75 results on '"Toda, N."'
Search Results
2. NEUROGENIC NITRIC OXIDE AND ACETYLCHOLINE IN THE REGULATION OF MONKEY CILIARY ARTERIAL TONE
- Author
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Okamura, T., primary, Toda, M., additional, Ayajiki, K., additional, and Toda, N., additional
- Published
- 1997
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3. Superoxide Anion Impairs Endothelium-Dependent Vascular Relaxation in Insulin Resistant Rat Aortas
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Shinozaki, K., primary, Kashiwagi, A., additional, Okamura, T., additional, Nishio, Y., additional, Hidaka, H., additional, Ayajiki, K., additional, Toda, N., additional, and Kikkawa, R., additional
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- 1997
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4. P-33 - INHIBITION BY HYPOXIA OF NITROXIDERGIC NERVE FUNCTION IN CANINE CEREBRAL ARTERIES
- Author
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Ayajiki, K., Okamura, T., Fujioka, H., and Toda, N.
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- 1997
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5. 35 - Superoxide Anion Impairs Endothelium-Dependent Vascular Relaxation in Insulin Resistant Rat Aortas
- Author
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Shinozaki, K., Kashiwagi, A., Okamura, T., Nishio, Y., Hidaka, H., Ayajiki, K., Toda, N., and Kikkawa, R.
- Published
- 1997
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- View/download PDF
6. 25 - NEUROGENIC NITRIC OXIDE AND ACETYLCHOLINE IN THE REGULATION OF MONKEY CILIARY ARTERIAL TONE
- Author
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Okamura, T., Toda, M., Ayajiki, K., and Toda, N.
- Published
- 1997
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- View/download PDF
7. Functional study on nitroxidergic nerve in isolated dog pulmonary arteries and veins.
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Ayajiki K, Okamura T, Noda K, and Toda N
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- Animals, Dogs, Hexamethonium pharmacology, In Vitro Techniques, Methylene Blue pharmacology, Muscle Relaxation drug effects, Nicotine pharmacology, Nitroarginine pharmacology, Pulmonary Artery physiology, Pulmonary Veins physiology, Nitrogen Oxides metabolism, Pulmonary Artery innervation, Pulmonary Veins innervation
- Abstract
In dog pulmonary arterial and venous strips without endothelium under treatment with prazosin, nicotine induced relaxation that was abolished by N(G)-nitro-L-arginine, hexamethonium and methylene blue. L-Arginine antagonized the N(G)-nitro-L-arginine action. Neurogenic relaxations tended to be more evident in the vein. Nitric oxide (NO)-induced relaxations were greater in the veins than in the arteries. Concentrations of NO to induce the same magnitude of relaxation as that to nicotine were higher in the arteries. In conclusion, dog pulmonary arteries and veins are innervated by nitroxidergic (nitrergic) nerves, and NO is released by nerve stimulation with nicotine in a larger amount in the artery than the vein.
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- 2002
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8. Neurogenic cerebral vasodilation mediated by nitric oxide.
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Okamura T, Ayajiki K, Fujioka H, Shinozaki K, and Toda N
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- Animals, Brain blood supply, Dogs, Enzyme Activation, Macaca physiology, Nitrergic Neurons enzymology, Cerebral Arteries innervation, Cerebral Arteries physiology, Cerebrovascular Circulation, Nitrergic Neurons physiology, Nitric Oxide metabolism, Vasodilation
- Abstract
In cerebral arteries isolated from most of mammals, nerve stimulation produces relaxations in contrast to contractions in peripheral arteries. The relaxant mechanism is found to be non-adrenergic and non-cholinergic, but the neurotransmitter is not clarified until recently. Based on several functional and histological studies with isolated cerebral arteries, nitric oxide (NO) is now considered to be a neurotransmitter of the vasodilator nerve and the nerve has been called a nitroxidergic (nitrergic) nerve. Upon neural excitation, calcium influxed through N-type Ca2+ channels activates neuronal NO synthase, and then NO is produced by the enzyme from L-arginine. The released NO activates soluble guanylate cyclase in smooth muscle cells, resulting in relaxation with a cyclic GMP-dependent mechanism. The functional role and neuronal pathway have also been investigated in anesthetized dogs and Japanese monkeys. The nitroxidergic (nitrergic) nerves innervating the circulus arteriosus, including the anterior and middle cerebral and posterior communicating arteries, are found to be postganglionic nerves originated from the ipsilateral pterygopalatine ganglion and tonically dilate cerebral arteries in the resting condition. Our findings suggest that the nitroxidergic (nitrergic) nerve plays a physiologically important role to maintain a steady blood supply to the brain.
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- 2002
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9. Functional studies on blockade by neosurugatoxin of nicotinic receptors in nitroxidergic and sensory nerve terminals and intramural ganglionic cells.
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Ayajiki K, Okamura T, Fujioka H, Nakayama K, Tsuji K, and Toda N
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- Animals, Arteries drug effects, Arteries innervation, Arteries physiology, Calcitonin Gene-Related Peptide pharmacology, Cerebral Arteries drug effects, Cerebral Arteries innervation, Cerebral Arteries physiology, Dogs, Dose-Response Relationship, Drug, Duodenum drug effects, Duodenum innervation, Duodenum physiology, Electric Stimulation, Enzyme Inhibitors pharmacology, Female, Ganglia cytology, Ganglia physiology, In Vitro Techniques, Male, Muscle Relaxation drug effects, Nicotine antagonists & inhibitors, Nicotine pharmacology, Nicotinic Agonists pharmacology, Nicotinic Antagonists pharmacology, Nitroarginine pharmacology, Presynaptic Terminals physiology, Skin blood supply, Skin drug effects, Skin innervation, Tetrodotoxin pharmacology, Vasodilation drug effects, Vasodilation physiology, Ganglia drug effects, Mollusk Venoms pharmacology, Nitric Oxide physiology, Presynaptic Terminals drug effects, Receptors, Nicotinic drug effects
- Abstract
In isolated canine cerebral and cutaneous arteries and duodenum, effects of neosurugatoxin (NSTX) on the response to nicotine were compared. Nicotine-induced relaxations are mediated by nitric oxide (NO) from vasodilator nerves in cerebral arteries and by calcitonin gene-related peptide (CGRP) in cutaneous arteries treated with NO synthase inhibitors. Duodenal relaxation to nicotine is mediated by NO from inhibitory nerves. Cerebral arterial strips without endothelium responded to nicotine with relaxations that were inhibited by NSTX (3 x 10(-10) to 3 x 10(-9) M) concentration-dependently. Relaxations to nicotine of duodenal strips were attenuated by NSTX and abolished by tetrodotoxin, whereas those induced by K+ and electrical stimulation were not influenced. In cutaneous arteries treated with N(G)-nitro-L-arginine, nicotine-induced relaxations were attenuated by NSTX as low as 10(-10) M, but unaffected by tetrodotoxin. The inhibitory potency of NSTX was in the order of cutaneous artery > duodenum > cerebral artery. It is concluded that NSTX selectively antagonizes actions on nicotinic receptors in nitroxidergic nerves of cerebral arteries, CGRP-mediated sensory nerves of cutaneous artery and ganglionic cells of the duodenum, but the affinity of this toxin to nicotinic receptors in sensory nerves is the highest.
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- 1998
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10. Cerebral vasodilators.
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Toda N and Okamura T
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- Animals, Humans, Brain blood supply, Cerebral Arteries drug effects, Cerebral Veins drug effects, Vasodilator Agents pharmacology
- Abstract
The vascular tone, vascular resistance and blood flow in the brain are regulated by neural and humoral factors in quite a different way from those of peripheral organs and tissues. In contrast to the dominant vasoconstrictor control in the periphery, the intracranial vascular tone is predominantly influenced by vasodilator mediators over vasoconstrictor ones. Recent studies have revealed that nitroxidergic vasodilator nerve and endothelium-derived hyperpolarizing factor (EDHF) or K+ channel opening substance appear to play important roles in the regulation of cerebral arterial and arteriolar tone in primate and subprimate mammals, in addition to the accepted information concerning the crucial contribution of endothelium-derived relaxing factor (EDRF) or nitric oxide (NO), polypeptides, prostanoids, etc. This article summarizes characteristic properties of vasodilator factors in controlling the cerebral arterial and arteriolar tone that undoubtedly contribute to circulatory homeostasis. The content includes vasodilator nerve, endogenous vasodilator substances, and vasodilator interventions such as hypoxia, hypercapnia and hyperosmolarity.
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- 1998
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11. Inhibition by adrenomedullin of the adrenergic neurogenic response in canine mesenteric arteries.
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Okamura T, Zhang JX, Kangawa K, and Toda N
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- Adrenomedullin, Animals, Calcitonin Gene-Related Peptide pharmacology, Dogs, Electric Stimulation, Female, Hypotension chemically induced, Male, Mesenteric Arteries metabolism, Miotics pharmacology, Muscle Contraction drug effects, Muscle Relaxation drug effects, Peptide Fragments pharmacology, Proteins pharmacology, Mesenteric Arteries drug effects, Muscle, Smooth, Vascular drug effects, Peptides pharmacology, Synaptic Transmission drug effects, Vasodilator Agents pharmacology
- Abstract
Adrenomedullin (AM) inhibited the pressor action caused by transmural electrical stimulation in perfused isolated canine mesenteric arteries. The inhibitory potency of AM was greater than that of calcitonin gene-related peptide (CGRP) or proadrenomedullin NH2-terminal 20 peptide (PAMP). [8-37]CGRP did not affect the inhibitory action of AM, but suppressed the CGRP-induced inhibition. It may be concluded that AM has an ability to inhibit adrenergic neuronal transmission without the mediation of CGRP1 receptors in the peripheral vasculature, and this inhibition partly participates in the potent hypotensive action of AM.
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- 1997
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12. beta1-Adrenoceptor-mediated relaxation by norepinephrine in dog hepatic arteries.
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Shiraishi S, Okamura T, and Toda N
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- Adrenergic alpha-Antagonists pharmacology, Animals, Dogs, Endothelium, Vascular physiology, Female, Hepatic Artery drug effects, In Vitro Techniques, Male, Muscle Contraction drug effects, Muscle Relaxation drug effects, Muscle Relaxation physiology, Muscle, Smooth, Vascular drug effects, Hepatic Artery physiology, Muscle, Smooth, Vascular physiology, Norepinephrine pharmacology, Receptors, Adrenergic, beta-1 physiology
- Abstract
Dog hepatic arterial strips treated with prazosin responded to norepinephrine with concentration-related, endothelium-independent relaxations, the maximal response being 81.7% of the papaverine-induced maximal relaxation that was markedly greater than that in renal arteries. The norepinephrine-induced relaxation in hepatic arteries was significantly attenuated by metoprolol but not influenced by butoxamine. Relaxant responses to norepinephrine of dog hepatic arteries appear to be mediated by the beta1-adrenoceptor subtype, like those of coronary arteries. Evidence for functioning of the beta1-subtype in hepatic arteries would contribute to the analysis of neural and hormonal regulation of blood flow in the liver.
- Published
- 1997
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13. Comparison of neurogenic contraction and relaxation in canine corpus cavernosum and penile artery and vein.
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Hayashida H, Fujimoto H, Yoshida K, Tomoyoshi T, Okamura T, and Toda N
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- Adrenergic alpha-Antagonists pharmacology, Analysis of Variance, Animals, Arteries drug effects, Arteries innervation, Dogs, Dose-Response Relationship, Drug, Electric Stimulation, Hexamethonium pharmacology, Male, Muscle, Smooth physiology, Neurons, Efferent physiology, Nicotine antagonists & inhibitors, Penile Erection drug effects, Penis innervation, Prazosin pharmacology, Veins drug effects, Veins innervation, Muscle Contraction drug effects, Muscle Relaxation drug effects, Muscle, Smooth drug effects, Neurons, Efferent drug effects, Nicotine pharmacology, Nicotinic Agonists pharmacology, Penis drug effects
- Abstract
Functional roles of autonomic efferent nerves were compared in the isolated canine corpus cavernosum, penile artery and penile vein that participate in the penile erection by changing blood distribution. Nicotine produced moderate contraction in the arterial strips, but only a slight or no contraction in the corpus and venous strips. The contraction was suppressed or reversed to a relaxation by prazosin. Under alpha 1-adrenoceptor blockade, relaxations induced by nicotine were in the order of the corpus > artery > > vein. The response was abolished by NG-nitro-L-arginine (L-NA) and restored by L-arginine. The responses to nicotine and exogenous nitric oxide (NO) were abolished by oxyhemoglobin. The relaxant response to transmural electrical stimulation at 5 Hz was greater in the corpus than venous strips treated with prazosin, and it was abolished by L-NA. Contractions caused by nicotine under treatment with L-NA were greater in the artery than in the vein and corpus. Histochemical studies demonstrated nerve fibers containing NO synthase and tyrosine hydroxylase immunoreactivity in the corpus cavernosum, artery and vein. It is concluded that the canine corpus cavernosum, penile artery and penile vein are innervated by adrenergic, vasoconstrictor and nitroxidergic, vasodilator nerves; neurogenic vasodilatation is predominant in the corpus muscle, whereas neurogenic vasoconstriction predominates in the artery. Such a different functioning of the nerves may be responsible for the penile erection.
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- 1996
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14. Nitric oxide-mediated neurogenic relaxation in monkey mesenteric veins.
- Author
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Okamura T, Uchiyama M, An J, and Toda N
- Subjects
- Animals, Dose-Response Relationship, Drug, Female, Macaca mulatta, Male, Nicotine pharmacology, Norepinephrine pharmacology, Prazosin pharmacology, Vasodilation, Mesenteric Veins drug effects, Muscle, Smooth, Vascular drug effects, Nitric Oxide pharmacology
- Abstract
The purpose of this investigation was to determine if neurally induced vasodilatation is mediated by nitric oxide (NO) in monkey mesenteric veins. Helical strips of the monkey mesenteric vein were exposed to the bathing media for isometric tension recording, and perivascular nerves were stimulated by nicotine. Nicotine produced a contraction, which was potentiated by treatment with NG-nitro-L-arginine, a NO synthase inhibitor, the effect being reversed by L-arginine. The nicotine-induced contraction was reversed to a relaxation by prazosin. The relaxation was abolished by the NO synthase inhibitor, and it was restored by L-arginine. D-Enantiomers were without effect. The response was not influenced by timolol and indomethacin, but was abolished by hexamethonium and oxyhemoglobin. There were perivascular nerve fibers containing NO synthase immunoreactivity in the monkey vein. Neurally induced venous relaxations appear to be mediated by NO from perivascular nerves, as seen in dog and monkey mesenteric arteries. It is concluded that monkey mesenteric veins are innervated by nitroxidergic and adrenergic nerves, which may balance the vascular tone.
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- 1995
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15. Differences in adrenergic nerve and receptor function in dog internal thoracic, coronary and mesenteric arteries.
- Author
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Shiraishi S, Okamura T, Mori A, and Toda N
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- Animals, Coronary Vessels drug effects, Coronary Vessels innervation, Dogs, Electric Stimulation, Female, Immunohistochemistry, In Vitro Techniques, Isometric Contraction drug effects, Male, Mesenteric Arteries drug effects, Mesenteric Arteries innervation, Muscle Contraction drug effects, Muscle Relaxation drug effects, Muscle, Smooth, Vascular physiology, Radioligand Assay, Receptors, Adrenergic drug effects, Receptors, Adrenergic, beta drug effects, Receptors, Adrenergic, beta physiology, Sympathetic Nervous System drug effects, Thoracic Arteries drug effects, Thoracic Arteries innervation, Tyrosine 3-Monooxygenase metabolism, Coronary Vessels physiology, Mesenteric Arteries physiology, Muscle, Smooth, Vascular innervation, Receptors, Adrenergic physiology, Sympathetic Nervous System physiology, Thoracic Arteries physiology
- Abstract
Isolated dog internal thoracic arteries (ITA) responded to norepinephrine and phenylephrine with concentration-related contractions, which were suppressed by prazosin, but not by yohimbine. Clonidine did not contract ITA. In coronary arterial strips, norepinephrine produced a relaxation. Isoproterenol relaxed coronary arterial strips contracted with serotonin but did not alter the tone of ITA. Forskolin and beraprost, an analog of prostaglandin I2, relaxed coronary and ITA strips to a similar extent. The beta-adrenoceptor density, assayed by [3H]dihydroalprenolol binding, was markedly less in ITA than in coronary arteries. Nicotine and transmural electrical stimulation did not alter the tension of ITA. Immunohistochemical study indicated that nerve fibers containing tyrosine hydroxylase immunoreactivity were markedly less in ITA than in coronary and mesenteric arteries. These results indicate that beta-adrenoceptor function and adrenergic innervation are considerably reduced in dog ITA. Norepinephrine-induced vasocontraction appears to be mediated by alpha 1-adrenoceptors in the arteries.
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- 1994
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16. Histological and functional studies on the nitroxidergic nerve innervating monkey cerebral, mesenteric and temporal arteries.
- Author
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Yoshida K, Okamura T, and Toda N
- Subjects
- Amino Acid Oxidoreductases metabolism, Analysis of Variance, Animals, Cerebral Arteries physiology, Electric Stimulation, Female, Immunohistochemistry, Macaca, Male, Mesenteric Arteries physiology, Nerve Fibers drug effects, Nerve Fibers metabolism, Nerve Fibers physiology, Nicotine pharmacology, Nitric Oxide Synthase, Temporal Arteries physiology, Vasodilation, Cerebral Arteries innervation, Mesenteric Arteries innervation, Nitric Oxide metabolism, Temporal Arteries innervation
- Abstract
Nitroxidergic nerves and their functional role were determined in a variety of monkey arteries. Nitric oxide synthase-immunoreactive nerve fibers innervating the monkey arterial wall were histochemically determined by the use of nitric oxide synthase antiserum. Thin nitric oxide synthase-immunoreactive fibers were consistently found in the outer media of monkey cerebral, mesenteric and temporal arteries, in addition to many thicker fibers and nerve bundles in the adventitia. In the monkey pterygopalatine ganglion, the immunoreactivity was clearly seen in nerve cells, bundles and fibers. Helical strips of monkey arteries were exposed to the bathing media for tension recordings and were stimulated by electrical square pulses. In helical strips of the cerebral artery denuded of the endothelium, transmural electrical stimulation produced relaxations that were abolished by tetrodotoxin or NG-nitro-L-arginine, a nitric oxide synthase inhibitor. In the monkey mesenteric and temporal arterial strips treated with alpha-adrenoceptor antagonists, the relaxation caused by electrical stimulation was also abolished by the nitric oxide synthase inhibitor, and it was restored by L-arginine. Nitroxidergic perivascular nerves, histologically demonstrated, appear to play an important role in dilating the monkey cerebral artery and in counteracting a vasoconstriction associated with noradrenergic nerve activation in the mesenteric and temporal arteries.
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- 1994
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17. KRI-1314: an orally effective inhibitor of human renin.
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Etoh Y, Miyazaki M, Saitoh H, and Toda N
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- Administration, Oral, Amino Acid Sequence, Animals, Dipeptides administration & dosage, Dogs, Dose-Response Relationship, Drug, Female, Guinea Pigs, Heart Rate drug effects, Humans, Injections, Intravenous, Macaca, Male, Molecular Sequence Data, Molecular Weight, Morpholines administration & dosage, Naphthalenes administration & dosage, Rabbits, Rats, Renin blood, Renin metabolism, Tissue Distribution, Blood Pressure drug effects, Dipeptides pharmacology, Morpholines pharmacology, Naphthalenes pharmacology, Renin antagonists & inhibitors
- Abstract
Biochemical and pharmacological properties of KRI-1314, a newly synthesized, low molecular weight (M.W.: 690) renin inhibitor, were investigated in vitro and in vivo. The novel amino acid norstatine, which is shorter in chain length than the well-known statine, was incorporated into KRI-1314 as a tetrahedral transition-state analogue for the Leu10-Val11 scissile peptide in the renin substrate. KRI-1314 more strongly inhibited plasma renins from primates than those from dogs, rabbits, guinea pigs and rats. KRI-1314 competitively inhibited highly-purified human renin with a Ki value of 9.9 x 10(-10) M. KRI-1314 strongly inhibited the tissue renin-like activities of various organs from Japanese monkeys, with IC50 values on the order of 10(-8) M. KRI-1314 was also very stable in various tissue homogenates from Japanese monkeys. Both intravenous (from 0.25 to 3 mg/kg) and oral (10 and 30 mg/kg) administration of KRI-1314 to anesthetized and conscious sodium-depleted Japanese monkeys, respectively, significantly lowered the blood pressure and plasma renin activity without affecting the heart rate. In Japanese monkeys, KRI-1314 was continuously detected in the plasma up to at least 7 hr after oral administration of 10 and 30 mg/kg. These results demonstrate that KRI-1314 is a highly potent, primate-selective and long-lasting oral renin inhibitor with a blood pressure lowering effect.
- Published
- 1993
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18. Comparison of endothelium-dependent responses of canine internal thoracic and coronary arteries.
- Author
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Shiraishi S, Mori A, and Toda N
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- Acetylcholine pharmacology, Adenosine Triphosphate pharmacology, Animals, Calcimycin pharmacology, Coronary Vessels drug effects, Dogs, Female, In Vitro Techniques, Male, Mammary Arteries drug effects, Nitric Oxide pharmacology, Substance P pharmacology, Coronary Vessels physiology, Endothelium, Vascular physiology, Mammary Arteries physiology, Vasodilation drug effects
- Abstract
The endothelium-dependency of vasodilator responses was compared in helical strips of canine internal thoracic (ITA) and coronary arteries partially contracted with serotonin. The addition of acetylcholine produced a concentration-related relaxation in ITA and coronary arterial strips with an intact endothelium. The relaxations were not influenced by indomethacin, but were markedly inhibited or abolished by methylene blue, NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor, and endothelial denudation. The responses to low concentrations of acetylcholine were significantly greater in ITA than in coronary arteries, whereas relaxations induced by substance P, Ca2+ ionophore (A23187) or NO in ITA were significantly less. The substance P-induced relaxation in ITA and coronary arteries was endothelium-dependent, and it was almost abolished by L-NA. Relaxations induced by ATP in ITA were abolished by endothelium denudation and treatment with L-NA. In the coronary arteries, relaxing responses were inhibited only partially by removal of endothelium and L-NA. Acetylcholine, ATP and substance P relax canine ITA possibly by a mediation of endothelium-derived NO, but not prostaglandin I2. Coronary arterial relaxations induced by ATP appear to be mediated by an indirect action via NO released from the endothelium, in addition to a direct action on the smooth muscle.
- Published
- 1993
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19. Involvement of nitric oxide in endothelium-dependent, phasic relaxation caused by histamine in monkey cerebral arteries.
- Author
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Ayajiki K, Okamura T, and Toda N
- Subjects
- Animals, Arginine analogs & derivatives, Arginine pharmacology, Basilar Artery drug effects, Cerebral Arteries drug effects, Chlorpheniramine pharmacology, Cimetidine pharmacology, Dinoprost pharmacology, Endothelium, Vascular drug effects, Female, In Vitro Techniques, Isometric Contraction drug effects, Macaca, Male, Muscle Relaxation drug effects, Muscle Relaxation physiology, Muscle, Smooth, Vascular drug effects, Nitroarginine, Norepinephrine pharmacology, Receptors, Histamine H1 drug effects, Cerebral Arteries physiology, Endothelium, Vascular physiology, Histamine pharmacology, Muscle, Smooth, Vascular physiology, Nitric Oxide metabolism
- Abstract
Monkey cerebral artery strips partially contracted with prostaglandin F2 alpha responded to histamine with biphasic patterns of relaxation. The delayed and sustained relaxation was suppressed by cimetidine, whereas the phasic response was abolished by treatment with chlorpheniramine and NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor. The inhibition by L-NA was reversed by L-arginine. D-NA was without effect. Endothelium denudation abolished the phasic relaxation. We hypothesized that endothelium-dependent, phasic relaxations caused by histamine are mediated by NO that is released by H1-receptor stimulation, whereas the sustained relaxation is associated with the activation of H2-receptors in the smooth muscle of monkey cerebral arteries.
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- 1992
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20. Suppression by NG-nitro-L-arginine of relaxations induced by non-adrenergic, non-cholinergic nerve stimulation in dog duodenal longitudinal muscle.
- Author
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Toda N, Tanobe Y, and Baba H
- Subjects
- Animals, Arginine pharmacology, Atropine pharmacology, Dogs, Duodenum, Electric Stimulation, Female, Isometric Contraction drug effects, Male, Muscle, Smooth physiology, Nitric Oxide antagonists & inhibitors, Nitroarginine, Tetrodotoxin pharmacology, Arginine analogs & derivatives, Muscle Relaxation drug effects, Muscle, Smooth drug effects
- Abstract
In dog duodenal longitudinal muscle strips, transmural electrical stimulation (10 Hz, 15 sec) elicited a transient contraction, which was abolished by tetrodotoxin and atropine but potentiated by treatment with NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthesis inhibitor. The potentiation was reversed by L-arginine but not by its D-enantiomer. Acetylcholine-induced contractions were not influenced by L-NA. After treatment with atropine, the electrical neural stimulation relaxed the muscle strips partially contracted with bradykinin, the relaxation being abolished by tetrodotoxin and suppressed by L-, but not D-, NA. L-arginine reversed the L-NA-induced inhibition. Oxyhemoglobin abolished the relaxation caused by nerve stimulation and NO. The neurally-induced relaxation was not attenuated by adrenoceptor antagonists and indomethacin. It is concluded that electrical stimulation of non-adrenergic, non-cholinergic nerves relaxes dog duodenal smooth muscle, due possibly to NO produced upon neural excitation, and potentiation by L-NA of the contractile response to cholinergic nerve stimulation, would be derived from elimination of the neurally-induced relaxation.
- Published
- 1991
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21. Different modulation by cyclooxygenase inhibitors of the response to angiotensin II in monkey arteries and veins.
- Author
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Yoshida K, Yamazaki M, and Toda N
- Subjects
- Animals, Arteries drug effects, Endothelium, Vascular drug effects, Female, In Vitro Techniques, Macaca, Male, Methacrylates pharmacology, Muscle Contraction drug effects, Thromboxane-A Synthase antagonists & inhibitors, Veins drug effects, Angiotensin II pharmacology, Cyclooxygenase Inhibitors, Muscle, Smooth, Vascular drug effects
- Abstract
In coronary, renal and femoral arteries and mesenteric veins isolated from Japanese monkeys, tachyphylaxis to angiotensin (ANG) II (10(-7) M)-induced contraction rapidly developed. Contractions caused by ANG II in coronary arteries were attenuated by treatment with indomethacin and aspirin and also by endothelium denudation. Indomethacin inhibited the response of the arteries with and without endothelium to a similar extent. OKY 046, a thromboxane A2 synthesis inhibitor, failed to inhibit the response. In contrast, contractions of renal arteries were potentiated and prolonged by the cyclooxygenase inhibitors. ANG II-induced contractions of mesenteric veins were prolonged but those of femoral arteries were not altered by indomethacin. It is concluded that ANG II contracts monkey coronary arteries, possibly due to the release of vasoconstrictor prostanoids but not thromboxane A2 from endothelial and subendothelial tissues and also due to its direct action on smooth muscle, whereas contractions of renal arteries and mesenteric veins are blunted by vasodilator prostanoids, possibly PGI2. Cyclooxygenase products even if released do not appear to regulate femoral artery contractions produced by ANG II.
- Published
- 1991
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22. Role of nitric oxide in non-adrenergic, non-cholinergic nerve-mediated relaxation in dog duodenal longitudinal muscle strips.
- Author
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Toda N, Baba H, and Okamura T
- Subjects
- Animals, Arginine analogs & derivatives, Arginine pharmacology, Dogs, Duodenum drug effects, Duodenum innervation, Electric Stimulation, In Vitro Techniques, Muscle Relaxation drug effects, Muscle, Smooth innervation, Nitric Oxide antagonists & inhibitors, Nitroarginine, Oxyhemoglobins pharmacology, Stereoisomerism, omega-N-Methylarginine, Autonomic Nervous System physiology, Muscle, Smooth drug effects, Nitric Oxide pharmacology
- Abstract
Transmural electrical stimulation caused a relaxation in the dog duodenal longitudinal muscle strips treated with atropine, phentolamine and propranolol, which was abolished by tetrodotoxin. The relaxation was suppressed by oxyhemoglobin and L-NG-nitro-arginine (L-NA), but not influenced by D-NA. Inhibition by L-NA was reversed by L-arginine, but not by D-arginine. The response to transmural electrical stimulation was similar to that caused by nitric oxide or nitroglycerin. Nitric oxide appears to participate importantly in non-adrenergic, non-cholinergic nerve-mediated relaxation.
- Published
- 1990
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23. Modification by L-NG-monomethyl arginine (L-NMMA) of the response to nerve stimulation in isolated dog mesenteric and cerebral arteries.
- Author
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Toda N and Okamura T
- Subjects
- Animals, Arginine pharmacology, Blood Pressure drug effects, Cerebral Arteries drug effects, Dinoprost pharmacology, Dogs, Electric Stimulation, In Vitro Techniques, Mesenteric Arteries drug effects, Muscle Contraction drug effects, Muscle, Smooth, Vascular physiology, omega-N-Methylarginine, Arginine analogs & derivatives, Muscle, Smooth, Vascular drug effects
- Abstract
Treatment with L-NG-monomethyl arginine (L-NMMA) increased the vasoconstriction induced by adrenergic nerve stimulation in perfused dog mesenteric artery segments and suppressed the relaxant response to transmural nerve stimulation in dog cerebral artery strips, the effects of L-NMMA being reversed by L-arginine. The observed changes in nerve function may be associated with the inhibition of synthesis of nitric oxide.
- Published
- 1990
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24. Participation of calcium and sodium ions in genesis of the chronotropic effect of norepinephrine in isolated rabbit sinoatrial nodes.
- Author
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Toda N
- Subjects
- Animals, Bucladesine pharmacology, Dose-Response Relationship, Drug, Female, In Vitro Techniques, Ions, Male, Manganese pharmacology, Membrane Potentials drug effects, Norepinephrine antagonists & inhibitors, Rabbits, Sinoatrial Node cytology, Stimulation, Chemical, Theophylline antagonists & inhibitors, Theophylline pharmacology, Verapamil pharmacology, Calcium physiology, Heart Rate drug effects, Norepinephrine pharmacology, Sinoatrial Node drug effects, Sodium physiology
- Published
- 1977
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25. Contractile responses of isolated dog mesenteric arteries to angiotensin I, II and III.
- Author
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Toda N, Hayashi S, and Miyazaki M
- Subjects
- Angiotensin I antagonists & inhibitors, Angiotensin II antagonists & inhibitors, Angiotensin III antagonists & inhibitors, Animals, Bradykinin pharmacology, Dogs, Dose-Response Relationship, Drug, Female, In Vitro Techniques, Male, Mesenteric Arteries, Saralasin pharmacology, Angiotensin I pharmacology, Angiotensin II analogs & derivatives, Angiotensin II pharmacology, Angiotensin III pharmacology, Angiotensins pharmacology, Muscle Contraction drug effects, Muscle, Smooth drug effects, Vasoconstrictor Agents
- Abstract
The addition of angiotensin (Ang-) I, II and III caused a dose-dependent contraction of helically cut strips of dog mesenteric arteries. Tachyphylaxis developed following repeated additions of angiotensins. Average median effective concentrations of Ang-I, II and III were 3.7, 0.8 and 2.5 X 10(-8) M, respectively. Contractile responses to the angiotensins were attenuated to a similar extent by Ang-II antagonists, Sar1 Ileu8 Ang-II and Sar1 Ala8 Ang-II, but were unaffected by phentolamine, methysergide and diphenhydramine. The response to Ang-I was significantly reduced by treatment with bradykinin-potentiator B, while the response to Ang-II was not influenced. It may be concluded that Ang-I, II and III produce contractions possibly by activation of same Ang-II receptors and that contractions induced by Ang-I are associated, to some extent, with a conversion to Ang-II in the arterial wall.
- Published
- 1978
- Full Text
- View/download PDF
26. Alpha adrenoceptor subtypes responsible for dopamine-induced mesenteric vein contraction.
- Author
-
Toda N, Miyazaki M, and Okamura T
- Subjects
- Animals, Dogs, Female, In Vitro Techniques, Male, Mesenteric Veins drug effects, Muscle Contraction drug effects, Norepinephrine pharmacology, Yohimbine pharmacology, Dopamine pharmacology, Muscle, Smooth, Vascular drug effects, Receptors, Adrenergic, alpha physiology
- Published
- 1984
- Full Text
- View/download PDF
27. Age-dependence of the chronotropic response to noradrenaline, acetylcholine and transmural stimulation in isolated rabbit atria.
- Author
-
Toda N, Fu WL, and Osumi Y
- Subjects
- Age Factors, Animals, Cocaine pharmacology, Electric Stimulation, Female, In Vitro Techniques, Male, Propranolol pharmacology, Rabbits, Stimulation, Chemical, Tetrodotoxin pharmacology, Tyramine pharmacology, Acetylcholine pharmacology, Atrial Function, Heart Rate drug effects, Norepinephrine pharmacology
- Abstract
The chonotropic response to noradrenaline, tyramine, acetylcholine and transmural electrical stimulation was compared in atria isolated from rabbits at different stages of developmental after birth (day 2 to day 210). Pacemaker rates understeady state conditions were related inversely to days after birth; the rate in atria from rabbits at day 2 was significantly greater than that at days 10-210. The rate of neonatal rabbit atria was not significantly reduced by propranolol and the positive chontropic response to noradrenaline was not significantly reduced by propranolol and the positive chronotropic response to noradrenaline was not significantly different in atria from ages of rabbits as far as threshold concentrations for inducing tachycardia and ED50's were concerned. The maximum rate induced by noradrenaline was higher in neonatal rabbit atria than in adult rabbit atria. The effect of tyramine was approx. the same regardless of age. Increase in the pacemaker rate induced by transmural neural stimulation varied directly with age. The negative chronotropic effect of acetylcholine was greater in neonatal than in adult rabbit atria; the ED50 in the former was significantly less than in the latter. Bradycardia induced by transmural stimulation of intracardiac cholinergic nerves was related directly to age. Tachycardia in the neonatal rabbit atria may be due to electrogenic characteristics of pacemaker cells which differ from those in adult rabbit atria. Our evidence strongly suggests that the adrenergic and cholinergic nerves innervating the S-A node develop at an early postnatal stage in the rabbit.
- Published
- 1976
- Full Text
- View/download PDF
28. Potentiation of the contractile response of isolated aortae to transmural stimulation by angiotensin.
- Author
-
Toda N
- Subjects
- Animals, Bretylium Compounds pharmacology, Calcium pharmacology, Cocaine pharmacology, Culture Techniques, Dose-Response Relationship, Drug, Drug Interactions, Electric Stimulation, Female, Magnesium pharmacology, Male, Muscle Contraction drug effects, Norepinephrine metabolism, Norepinephrine pharmacology, Rabbits, Stimulation, Chemical, Angiotensin II pharmacology, Aorta drug effects, Vasoconstrictor Agents
- Published
- 1973
- Full Text
- View/download PDF
29. Regional and species differences in the response of isolated arteries to angiotnesin II.
- Author
-
Toda N and Miyazaki M
- Subjects
- Animals, Cats, Cattle, Dogs, Humans, In Vitro Techniques, Organ Specificity, Rabbits, Species Specificity, Angiotensin II pharmacology, Arteries drug effects
- Published
- 1978
- Full Text
- View/download PDF
30. Responsiveness to vasoconstrictor and dilator agents of senescent beagle cerebral arteries.
- Author
-
Shimizu I, Miyazaki M, and Toda N
- Subjects
- Adenosine pharmacology, Animals, Dogs, Epoprostenol pharmacology, Female, Histamine pharmacology, In Vitro Techniques, Isoproterenol pharmacology, Male, Nicotine pharmacology, Serotonin pharmacology, Aging physiology, Basilar Artery drug effects, Cerebral Arteries drug effects, Vasoconstrictor Agents pharmacology, Vasodilator Agents pharmacology
- Abstract
With advancing age from 2 to 12 years, contractions of isolated beagle cerebral arteries mediated by histamine H1 and serotonin receptors increased, whereas those induced by noradrenaline and angiotensin II did not differ. Relaxations by vasodilator substances, such as prostaglandin (PG) I2, isoproterenol, adenosine and K+ (5 mM), and by stimulation of vasodilator nerves in the adult and senescent beagle arteries did not significantly differ.
- Published
- 1986
- Full Text
- View/download PDF
31. Prostaglandin F2 alpha-induced contraction in isolated dog cerebral, coronary and mesenteric arteries soaked in excess potassium.
- Author
-
Toda N and Onoue H
- Subjects
- Animals, Coronary Vessels physiology, Dogs, Female, In Vitro Techniques, Male, Mesenteric Arteries physiology, Cerebral Arteries drug effects, Cerebral Arteries physiology, Coronary Vessels drug effects, Dinoprost pharmacology, Mesenteric Arteries drug effects, Potassium pharmacology, Vasoconstriction
- Abstract
Concentration-response curve for prostaglandin (PG) F2 alpha in helical strips of dog cerebral, coronary and mesenteric arteries were compared in control media and in those in which all the NaCl was replaced with isomolar KCl. Contractile responses to PGF2 alpha in concentrations up to 2 x 10(-6) M in cerebral arteries, to 10(-5) M in coronary arteries and to 5 x 10(-7) M in mesenteric arteries were not attenuated by excess K+. Contractions caused by PGF2 alpha, at least at these concentrations or lower, may not be associated with membrane depolarization.
- Published
- 1988
- Full Text
- View/download PDF
32. Modification by cadmium ions of 45calcium uptake by isolated rabbit aortae.
- Author
-
Hattori K, Shimoura K, and Toda N
- Subjects
- Animals, Biological Transport, Female, In Vitro Techniques, Male, Muscle Contraction, Potassium pharmacology, Rabbits, Aorta, Thoracic physiology, Cadmium pharmacology, Calcium metabolism
- Abstract
Treatment with 0.5 mM Cd++ suppressed the K+ (30 mM)-stimulated uptake and influx of 45Ca and abolished the K+-induced contraction in helical strips of rabbit aortae. The rapid and slow efflux of 45Ca previously accumulated was not appreciably affected by Cd++. It is concluded that interference with the transmembrane influx of Ca++ is a major mechanism of Cd++ action.
- Published
- 1983
- Full Text
- View/download PDF
33. Hypotensive effect of SA446, an angiotensin converting enzyme inhibitor, in 2-kidney, 1-clip renal hypertensive and normotensive dogs.
- Author
-
Nishimura K, Miyazaki M, Okunishi H, and Toda N
- Subjects
- 3-Mercaptopropionic Acid analogs & derivatives, Angiotensin I antagonists & inhibitors, Angiotensin I blood, Animals, Captopril pharmacology, Dogs, Female, Male, Peptidyl-Dipeptidase A blood, Renin blood, Sulfhydryl Compounds, Thiazolidines, 3-Mercaptopropionic Acid pharmacology, Angiotensin-Converting Enzyme Inhibitors, Blood Pressure drug effects, Hypertension, Renal drug therapy, Renin-Angiotensin System drug effects
- Abstract
Hypotensive effects of SA446, an angiotensin converting enzyme (ACE) inhibitor, and effects on the renin-angiotensin system were evaluated in conscious normotensive and 2-kidney, 1-clip renal hypertensive dogs. SA446 (1 mg/kg, p.o.) remarkably inhibited the pressor response to angiotensin (Ang) I between 1 and 6 hr after the administration in normotensive dogs. SA446 significantly decreased blood pressure at 10 mg/kg, p.o., in normotensive dogs. During repeated administration of SA446 (100 mg/kg/day, p.o.) for 13 weeks, the blood pressure was lowered, and the pressor response to Ang I and plasma ACE activity were strongly inhibited. ACE activities in the aorta and kidney were also inhibited. Plasma renin activity and plasma Ang I concentration increased by repeated SA446 application, while plasma aldosterone concentration decreased. The hypotensive effect of SA446 (5 mg/kg, p.o.) was more potent in 2-kidney, 1-clip renal hypertensive dogs than in normotensive dogs. SA446 had longer inhibitory effects on the pressor response to Ang I and more potent hypotensive effects than captopril. The hypotension caused by SA446 appears to be associated mainly with an inhibition of ACE in plasma and also in the vascular wall.
- Published
- 1987
- Full Text
- View/download PDF
34. Proceedings: Role of Ca++ and Na+ in producing tachycardia.
- Author
-
Toda N
- Subjects
- Animals, Cations, Divalent, Cations, Monovalent, Heart Conduction System drug effects, In Vitro Techniques, Rabbits, Calcium physiology, Heart Rate drug effects, Sodium physiology
- Published
- 1974
35. Length-tension relationship in isolated canine cerebral arteries.
- Author
-
Toda N, Hayashi S, and Hatano Y
- Subjects
- Animals, Dogs, In Vitro Techniques, Muscle Contraction drug effects, Muscle, Smooth drug effects, Serotonin pharmacology, Cerebral Arteries physiology
- Published
- 1976
- Full Text
- View/download PDF
36. Effects of elcatonin on plasma and urine electrolytes in infant beagles.
- Author
-
Miyazaki M, Okunishi H, and Toda N
- Subjects
- Animals, Blood Pressure drug effects, Calcium blood, Calcium urine, Dogs, Glomerular Filtration Rate drug effects, Phosphorus blood, Phosphorus urine, Renal Circulation drug effects, Calcitonin pharmacology, Calcium metabolism, Phosphorus metabolism
- Abstract
The effects of elcatonin (ECT) on the renal hemodynamics and electrolyte levels in plasma and urine were investigated in anesthetized infant beagles (3 months old) and adult beagles (9-10 months old). Intravenous injections of 50 MRC U/kg ECT did not alter the systemic blood pressure, renal blood flow, glomerular filtration rate, and urine flow in intact puppies as well as in puppies and adult dogs subjected to extirpation of the thyroid and parathyroid glands (TPTX). One hundred and twenty min after ECT injection, the plasma calcium concentration decreased by 1.06 +/- 0.15 mEq/l in intact puppies and 0.94 +/- 0.10 mEq/l in TPTX puppies, but decreased only by 0.38 +/- 0.22 mEq/l in adult TPTX dogs. The urinary calcium excretion decreased in all the puppies. The plasma phosphorus concentration decreased by 1.02 +/- 0.10 mg/dl, and the phosphorus excretion rate increased 63.6 +/- 26.4% in intact puppies; whereas the plasma phosphorus and phosphorus excretion were not altered in TPTX puppies. Diuresis and natriuresis were not obtained. These data suggest that the acute hypocalcemic effect of ECT is dependent on age and is not associated with its action on kidneys.
- Published
- 1982
- Full Text
- View/download PDF
37. Different responses to prostaglandins E1 and E2 of isolated canine coronary arteries.
- Author
-
Toda N, Usui H, and Sakae K
- Subjects
- Animals, Dogs, Dose-Response Relationship, Drug, Muscle Contraction drug effects, Papaverine pharmacology, Potassium pharmacology, Coronary Vessels drug effects, Prostaglandins E pharmacology
- Published
- 1975
- Full Text
- View/download PDF
38. Effects of 5-hydroxyindoleacetic acid on isolated canine cerebral arteries.
- Author
-
Toda N, Hojo M, Sakae K, and Usui H
- Subjects
- Animals, Dogs, Dose-Response Relationship, Drug, In Vitro Techniques, Muscle Contraction drug effects, Serotonin pharmacology, Cerebral Arteries drug effects, Hydroxyindoleacetic Acid pharmacology
- Published
- 1974
- Full Text
- View/download PDF
39. Responses of isolated dog coronary arteries to tyramine.
- Author
-
Hayashi S and Toda N
- Subjects
- Animals, Cocaine pharmacology, Dinoprost, Dogs, Dose-Response Relationship, Drug, Female, In Vitro Techniques, Male, Norepinephrine metabolism, Norepinephrine pharmacology, Phentolamine pharmacology, Propranolol pharmacology, Prostaglandins F pharmacology, Sympathetic Nervous System metabolism, Tyramine antagonists & inhibitors, Vasoconstriction drug effects, Vasodilation drug effects, Coronary Vessels drug effects, Tyramine pharmacology
- Abstract
In isolated dog coronary arteries contracted with prostaglandin F2 alpha, tyramine in concentrations of 10(-6) and 5 x 10(-6) M caused relaxations, but it produced contractions at 2 x 10(-5) M or higher. The relaxant response to tyramine was attenuated, but the contractile response was enhanced at the second trial as compared with the responses at the first. Relaxations induced by low concentrations of tyramine were reversed to contractions by treatment with propranolol (10(-6) M) or sotalol (10(-5) M), and were abolished by cocaine (3 x 10(-6) M) or bretylium (2 x 10(-5) M). In coronary arteries isolated from reserpine (0.5 mg/kg)-pretreated dogs, tyramine produced only a contraction. Under resting conditions, contractions induced by tyramine (5 x 10(-6) to 2 x 10(-3) M) were potentiated by cocaine and propranolol, and were inhibited by phentolamine. Norepinephrine produced a dose-dependent relaxation in the arteries contracted with prostaglandin F2 alpha. In the presence of propranolol, the arteries under resting conditions were contracted by norepinephrine, the contraction being suppressed by treatment with phentolamine. It may be concluded that relaxations of dog coronary arteries induced by tyramine are mediated by liberation of norepinephrine from adrenergic nerves which stimulates beta-adrenoceptors in the smooth muscle. It seems likely that the tyramine (2 x 10(-5) M or higher)-induced contraction is not mediated by norepinephrine released, but it is partly due to a direct action on alpha-adrenoceptors.
- Published
- 1982
- Full Text
- View/download PDF
40. Functional and histological changes in mesenteric arteries and aortas from monkeys fed a high cholesterol diet.
- Author
-
Toda N, Miyazaki M, and Hazama F
- Subjects
- Animals, Aorta pathology, Arteriosclerosis pathology, Arteriosclerosis physiopathology, Female, Lipids blood, Macaca, Male, Mesenteric Arteries pathology, Vasodilation drug effects, Aorta metabolism, Arteriosclerosis metabolism, Cholesterol, Dietary adverse effects, Mesenteric Arteries metabolism
- Abstract
Treatment of Japanese monkeys for 8 months with a high fat, high cholesterol diet produced atherosclerotic lesions in the aorta and mesenteric arteries, such as fatty dots, streaks and plaques, intimal thickening with accumulation of spindle-shaped cells and macrophages and endothelial cell flattening. Contractile responses of mesenteric arteries from control and atherosclerotic monkeys to electrical stimulation of adrenergic nerves, norepinephrine and angiotensin II did not differ, whereas contractions caused by serotonin in the atherosclerotic monkey arteries were significantly greater. Ketanserin and cinanserin suppressed the serotonin-induced contraction. Relaxations caused by adenosine and K+ (5 mM) were moderately attenuated in atherosclerotic monkey mesenteric arteries, and those by acetylcholine were reduced only slightly or not affected in the arteries or aortas. Relaxations of control and atherosclerotic arteries in response to nitroglycerin, isoproterenol and prostaglandin I2 did not differ. The relaxant response to K+ was reversed to a contraction by ouabain. Acetylcholine-induced relaxations were dependent on the endothelium and suppressed by atropine. Diet-induced atherosclerosis appears to potentiate contractions mediated via serotonergic 5-HT2 receptors and to attenuate relaxations possibly caused by activation of the electrogenic Na+ pump in the smooth muscle cell membrane. Endothelium-dependent relaxations via muscarinic receptors would not evidently be affected in mesenteric arteries and aortas from atherosclerotic Japanese monkeys.
- Published
- 1988
- Full Text
- View/download PDF
41. Automaticity induced by Ca++ chelating agents in isolated rabbit left atria.
- Author
-
Toda N
- Subjects
- Action Potentials drug effects, Animals, Atropine pharmacology, Dose-Response Relationship, Drug, Electric Stimulation, Ethylene Glycols pharmacology, Female, In Vitro Techniques, Magnesium pharmacology, Male, Manganese pharmacology, Membrane Potentials drug effects, Microelectrodes, Rabbits, Reserpine pharmacology, Sodium metabolism, Spectrophotometry, Tetrodotoxin pharmacology, Tyramine pharmacology, Calcium metabolism, Chelating Agents pharmacology, Heart Atria drug effects
- Published
- 1974
- Full Text
- View/download PDF
42. Mechanisms of action of eperisone on isolated dog saphenous arteries and veins.
- Author
-
Inoue S, Bian K, Okamura T, Okunishi H, and Toda N
- Subjects
- Animals, Arteries drug effects, Aspirin pharmacology, Dogs, Drug Interactions, Electric Stimulation, Female, In Vitro Techniques, Indomethacin pharmacology, Isometric Contraction drug effects, Male, Muscle Relaxation drug effects, Muscles blood supply, Regional Blood Flow drug effects, Saphenous Vein drug effects, Propiophenones pharmacology, Vasodilator Agents pharmacology
- Abstract
Effects of eperisone, an antispasmodic in skeletal muscle, were investigated in helical strips of dog saphenous artery and vein. Eperisone relaxed saphenous arteries and veins previously contracted with norepinephrine, serotonin, acetylcholine, K+, or Ba2+; but in contrast, it produced contractions in the blood vessels contracted with prostaglandin (PG) F2 alpha. Treatment with eperisone attenuated the contractions induced by norepinephrine and serotonin in the arteries and those by clonidine and phenylephrine in the veins. Eperisone inhibited angiotensin II-induced relaxations, mediated possibly by endogenous PGI2, but did not alter relaxations caused by exogenous PGI2. Treatment with eperisone (10(-5) M) potentiated the contractile response to electrical stimulation of adrenergic nerves; the potentiating effect was suppressed by yohimbine. The eperisone-induced contraction in PGF2 alpha-contracted arteries was inhibited by treatment with indomethacin or aspirin, although cyclooxygenase activity was not inhibited by eperisone. These results may indicate that eperisone blocks postjunctional alpha 1- and alpha 2-adrenergic, muscarinic, serotonergic receptors and prejunctional alpha 2 adrenoceptors and reduces PGI2 synthesis via a mechanism other than cyclooxygenase inhibition.
- Published
- 1989
- Full Text
- View/download PDF
43. Vasodilator actions of flunarizine in isolated dog cerebral and extracerebral arteries.
- Author
-
Bian K and Toda N
- Subjects
- Animals, Arteries drug effects, Calcium pharmacology, Dinoprost pharmacology, Dogs, Dose-Response Relationship, Drug, Female, In Vitro Techniques, Male, Oxygen physiology, Potassium pharmacology, Cerebral Arteries drug effects, Flunarizine pharmacology, Vasodilation drug effects
- Abstract
Flunarizine relaxed isolated canine arteries precontracted with prostaglandin (PG) F2 alpha, epithio-methano-thromboxane A2 and K+; the relaxation was in the order of cerebral greater than renal greater than mesenteric = coronary arteries, when contracted with PGF2 alpha or the thromboxane A2 analogue. Flunarizine-induced relaxation was unaffected by treatment with atropine, propranolol, cimetidine, cimetidine, chlorpheniramine, aminophylline and indomethacin, and by removal of endothelium. Under normoxia, flunarizine attenuated contractions elicited by Ca2+ in the K+-stimulated cerebral and mesenteric arteries that had been previously exposed to Ca2+-free media to a greater extent than that in PGF 2 alpha-stimulated preparations. The Ca2+-induced contraction in cerebral arteries was more sensitive to flunarizine than that in mesenteric arteries. Contractions caused by PGF2 alpha in Ca2+-free media were not influenced by flunarizine. In cerebral and mesenteric arteries that had been previously exposed to Ca2+-free media and severe hypoxia and then stimulated by PGF2 alpha and Ca2+, reoxygenation produced a persistent contraction. Flunarizine suppressed the reoxygenation induced-contraction. It is concluded that flunarizine dilates cerebral arteries predominantly over the other arteries; the vasodilatation appears to derive from an interference with the transmembrane Ca2+ influx that occurs through a voltage-dependent process and, to a lesser extent, receptor-operated channels, but not with the Ca2+ release from stored sites. Contraction induced by reoxygenation is expected to be due mainly to the transmembrane influx of Ca2+, which is also suppressed by flunarizine.
- Published
- 1989
- Full Text
- View/download PDF
44. Influence of fentanyl on the chronotropic response of isolated rabbit atria to cholinergic and adrenergic stimulation.
- Author
-
Hatano Y and Toda N
- Subjects
- Acetylcholine pharmacology, Animals, Electric Stimulation, Female, In Vitro Techniques, Levallorphan pharmacology, Male, Morphine pharmacology, Myocardial Contraction drug effects, Naloxone pharmacology, Norepinephrine pharmacology, Rabbits, Fentanyl pharmacology, Heart Rate drug effects, Parasympathetic Nervous System physiology, Sympathetic Nervous System physiology
- Published
- 1978
- Full Text
- View/download PDF
45. The regional difference of relaxations induced by various vasodilators in isolated dog coronary and mesenteric arteries.
- Author
-
Miwa K and Toda N
- Subjects
- Adenosine pharmacology, Alprostadil pharmacology, Animals, Diltiazem pharmacology, Dogs, Epoprostenol pharmacology, Female, In Vitro Techniques, Male, Muscle Relaxation drug effects, Nitroglycerin pharmacology, Nitroprusside pharmacology, Thromboxane A2 pharmacology, Coronary Vessels drug effects, Mesenteric Arteries drug effects, Muscle, Smooth, Vascular drug effects, Vasodilator Agents pharmacology
- Abstract
Relaxant responses to vasodilators, including nitroglycerin, sodium nitroprusside, prostaglandin I2 sodium salt (PGI2), prostaglandin E1 (PGE1), diltiazem hydrochloride and adenosine, were compared in helical strips of dog coronary arteries of different sizes and in coronary and mesenteric arterial strips. The relaxant responses to nitroglycerin, sodium nitroprusside, diltiazem and adenosine were significantly greater in coronary arteries than in mesenteric arteries, whereas the responses to PGI2 and PGE1 in these arteries did not significantly differ. In coronary arteries of different sizes, the relaxation induced by nitroglycerin was in the order of large greater than medium greater than small-size, while in contrast, the relaxations by adenosine, PGI2 and PGE1 were greatest in the small-size arteries and least in the large-size arteries. The relaxant responses to sodium nitroprusside and diltiazem did not differ in the coronary arteries of different sizes. Nitroglycerin, sodium nitroprusside and diltiazem appear to dilate coronary arteries more predominantly than mesenteric arteries. The preferential dilator action of PGI2 and PGE1 on distal coronary arteries, like that of adenosine, may lead more blood to re-distribute to the non-ischemic region of the heart in anginal patients.
- Published
- 1985
- Full Text
- View/download PDF
46. Analysis of the contractile response to serotonin and tryptamine of isolated dog cerebral, femoral and mesenteric arteries.
- Author
-
Fu LH and Toda N
- Subjects
- 5-Hydroxytryptophan pharmacology, Animals, Cinanserin pharmacology, Dogs, Female, In Vitro Techniques, Male, Methysergide pharmacology, Phentolamine pharmacology, Serotonin Antagonists pharmacology, Tryptamines antagonists & inhibitors, Tryptophan pharmacology, Cerebral Arteries physiology, Femoral Artery physiology, Mesenteric Arteries physiology, Serotonin pharmacology, Tryptamines pharmacology, Vasoconstriction drug effects
- Abstract
In helically-cut strips of cerebral arteries isolated from dogs, serotonin, tryptamine, 5-hydroxytryptophan and tryptophan caused a dose-related contraction. The potency was in the order of serotonin greater than tryptamine much greater than 5-hydroxytryptophan = tryptophan. In femoral arterial strips, only serotonin and tryptamine produced contractions. In cerebral arteries, the dose-response curve for serotonin was shifted to the right and downward by treatment with cinanserin, whereas in femoral and mesenteric arteries, the curves were shifted to the right. The contractile response of cerebral arteries to tryptamine was attenuated by cinanserin in concentrations above 10(-7) M; however, 10(-5) M was required to significantly reduce the response of femoral arteries. Phentolamine reduced the contractile response of femoral arteries to tryptamine, but not the response of cerebral arteries. It may be concluded that the different antagonism of cinanserin against the serotonin action on cerebral and femoral arteries is due to the ability of high concentrations of serotonin to induce relaxations of cerebral but not femoral arteries or to the different nature of receptors. Tryptamine appears to elicit contractions of cerebral arteries via a stimulation of tryptamine receptors, but elicit those of femoral arteries via stimulation of both alpha-adrenergic and tryptamine receptors. Whether or not receptors for serotonin and tryptamine are the same was not determined.
- Published
- 1983
- Full Text
- View/download PDF
47. Vasodilator effect of indapamide in dog mesenteric vasculature.
- Author
-
Miyazaki M, Morishita S, and Toda N
- Subjects
- Animals, Dogs, Hydralazine pharmacology, In Vitro Techniques, Trichlormethiazide pharmacology, Diuretics pharmacology, Indapamide pharmacology, Muscle, Smooth, Vascular drug effects, Splanchnic Circulation drug effects, Vasodilator Agents
- Abstract
Effects of indapamide, trichlormethiazide and hydralazine on isolated, perfused dog mesenteric vasculature and helical strips of the dog mesenteric artery were compared. It appears that indapamide-induced hypotension is associated with a direct relaxant action on arterial and arteriolar smooth muscle, whereas hydralazine acts exclusively on resistance vessels.
- Published
- 1985
- Full Text
- View/download PDF
48. Proceedings: Influence of 5-hydroxykynurenamine, a new serotonin metabolite, on isolated cerebral arteries.
- Author
-
Toda N
- Subjects
- Amines antagonists & inhibitors, Amines pharmacology, Animals, Aorta drug effects, Dogs, In Vitro Techniques, Kynurenine antagonists & inhibitors, Rabbits, Receptors, Drug, Serotonin metabolism, Serotonin pharmacology, Serotonin Antagonists, Basilar Artery drug effects, Kynurenine pharmacology
- Published
- 1974
49. Modification of angiotensin II-induced relaxation by dipyridamole, phthalazinol and aspirin in isolated dog renal arteries.
- Author
-
Toda N and Yamamoto M
- Subjects
- Animals, Cyclooxygenase Inhibitors, Dogs, Epoprostenol pharmacology, Female, In Vitro Techniques, Indomethacin pharmacology, Male, Muscle Relaxation drug effects, Renal Artery drug effects, 3',5'-Cyclic-AMP Phosphodiesterases antagonists & inhibitors, Angiotensin II pharmacology, Aspirin pharmacology, Dipyridamole pharmacology, Muscle, Smooth, Vascular drug effects, Phthalazines pharmacology, Pyridazines pharmacology
- Abstract
Angiotensin (ANG) II-induced relaxations in isolated dog renal and cerebral arteries are postulated to be mediated by the release of prostaglandin (PG) I2 from the arterial wall. In helical strips of dog renal arteries treated with dipyridamole, relaxations induced by ANG II (10(-7) M) and exogenously applied PGI2 (10(-8) M) were potentiated; the potentiation was appreciably greater in the ANG-induced relaxation. Treatment with phthalazinol did not alter the response to ANG II, but significantly potentiated the relaxation induced by PGI2. The ANG-induced relaxations were suppressed or reversed to contractions by aspirin or indomethacin. Combined treatment of dipyridamole with aspirin or indomethacin restored the relaxant response to ANG II, while phthalazinol in combination with aspirin did not restore the response. It may be concluded that the potentiation of responses to ANG II by dipyridamole is associated with increments in the release of PGI2 from the arterial wall and potentiations of the response of arterial smooth muscle to PGI2. Dipyridamole appears to increase the production of PGI2 even in the presence of PG synthesis inhibition by aspirin or indomethacin.
- Published
- 1983
- Full Text
- View/download PDF
50. Structure-activity relationship of 5-hydroxykynurenamine analogues in isolated dog cerebral arteries.
- Author
-
Fu LH and Toda N
- Subjects
- Aniline Compounds pharmacology, Animals, Dogs, Dose-Response Relationship, Drug, Female, Hydroxypropiophenone pharmacology, In Vitro Techniques, Kynuramine analogs & derivatives, Male, Muscle Contraction drug effects, Muscle, Smooth, Vascular drug effects, Serotonin, Serotonin Antagonists, Structure-Activity Relationship, Cerebral Arteries drug effects, Hydroxypropiophenone analogs & derivatives, Kynuramine pharmacology, Propiophenones pharmacology
- Abstract
In helically-cut strips of cerebral arteries isolated from dogs, analogues of 5-hydroxykynurenamine (5-HK), including 2-(3'-aminopropyl)-aniline (Cpd. I), 2'-amino-3-dimethylamino-3'-hydroxypropiophenone(CPD. II), 2'-amino-3-dimethylamino-5'-hydroxypropiophenone (Cpd. III) and 2',3-diamino-propiophenone (kynurenamine), caused a dose-related contraction which was antagonized by treatment with methysergide. The potency for inducing contractions was in the order of 5-hydroxytryptamine greater than 5-HK greater than Cpd. III greater than kynurenamine, Cpd. I and Cpd. II. Treatment with the 5-HK analogues antagonized the contractile response to 5-hydroxytryptamine in a dose-dependent manner, the antagonistic potency being in the order of 5-HK greater than Cpd. III greater than kynurenamine, Cpd. II greater than Cpd. I. Alterations in the hydroxy group on the benzene ring and/or radicals of long side chain of 5-HK attenuated the agonistic and antagonistic actions of 5-HK; however, the attenuation of these actions differed. Thus, the radicals appear to be involved in the agonistic and antagonistic actions to a different extent.
- Published
- 1979
- Full Text
- View/download PDF
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