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Biomedical subjects

H Ono

Publications and source records attributed to H Ono.

At least 505 records · Page 28Linked to original sources

Role of Ca channel in the renal autoregulatory vascular response analysed by the use of BAY K 8644.

The role of Ca channel and extracellular Ca2+ on autoregulation of renal blood flow was investigated in the perfused kidney of the anesthetized dog. The perfusion pressure was changed in the range between 60 and 200 mm Hg. Intra-arterial infusion of nifedipine (5 micrograms/min) increased renal blood flow at a perfusion pressure above 100 mm Hg and inhibited autoregulation. Simultaneous infusion of 5 micrograms/min of BAY K 8644 antagonized the effect of nifedipine. Renal blood flow was increased and autoregulatory relationship between flow and perfusion pressure was inhibited by EDTA (30 mg/min) infusion. The inhibitory effect of EDTA on renal autoregulation was counteracted by simultaneous infusion of CaCl2 at 30 mg/min, but not counteracted by that of BAY K 8644 (5 micrograms/min). BAY K 8644 also could not antagonize the inhibitory effect of a vasodilator, papaverine (5 mg/min) on renal blood flow autoregulation. These results provide the evidence that the renal autoregulation involves the process of Ca2+ influx into the vascular smooth muscle cell through the Ca channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Pharmacological properties of N-methoxy-3-(3,5-ditert-butyl-4-hydroxybenzylidene)-2-pyrrolidone (E-5110), a novel nonsteroidal antiinflammatory agent.

The antiinflammatory activity of a novel pyrrolidone derivative E-5110 was investigated using anti-inflammatory, analgesic and antipyretic animal models in comparison to indomethacin (IND) and piroxicam (PIR). The acute antiinflammatory activity of E-5110 on carrageenin paw edema was similar to IND, and half of PIR. E-5110 inhibited the pleural exudate volume and leucocyte infiltration in a reversed passive Arthus reaction more potent than IND. The chronic inflammatory responses in the established adjuvant- and type II collagen-induced arthritis were suppressed by E-5110 similar to IND and PIR. The analgesic potency of E-5110 was similar to IND and PIR, but the antipyretic activity of E-5110 was more potent than that of IND, and slightly more potent than that of PIR. The ulcerogenic effect of E-5110 on rat gastric mucosa was less than that of the reference drugs.

Animals↗

5-Hydroxytryptamine agonistic action of methysergide and the absence of supersensitivity to 5-HT agonists in spinal flexor reflexes in rats.

The intravenous administration of L-5-hydroxytryptophan (5-HTP), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), p-chloroamphetamine (PCA), LSD and methysergide to acute spinal rats, transected at C1, stimulated the flexor reflexes induced by electrical stimulation applied to the skin of the toe. The enhancement produced by 5-HTP, 5-MeODMT and PCA, was not antagonized by the prior administration of a dose of LSD or methysergide, although the enhancement produced by 5-MeODMT, LSD and methysergide, but not that produced by 5-HTP and PCA, was antagonized by cyproheptadine. In rats treated with 5,6-dihydroxytryptamine (intracisternal administration, 2 weeks previously) supersensitivity was observed to the effects of 5-HTP, a precursor of 5-HT, while subsensitivity was observed for the effects of PCA, a releaser of 5-HT. However, no supersensitivity was observed for the effects of 5-MeODMT, LSD and methysergide. These results suggest that methysergide may have an agonistic action on the 5-HT receptors in spinal cord and that supersensitivity to 5-HTP in rats treated with 5,6-dihydroxytryptamine was due to the lack of uptake of 5-HT into terminals of descending 5-HT fibres or to the change in 5-HT receptors which were not sensitive to 5-MeODMT, LSD, methysergide or cyproheptadine.

5,6-Dihydroxytryptamine↗

Involvement of noradrenergic systems in the effects of conditioning stimulation of the lower brain stem on the lumbar spinal reflex in rats.

The effects of conditioning stimulation at various positions in the pons and the medulla on the lumbar spinal monosynaptic reflex (MSR) were examined in rats. The conditioning stimulation facilitated the MSR. Facilitation with long latency was completely blocked by phenoxybenzamine, chlorpromazine or haloperidol. Phenoxybenzamine and chlorpromazine inhibited the MSR. Haloperidol, on the other hand, augmented the MSR, and this effect became more potent after the brain stem had been transected at the upper part of the medulla oblongata. These results suggest that pontine noradreneric systems have a facilitatory influence on the MSR via alpha-adrenoceptors, and that alpha-blockers exert an inhibitory effect on the MSR by blocking these receptors.

Adrenergic alpha-Antagonists↗

Rigidity in rats due to radio frequency decerebration and effects of chlorpromazine and mephenesin.

Bilateral radio frequency (RF) lesions of the midbrain were produced in an attempt to establish a non-bleeding method of producing decerebrate rigidity in rats. Marked extensor rigidity occurred with a high reproducibility in hindlimbs without the appearance of voluntary movement. Stretch reflex tension induced by repetitive dorsiflexion of the hindfeet was employed as a measure of the intensity of rigidity. Chlorpromazine-HCl (0.1-1 mg/kg, i.v.) and mephenesin (10-50 mg/kg, i.v.) which depress intercollicular decerebrate rigidity, reduced the RF decerebrate rigidity. These results suggest that RF decerebrate rigidity can be used instead of intercollicular transection rigidity in the pharmacological and physiological studies.

Animals↗

Effects of histamine on the guinea-pig stomach: excitation of smooth muscle and inhibition of transmitter release.

1 The effects of histamine on electrical responses of smooth muscle cells of the guinea-pig stomach were studied. 2 In the fundus, histamine (above 10(-6) M) depolarized the membrane and decreased the membrane resistance. In the antrum, the slow waves were enhanced by histamine, without change in the resting membrane potential or membrane resistance (10(-7)-10(-6) M), or with depolarization of the membrane (above 10(-5) M). 3 When the effects of histamine on neuromuscular transmission were estimated from changes in the amplitude of junction potentials, the amine (above 10(-7) M) inhibited the excitatory junction potential (e.j.p.) recorded in the fundus. Inhibitory junction potentials (i.j.p.) recorded in the antrum and atropine-treated fundus were also inhibited by histamine. 4 Repolarization of the histamine-induced depolarization to the resting potential level did not restore the amplitude of the e.j.p. to the control value. 5 These actions of histamine on the smooth muscle cells and on junction potentials were inhibited by either mepyramine or cimetidine, agents which block the H1- and H2-receptor, respectively. 6 It is concluded that in the guinea-pig stomach, histamine exerts a direct excitatory effect on the smooth muscle cells and has inhibitory actions on cholinergic excitatory and non-adrenergic, non-cholinergic inhibitory transmission.

Animals↗

Autoregulation of renal blood flow during the infusion of acetylcholine or carbachol in anaesthetized dogs.

Whether renal blood flow autoregulation is abolished by acetylcholine was re-examined by kidney perfusion experiments in anaesthetized dogs. Renal blood flow was dose-dependently increased by the renal arterial infusion of acetylcholine (2 and 5 micrograms min-1) or another muscarinic agent, carbachol (2 and 5 micrograms min-1) and was maintained at an increased level during the infusion. When perfusion pressure was changed stepwise between 60 and 200 mmHg, the infusion of acetylcholine or carbachol caused no impairment of autoregulation. It is concluded that autoregulation is independent of muscarinic stimulation of vascular smooth muscle in the kidney.

Acetylcholine↗

Incorporation into human enamel of fluoride slowly released from a sealant in vivo.

Fluoride incorporation into human enamel from an experimental sealant resin in vivo was investigated. The sealant consisted of a newly synthesized methacryloyl fluoride-methyl methacrylate (MF-MMA) copolymer resin, which contains acidic fluoride covalently bonded to carbonyl groups and releases fluoride ions slowly by hydrolysis in an aqueous environment. This experimental sealant was applied to the enamel of permanent pre-molars and the control sealant without MF-MMA copolymer to that of the contralateral teeth. Fluoride concentration was determined by an enamel biopsy procedure with acid-etching four weeks after the sealant application. As much as 3500 ppm fluoride was found to be deposited at 10 microns depth in the enamel under the MF-MMA copolymer sealant. The increase in fluoride concentration was significant even at 60 microns. Of the fluoride incorporated into the enamel, from 70 to 80% was present as a tightly bound form. This resin sealant is expected to protect the enamel from caries attack even after detachment of the sealant.

Boranes↗

Inhibitory effects of trifluoperazine and chlorpromazine, calmodulin inhibitor, on autoregulation of renal blood flow.

An intra-arterial infusion of a calmodulin inhibitor trifluoperazine (3 mg/min) or chlorpromazine (5 mg/min) caused obvious inhibition of autoregulation of renal blood flow in dogs. Simultaneous infusion of CaCl2 (30 mg/min) or Ca channel activator BAY K 8644 (5 micrograms/min) with these calmodulin inhibitors reduced renal blood flow, but could not block the inhibitory activity of calmodulin inhibitors on the autoregulation. The present experiment shows the contribution of the Ca-calmodulin system to the mechanism of autoregulation of renal blood flow.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Cardiovascular effects of paroxetine, a newly developed antidepressant, in anesthetized dogs in comparison with those of imipramine, amitriptyline and clomipramine.

The cardiovascular effects of various antidepressant drugs including paroxetine, imipramine, amitriptyline and clomipramine, administered intravenously, have been assessed. Paroxetine, imipramine, amitriptyline or clomipramine potentiated the response to norepinephrine (0.1 microgram/kg, i.v.) on systemic blood pressure, while paroxetine, imipramine and amitriptyline weakened the response to tyramine (30 micrograms/kg, i.v.). A marked decrease in systemic blood pressure was observed after large doses of each drug (3 and 10 mg/kg of paroxetine; 1-10 mg/kg of imipramine, amitriptyline or clomipramine); and half of the animals died following administration of 10 mg/kg of imipramine, amitriptyline or clomipramine. Paroxetine did not show a marked effect on heart rate at a dose of up to 3 mg/kg, although 0.1-3 mg/kg of imipramine, amitriptyline or clomipramine dose-dependently caused tachycardia. ECG disturbances were observed in animals administered 10 mg/kg of imipramine, amitriptyline or clomipramine; but in contrast, 10 mg/kg of paroxetine caused only slight changes in the ECG. Prolongation of atrio-ventricular conduction time was observed with all the drugs. It was concluded that the effects of paroxetine on the canine heart are more mild in comparison with other tricyclic antidepressants used, although its pharmacological features are essentially similar to those of other drugs.

Amitriptyline↗

Follicle culture enhances fertilizability and cleavage of bovine oocytes matured in vitro.

The fertilization and cleavage of bovine oocytes matured by intra- or extra-follicular methods were investigated. Oocytes were fertilized in vitro or in the rabbit oviduct and cleavage was assessed after in vitro culture of in vitro fertilized oocytes and after in vivo culture (rabbit oviducts) of xenogenously fertilized oocytes. The effect of fertilization with fresh-diluted or frozen-thawed semen were also examined. The intra-follicular method did not increase the nuclear maturation rate as compared with the extra-follicular method (57.9 and 52.7%, respectively). However, the proportions of in vitro fertilized eggs (54.8%) and of cleaved eggs (two to eight cells; 34.6%) in the rabbit oviduct for 48 h after xenogenous fertilization were higher (P less than .025) in the intra-follicular oocytes than those of the extra-follicular oocytes (37.1 and 21.3%, respectively). It was also found that the use of fresh-diluted semen resulted in more cleaved eggs from the rabbit oviduct than the use of frozen-thawed semen (43.4 and 23.3% in the intra-follicular oocytes, P less than .025; 31.0 and 7.8% in the extra-follicular oocytes, P less than .05), while the appearance of cleaved eggs following in vitro fertilization was extremely low (0 to 6.6%). The present results demonstrated that the intra-follicular culture method of bovine oocytes provided a physiological environment for cytoplasmic maturation leading to higher fertilizability and development than the conventional in vitro culture of extra-follicular oocytes.

Animals↗

Comparison of the effects of the new anxiolytic suriclone and benzodiazepines on motor function and electroencephalogram.

(6-(7-Chloro-1,8-naphthyridin-2-yl)-7-oxo-2,3,6,7-tetrahydro-5H- 1,4- dithiino[2,3-c]pyrrol-5-yl)-4-methyl-1-piperazinecarboxylate (suriclone, RP 31264), a new anxiolytic, produced behavioral effects similar to those of diazepam and lorazepam, had a protective effect against electroshock convulsion and potentiated the sleeping effect of hexobarbital in mice. It inhibited crossed extensor reflexes in chicks and augmented the dorsal root reflex potential, the increase of which is considered to be an index of increased GABAergic presynaptic inhibition. Suriclone produced high-amplitude slow waves in the amygdala and cerebral cortex and desynchronization of theta waves in the hippocampus in rat electroencephalogram (EEG). These observations were quantitatively confirmed by power spectrum analysis of EEG. The mechanisms of action of suriclone on the CNS are discussed in relation to those of benzodiazepines.

Animals↗