoceptor-mediated contractions. However, these antagonisms were not significantly different between the two strains. The cellular cAMP content in arterial strips after the stimulation with NE was significantly less in the SHR than in the WKY, whereas the cAMP contents were similar in arterial strips from both strains which were stimulated with forskolin. These results suggest that the reduced function of Gs is involved in the abnormality of beta adrenoceptor-AC system in the SHR femoral artery.

1-Methyl-3-isobutylxanthine↗

[Clinical experience with single and multiple subcutaneous administration of LHRH analog Buserelin (Hoe 766) in prostatic carcinoma: endocrinological study of optimum subcutaneous doses].

Seventy three patients with prostatic carcinoma (PC) and 7 patients with benign prostatic hypertrophy (BPH) in 12 institutes subcutaneously received single and multiple doses of Hoe 766, and clinical efficacy, safety and endocrine effects of drug were examined. In a single doses study, six doses were subcutaneously administered to 7 BPH and 3 with PC. Gonadotropin and testosterone levels in the blood were increased following all these doses. In a multiple study, 7 kinds of doses were given to 40 patients with PC. The optimum doses of subcutaneous injection was decided to be 500 x 3 micrograms/day based on gonadotropin and testosterone suppression. Objective response by NPCP's criteria was observed in 35.3% (complete response 5.9%, partial response 29.4%) following 3 months of Hoe 766 treatment. Adverse reactions were observed in 9 cases (12.8%): Treatment was discontinued in 3 cases (eruption in 2, nausea and vomiting in 1), and continued in 6 cases (8.6%) without any treatment required. Buserelin was thus considered to be an effective, safe drug to treat prostatic carcinoma.

Aged↗

Conjugation-dependent recovery of the Na+ pump in a mutant of Vibrio alginolyticus lacking three subunits of the Na+ pump.

The Na+ pump-deficient mutant, Nap1, of Vibrio alginolyticus was found to lack three subunits of Na+-dependent NADH:quinone oxidoreductase complex. Although a spontaneous Na+ pump positive revertant did not appear from Nap1, transconjugants that recovered both the Na+ pump activity and the subunits were isolated from Nap1 conjugated with the wild type. Moreover, the wild type was found to contain two different sizes of plasmids. These results suggest the possibility that the Na+ pump is encoded by a plasmid.

Biological Transport, Active↗

Release of endogenous gamma-aminobutyric acid from vocalization nucleus, the robust nucleus of the archistriatum of zebra finch in vitro.

The release of gamma-aminobutyric acid (GABA) from the robust nucleus of the archistriatum (RA) of the zebra finch was examined in slice preparations. Potassium-induced depolarization caused calcium-dependent release of GABA. GABA release by veratrine was blocked by tetrodotoxin. Electrical stimulation of fibers dorsal to RA also released GABA. There was no sex difference in GABA release per wet weight of RA, while the size of the female RA is smaller than that of the male RA.

Animals↗

Induction of histidine decarboxylase by dexamethasone in mastocytoma P-815 cells.

Dexamethasone at a concentration as low as 10 nM significantly increased both the histamine content and histidine decarboxylase activity of cultured mastocytoma P-815 cells. Both effects were clearly seen using several glucocorticoids, which were as effective as dexamethasone. In contrast to that of histamine, the serotonin level of mastocytoma P-815 cells was decreased by treatment with dexamethasone. The dexamethasone-induced increases in histamine content and histidine decarboxylase activity were completely suppressed by the addition of cycloheximide and actinomycin D. Mastocytoma P-815 cells were found to possess binding sites for [3H]dexamethasone in the cytosol (Kd = 15.7 nM) and the nuclei (Kd = 1.26 nM). These results show that glucocorticoids significantly stimulate de novo synthesis of histidine decarboxylase.

Animals↗

Diminished beta-adrenoceptor-mediated relaxation of arteries from spontaneously hypertensive rats before and during development of hypertension.

beta-Adrenoceptor agonists and other drugs were studied for their relaxant effects on femoral and mesenteric arterial strips from spontaneously hypertensive rats (SHR). The potency and efficacy of isoproterenol (ISO) in these arteries were decreased in SHR before and during the development of hypertension as compared with age-matched Wistar Kyoto rats (WKY). Reserpine and 6-hydroxydopamine inhibited the development of hypertension but did not alter the reduced ISO-induced relaxation of the arteries. These arteries from prehypertensive SHR (PHSHR) were less sensitive to salbutamol and cyclic AMP and cyclic GMP derivatives than arteries from age-matched WKY. The relaxation response to nitroprusside was less in the femoral but not in the mesenteric arteries from PHSHR than in arteries from age-matched WKY. The relaxation response to papaverine was not diminished in the PHSHR arteries. It was found that the SHR arteries had a reduced responsiveness to the beta-adrenoceptor agonists before the initiation of hypertension and that the diminished relaxation was not specific to the beta-agonists, although there was no generalized defect in vasorelaxation in PHSHR.

Albuterol↗

Positive and negative ion mass spectrometry of benzophenones, the acid-hydrolysis products of benzodiazepines.

Positive electron impact (EI), positive chemical ionization (CI), and negative CI mass spectra of 14 benzophenones are presented. In the positive EI mode, intense molecular peaks appeared for most compounds; some other peaks due to splitting at both sides of the carbonyl group also appeared. In the positive CI mode, [M + 1]+ quasi-molecular ions together with [M + C2H5]+ peaks were observed for all compounds; some fragment peaks were common to those in the positive EI mode. In the negative CI mode, the spectra were much simpler than those in the positive EI or CI mode. In the 1 Torr negative CI mode, some spectra showed only single molecular anions; in the 0.01 Torr negative CI mode, halogen or nitro peaks appeared in addition to the molecular anions. An extraction procedure for benzophenones from human urine and plasma after heating in strong acid, and their separation by gas chromatography (GC) are also presented to serve for their actual identification by GC/mass spectrometry.

Benzophenones↗

Studies of the slow releasing of testosterone from radiation-polymerized testicular prostheses implanted subcutaneously in the back of castrated rabbits.

A controlled release testicular prosthesis containing testosterone, which was previously dissolved in 2-hydroxyethyl methacrylate (HEMA) at a temperature of 80 degrees C, was prepared by radiation-induced polymerization in the supercooled state at a low temperature. The daily dose of testosterone released in vitro from the poly(HEMA) testicular prosthesis was kept constant at a rate of 5.5 +/- 1.5 mg/d throughout an experimental period of 900 d. In the in vivo experiments, the poly(HEMA) testicular prosthesis was implanted subcutaneously in the back of castrated rabbits over a maximum period of 11 mnth. The cumulative amounts of testosterone released in vitro and in vivo from the poly(HEMA) testicular prosthesis for a period of 11 mnth were found to be 2.1 g (30.0 wt% of initial drug) and 0.9 g (12.8 wt% of initial drug), respectively. The serum testosterone level in castrated rabbits with a poly(HEMA) testicular prosthesis rapidly decreased for periods up to 2 mnth (after increasing during the first 2 wk), then showed a moderate decrease for a few months, and finally held constant at a level of 10 ng/ml throughout the experimental period. It was concluded that a slight amount of testosterone is continuously released in vivo from the radiation-polymerized poly(HEMA) testicular prosthesis over a long period analogous with that in vitro.

Animals↗

Sensitivity to electricity in the catfish, Parasilurus asotus.

The Japanese catfish (Parasilurus asotus) responded in its respiratory reflex to weak electric field not less sensitively than Gymnarchus niloticus. A sensitivity peak was found at about 1-30 Hz. The threshold voltage gradient of the electroreceptive system was determined to be about 0.05 microV/cm. High sensitivity to electric field fluctuating in low frequency being common to Siluriformes, the role of the sensory systems may be common beyond the difference of habitats among species.

Animals↗

Vasodilator effects of cepharanthine, a biscoclaurine alkaloid, on cutaneous microcirculation in the rabbit.

Cutaneous microcirculatory responses to intravenous administration of cepharanthine (CT), a biscoclaurine alkaloid, isolated from Stephania cepharantha, were studied in a transparent round chamber installed in a rabbit ear, under conscious conditions. Vital-microscopic observations were made visually with a microscope-closed TV system and microphotoelectric plethysmography. Following the CT administration in doses of 1.0 and 3.0 mg/kg, an enhancement of rhythmic perfusion of microvascular blood due to vasomotion was developed for a period of 1 h or longer, although no appreciable change was observed following CT administration at 10.0 mg/kg. The microvascular dilator effect of CT appeared to have no direct association with systemic hemodynamics, based on the additional measurements of heart rate, blood pressure, carotid blood flow and auricular arterial blood flow.

Alkaloids↗

Enhancement of testicular cysteine proteinase inhibitor level in vitamin E-deficient rats.

The effect of vitamin E deficiency on levels of proteinase inhibitors in sex glands of male rats was studied. Inhibitor levels against cysteine proteinases, such as ficin and cathepsin H, and against serine proteinase such as trypsin were examined. Vitamin E deficiency for 4 mo after weaning induced a fivefold increase in cysteine proteinase inhibitor level in testis, a two- to fourfold increase in prostate and epididymis and no change in seminal vesicle. No appreciable change was observed in trypsin inhibitor level in testis, epididymis or seminal vesicle. Therefore, vitamin E deficiency was reflected most sensitively by the cysteine proteinase inhibitor level in testis. These observations agree with our previous findings that alpha-cysteine proteinase inhibitors in serum increased greatly whereas trypsin inhibitor in serum did not change in vitamin E-deficient rats. Major histological changes were observed in the testes of rats fed a vitamin E-deficient diet for 4 mo, although testis weight was not significantly affected by vitamin E deficiency.

Animals↗

Cysteine proteinase inhibitors in human and rat male sex glands.

The testis and prostate of men had two types of cysteine proteinase inhibitors of different isoelectric point (pI = 4.5 and 6.3) and molecular masses (90,000 and 12,000). The seminal vesicle contained not only these two inhibitors but also a basic inhibitor with a pI = 9.5 and Mr 11,000. In rats, the inhibitors in the testis and prostate consisted of two types with pI values of 4.3 and 4.8 and Mr 90,000 for both. In addition to these two inhibitors, the seminal vesicle contained large amounts of two basic inhibitors with pI values of 7.5 and 8.3 and Mr of 11,000 for both. We suggest that the basic cysteine proteinase inhibitor found in semen might be excreted from or be modified in the seminal vesicle.

Animals↗

Effects of acupuncture needle application upon cutaneous microcirculation of rabbit ear lobe.

Microcirculatory effects of the application of an acupuncture needle (32-gauge, silver) to the back, corresponding to Geshu (B17) in human beings, were studied in vivo by microscope, using a transparent ear chamber in conscious rabbits. Although no striking findings were obtained during the needle application for a period of 30 minutes, it was clearly observed that the microvascular blood flow increases gradually in parallel with augmenting spontaneous rhythmic fluctuation of the vessel diameter, namely vasomotion, throughout a continuous observation period longer than 2 hours following release from the needle application. Diameters of arterioles and venules at the full-dilating phases of vasomotion reached levels higher than 200% and 250% of the initial values just before application of the needle, respectively. The clinical efficacy of acupuncture was suggested to be explained at least in part by the increased rhythmic microvascular blood flow in parallel with vasomotion, from the physiological point of view based on the previous investigations.

Acupuncture Therapy↗