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N Toda

Publications and source records attributed to N Toda.

At least 109 records · Page 6Linked to original sources
PubMed1995

Functional role and histological demonstration of nitric-oxide-mediated inhibitory nerves in dog sphincter of Oddi.

Nitric oxide (NO) plays an important physiological role in regulating gastrointestinal motility. Involvement of endogenous NO was evaluated in the response to non-adrenergic, non-cholinergic (NANC) nerve stimulation of the dog sphincter muscle of Oddi. Transmural electrical stimulation (TES), nicotine (10(-5) M) and K+ (10 mM) produced only a relaxation in the sphincter muscle strips contracted with substance P, which was not potentiated by atropine. The TES-induced relaxation was abolished by tetrodotoxin (3 x 10(-7) M) and oxyhaemoglobin (1.6 x 10(-5) M), but not affected by atropine (10(-7) M), propranolol (10(-7) M), phentolamine (10(-7) M), indomethacin (10(-6) M), cholecystokinin (CCK, 10(-8) M) and vasoactive intestinal polypeptide (VIP, 10(-8) M). The relaxation was also abolished by treatment with NG-nitro-L-arginine (L-NA, 10(-5) M), an NO synthase inhibitor. Nicotine produced a transient relaxation, which was abolished by tetrodotoxin, hexamethonium (10(-5) M) and L-NA, but not affected by atropine and NG-nitro-D-arginine (D-NA, 10(-5) M). The addition of K+ elicited a transient relaxation, which was abolished by tetrodotoxin and L-NA. The inhibitory effects of L-NA were antagonized by L-arginine (10(-3) M). The presence of neurons containing nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase was histochemically demonstrated in the sphincter of Oddi. These findings may indicate that TES, nicotine and K+ liberate NO from NANC inhibitory nerve which is involved in the relaxation of the dog sphincter of Oddi. The muscular tone does not seem to be regulated by cholinergic nerves under the experimental conditions used.

Analysis of Variance↗
PubMed1995

Roles of peptides and other substances in cotransmission from vascular autonomic and sensory neurons.

Blood vessels may be innervated by up to three major classes of neurons: sympathetic vasoconstrictor neurons; sympathetic or parasympathetic vasodilator neurons; and peripheral fibres of small diameter sensory neurons, which can mediate vasodilation. Most vascular neurons utilise multiple transmitters, including neuropeptides and small nonpeptides such as ATP or nitric oxide, often in addition to noradrenaline or acetylcholine. Subpopulations of each major class of vascular neurons innervating different vascular segments may contain different combinations of neurotransmitters. Furthermore, the same population of neurons can release different cotransmitters in response to different patterns of stimulation. In general, peptides mediate slower and more long lasting changes in vascular resistance than do nonpeptides. Thus, autonomic and sensory neurons are well adapted to produce qualitatively different vascular effects in response to different types of afferent input. The major challenge for the future is to develop new antagonists for many of the substances colocalised in vascular neurons, particularly neuropeptides. These agents will allow us to precisely determine the relative roles of multiple cotransmitters, and are likely to provide therapeutic agents that can be targeted to specific regions of the vasculature.

Animals↗
PubMed1995

Characteristics of DQ2511-induced relaxation in isolated dog, monkey and human arteries.

DQ2511, a possible antiulcer agent, relaxed dog, monkey and human arterial strips from various organs; the effect was most evident in the gastroepiploic artery. The relaxation was not influenced by timolol, atropine, dopamine receptor antagonists, and K+-channel blockers, but partially attenuated by oxyhemoglobin endothelium denudation. Treatment with DQ2511 increased the relaxant response to sodium nitroprusside and a prostaglandin I2 analog in dog gastroepiploic arteries and potentiated the stimulating effect of these agonists on the contents of cyclic GMP and cyclic AMP, respectively. It is concluded that DQ2511 relaxes gastroepiploic arteries predominantly over the other arteries; the relaxation appears to be derived partially from phosphodiesterase inhibition.

Animals↗
PubMed1995

Nitroxidergic innervation in dog and monkey renal arteries.

We analyzed mechanisms underlying neurogenic vasodilatation in dog and Japanese monkey renal arteries. Isometric mechanical responses of the arterial strip to nerve stimulation by nicotine were recorded. Nicotine-induced contractions were abolished by hexamethonium and potentiated by NG-nitro-L-arginine, a nitric oxide synthase inhibitor. The potentiating effect was reversed by L-arginine. NG-Nitro-L-arginine did not potentiate the contraction caused by norepinephrine. The nicotine-induced contraction was reversed to a relaxation by prazosin. The relaxation was not influenced by indomethacin, timolol, or atropine but was abolished by NG-nitro-L-arginine, methylene blue (a guanylate cyclase inhibitor), oxyhemoglobin (a nitric oxide scavenger), and hexamethonium. In the strips treated with NG-nitro-L-arginine, the nicotine-induced relaxation was restored by L-arginine. Histochemical study demonstrated perivascular nerves containing NADPH diaphorase and nitric oxide synthase immunoreactivity in dog and monkey arteries. We conclude that renal arteries are innervated by nitric oxide-mediated vasodilator and adrenergic vasoconstrictor nerves, and depression of the vasodilator nerve function by nitric oxide synthase inhibition potentiates the contraction caused by adrenergic nerve excitation.

Animals↗
PubMed1995

[Effect of the novel calcium antagonist AE0047 on responses of isolated dog blood vessels to vasoconstricting agents and to nerve stimulation].

The effect of AE0047 on contractile responses to high K+ and agonists and to perivascular nerve stimulation was investigated using isolated dog cerebral, coronary and mesenteric arteries and mesenteric veins. AE0047 inhibited concentration-dependent contractions induced by KCl, norepinephrine, prostaglandin (PG) F2 alpha and serotonin. The inhibition of contractions caused by PGF2 alpha and serotonin was greater in cerebral arteries than in mesenteric arteries. The inhibitory effect of AE0047 on norepinephrine-induced mesenteric arterial contraction persisted for 24 hr or longer even though the strips were repeatedly washed. Greater inhibition was obtained in the arteries contracted with K+ than in those contracted with agonists. AE0047 reduced Ca(2+)-induced contraction in K(+)-depolarized mesenteric artery strips to a greater extent than those in PGF2 alpha-stimulated strips. The relaxation induced by transmural electrical stimulation in coronary arteries treated with phenotolamine was reduced by AE0047, whereas the norepinephrine-induced relaxation was unaffected. In cerebral arteries treated with superoxide dismutase, AE0047 reduced nicotine-induced relaxation but not NO-induced relaxation. These findings suggest that AE0047 selectively inhibits vasocontractions via voltage-dependent Ca channels and preferentially inhibits cerebroarterial contraction, these actions being long-lasting. AE0047 appears to reduce the release of neurotransmitter from adrenergic and nitroxidergic nerve terminals in blood vessels.

Animals↗
PubMed1995

Nitric oxide-mediated neurogenic relaxation in monkey mesenteric veins.

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.

Animals↗
PubMed1995

Nitroxidergic nerves and hypertension.

We studied vasodilator innervation in canine cerebral arteries and analyzed mechanisms of neurally induced vasodilatation. Available pharmacological, biochemical and histological evidence supports the hypothesis that nitric oxide (NO) synthesized in nerve terminals acts as a neurotransmitter that activates soluble guanylate cyclase in vascular smooth muscle and increases the production of cyclic GMP, resulting in relaxation. Peripheral arteries, such as the mesenteric, temporal, saphenous, uterine, and retinal, arteries, respond to nerve stimulation with contractions that are reversed to relaxations by alpha-adrenoceptor blockade. The relaxation is also mediated by NO derived from perivascular nerves. Thus, reciprocal regulation by NO-mediated (nitroxidergic) and adrenergic nerves is speculated. Potentiation by NO synthase inhibitors of the arterial contraction associated with adrenergic nerve stimulation in vitro is ascribed to depressed vasodilator nerve function. Systemic blood pressure in anesthetized dogs is increased by intravenous injections of NO synthase inhibitors. Our evidence strongly suggests that the pressor response is associated with suppressed synthesis and release of NO derived mainly from vasodilator nerves. It is concluded that nitroxidergic vasodilator nerves play important roles in the regulation of vascular tone in vitro and in vivo and in the control of systemic blood pressure. Presented here are new concepts for the mechanism of hypertension and the role played by NO-mediated nerve function.

Animals↗
PubMed1995

Comparison of the effect of dopamine in primate arteries and veins.

Mechanical responses to dopamine of isolated human and monkey veins were isometrically measured and compared to those of the arteries. Human gastroepiploic and monkey mesenteric veins responded to dopamine with contractions, whereas the arteries in the same region responded with relaxations. Treatment with phentolamine converted the venous contraction to a relaxation, which was not influenced by propranolol but was abolished by droperidol. The relaxation was endothelium-independent and converted to a contraction by SCH23390 but unaltered by domperidone. Dopamine increased the cyclic AMP content in the human veins. Monkey vena cava and portal vein did not respond to dopamine with relaxation even under alpha-adrenoceptor blockade. It is concluded that primate veins and arteries from the gastric and mesenteric regions respond quite differently to dopamine; the alpha-adrenoceptor-mediated contraction predominates over the relaxation mediated via D1-receptor in the veins, and vice versa in the arteries. In monkey large veins, dopamine receptor does not appear to play a functional role. The veno-constrictor action of dopamine, together with actions on myocardium and resistance vessels, would contribute to increasing of the cardiac output.

Animals↗
PubMed1995

Distribution of NADPH diaphorase-reactive nerves in the human female genital organ.

OBJECTIVE: This study was designed to histochemically clarify the presence of nerves containing NADPH diaphorase, representing the catalytic activity of nitric oxide synthase, in the human female genital organ. STUDY DESIGN: Female genital organs were isolated for NADPH diaphorase staining by extensive or simple hysterectomy from ten patients. RESULTS: Paracervical ganglia contained many nerve cells intensely stained. The nerve from the ganglia contained many axons intensely stained, which selectively innervated blood vessels distributing to the whole genital organ. NADPH diaphorase-reactive nerve fibers around the vascular wall distributed in the adventitia, closely contacting to the medial layer. The distribution of the axons was much denser in the arterial wall than in the venous wall. CONCLUSION: The NADPH diaphorase-reactive nerve fibers, possibly originated from paracervical ganglia, appear to play an important role in the regulation of uterine vascular tone by liberating nitric oxide, and such a neurogenic control may be predominant in the artery over the vein.

Amino Acid Oxidoreductases↗
PubMed1995

Mechanisms underlying endothelium-independent relaxation by acetylcholine in canine retinal and cerebral arteries.

Canine retinal central arterial strips responded to acetylcholine with a relaxation that was endothelium-independent. Indomethacin and atropine abolished the relaxation at low doses (10(-7) to 10(-6) M) and moderately attenuated the response to high concentrations (10(-5) and 10(-4) M). The residual relaxation at 10(-5) and 10(-4) M in indomethacin-treated strips were abolished by NG-nitro-L-arginine, hexamethonium, oxyhemoglobin and methylene blue, and the NG-nitro-L-arginine-induced inhibition was reversed by L-arginine. Cerebral arterial strips with endothelium responded to acetylcholine with a transient relaxation followed by a contraction, whereas only a relaxation was induced when endothelium was denuded. The relaxations at low and high doses were modified by atropine, indomethacin, hexamethonium and NG-nitro-L-arginine quite similarly to those seen in retinal arteries. Histochemical study demonstrated the presence of perivascular nerves containing NADPH diaphorase in whole mount preparations of the retinal artery. It is concluded that acetylcholine-induced retinal arterial relaxations, independent of endothelium, are mediated possibly by prostaglandin I2 in activation of muscarinic receptors and by nitric oxide derived from perivascular nerves in response to nicotinic receptor stimulation. On the other hand, vasoconstrictor prostanoids appear to be liberated from the endothelium by muscarinic receptor stimulation in cerebral arteries, and mechanisms underlying the relaxation are similar to those seen in retinal arteries.

Acetylcholine↗
PubMed1995

Functional role of nerve-derived nitric oxide in isolated dog ophthalmic arteries.

PURPOSE: To determine if nitric oxide (NO) is involved in the relaxant response to nerve stimulation by nicotine and electrical pulses in dog external ophthalmic arteries (EOA) and internal ophthalmic arteries (IOA). METHODS: Changes in isometric tension were recorded in helical strips of the arteries, and the presence of perivascular nerve containing NADPH diaphorase was histochemically demonstrated. RESULTS: Nicotine (10(-4) M, EOA and IOA) and transmural electrical stimulation (5 Hz, EOA) produced a slight or no contraction followed by a moderate relaxation in the strips contracted with prostaglandin F2 alpha. The contraction was abolished by alpha-adrenoceptor antagonists. The relaxation was abolished and the contraction was potentiated by NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor; the relaxation was reversed by L-arginine. Contractile response in L-NA-treated EOA was greater than in the IOA, and the relaxation was less in nontreated EOA. NO-induced relaxation and norepinephrine-induced contraction were not influenced by L-NA. There were plenty of nerve fibers visualized by NADPH diaphorase staining method in the adventitia of EOA and IOA, indicating the presence of NO synthase-containing nerves. CONCLUSIONS: The neurogenic relaxation appears to be mediated by NO released from the vasodilator nerve in EOA and IOA. There is a reciprocal innervation in vasodilator nitroxidergic and vasoconstrictor noradrenergic nerves; functionally, the latter is more predominant in EOA than in IOA.

Animals↗
PubMed1995

Basilar arterial construction caused by intracisternal NG-nitro-L-arginine in anesthetized monkeys.

OBJECTIVES: The present study was designed to determine whether tonic nitric oxide (NO)-mediated vasodilator innervation participates in basilar arterial dilatation in the anesthetized Japanese monkey. METHODS: The basilar arterial diameter was angiographically measured, and NG-nitro-L-arginine (L-NNA), a nitric oxide synthase inhibitor, was intracisternally applied. RESULTS: The injection of L-NNA produced a sustained constriction of the basilar artery, the effect being reversed by the cisternal injection of L-arginine. The vasoconstriction tended to be accelerated by treatment with phentolamine. Under alpha-adrenoceptor blockade, hexamethonium significantly attenuated the vasoconstrictor response to L-NNA. Intracisternal injections of this inhibitor did not alter the systemic blood pressure and heart rate. CONCLUSIONS: These findings suggest that construction by the NO synthase inhibitor of the monkey basilar artery is associated with suppression of synthesis of NO in vasodilator nerves receiving tonic impulses from the central nervous system. The basilar arterial tone appears to be regulated by nitroxidergic and adrenergic nerves and by NO derived from the endothelium in anesthetized monkeys.

Angiography, Digital Subtraction↗
PubMed1994

Distribution of immunoreactive malondialdehyde-modified low-density lipoprotein in human serum.

We developed a sensitive enzyme-linked immunosorbent assay (ELISA) for detection of malondialdehyde-modified low-density lipoprotein (MDA-LDL) in human serum. A monoclonal antibody against MDA-LDL (ML25) used in our method recognized not only MDA-LDL but also other MDA-modified proteins. However, MDA-LDL was able to be detected specifically by using a combination of ML25 and an antibody specific for apolipoprotein B (apo B) (AB16), which was conjugated with beta-galactosidase. Using this method, measurable amounts of MDA-LDL were detected in the sera of 40 healthy individuals. MDA-LDL was observed to be mainly distributed in the human LDL fraction separated by density gradient ultracentrifugation, while in each lipoprotein subfraction the largest amount of MDA-LDL per protein was found at a subfraction between LDL and HDL. The particle size of LDL in this fraction was smaller than that of LDL in the main LDL fraction, as assessed by electrophoresis. In addition, LDL oxidized by Cu2+ was also detectable with this method. We conclude that our method is sensitive and specific for MDA-LDL and might be useful for investigating MDA-LDL in the human circulation.

Antibodies, Monoclonal↗
PubMed1994

Sciatic nerve regeneration navigated by laminin-fibronectin double coated biodegradable collagen grafts in rats.

Biodegradable type I collagen tube grafts filled longitudinally with laminin and fibronectin double coated collagen fiber bundles (L-F grafts) were implanted to promote sciatic nerve regeneration in rats. Grafts filled with uncoated collagen fibers were used as control. A 1 cm defect on the right sciatic nerve was filled with a graft in the manner of bridging. Thirty days after implantation, several newly developed nerve fasciculi were found at the middle portion of the L-F grafts in contrast to no developed nerves in the controls. After 60 days, the middle and distal portions of both grafts included well-developed nerve tissues with prominent myelinated and unmyelinated nerve fibers surrounded by perineural cells, but the control distal portion showed fewer nerve fibers. All artificial collagen elements were completely degraded and absorbed at 30 days, and new nerve tissues surrounded by an epineurium successfully connected the proximal stump to the distal stump of the initially separated nerve. Descending and ascending action potentials were evoked in all grafts at 60 days. These results indicated that laminin and fibronectin may promote the growth of axons in biodegradable collagen grafts, which guided nerve regeneration well and allowed the formation of epineurium.

Animals↗
PubMed1994

Mechanism underlying nicotine-induced relaxation in dog saphenous arteries.

In isolated dog saphenous arterial strips denuded of the endothelium, the mechanism underlying relaxations induced by nicotine was analyzed. Nicotine-induced contractions were abolished by treatment with prazosin and alpha,beta-methylene ATP. In the strips thus treated and contracted with prostaglandin F2 alpha, nicotine produced a relaxation, which was abolished by hexamethonium. The relaxation was inhibited by cyclooxygenase inhibitors and markedly attenuated in the strips made tachyphylactic to calcitonin-gene related peptide (CGRP) but not to vasoactive intestinal polypeptide. The remaining relaxation in the strips treated with indomethacin and CGRP was abolished by NG-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, and the inhibition was reversed by L-arginine but not by D-arginine. Perivascular nerves containing NO synthase immunoreactivity have been demonstrated in an earlier report. CGRP-immunoreactive nerve fibers were observed in the adventitia. It appears that the nicotine-induced relaxation is associated with stimulation of vasodilator nerves liberating NO and CGRP, and adrenergic neurogenic vasoconstriction predominates over the neurogenic vasodilatation in dog saphenous arteries.

Animals↗
PubMed1994

Inhibition by calmodulin antagonists of the neurogenic relaxation in cerebral arteries.

The present study was aimed to determine the effect of calmodulin inhibitors on the relaxant response of isolated dog and monkey cerebral arteries to vasodilator nerve stimulation, which is hypothesized to be mediated by nitric oxide (NO) from nerve endings. The relaxations caused by nerve stimulation by electrical pulses in endothelium-denuded arteries were attenuated by treatment with calmidazolium and W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide hydrochloride) and were abolished by NG-nitro-L-arginine, an inhibitor of nitric oxide synthase, and tetrodotoxin. The calmodulin inhibitors also attenuated the relaxations caused by nicotine and substance P, which were endothelium-independent and -dependent, respectively, but did not influence the relaxant response to NO. It is concluded that calmodulin is required for activation of the NO synthase present in the vasodilator nerve as well as that in the endothelium.

Animals↗
PubMed1994

Nitric oxide (NO)-mediated, vasodilator nerve function and its susceptibility to calcium antagonists.

Our pharmacological and immunohistochemical studies have demonstrated that nitric oxide (NO) or a substance that liberates NO plays a crucial role in the neurogenic relaxation of isolated cerebral arteries of dog and monkey. Relaxation caused by nerve stimulation by nicotine or electrical pulses in dog cerebral arteries without the endothelium were attenuated by Cd2+, a non-selective Ca2+ channel antagonist. Increase in cyclic GMP by nicotine was also suppressed by Cd2+, but not by nicardipine. Treatment with capsaicin did not influence the relaxant responses of the endothelium-denuded cerebral arteries to nerve stimulation. These results suggest that neurotransmission in vasodilator nerves innervating dog cerebral arteries is mainly mediated by NO, synthesized by an NO synthase which is activated by Ca2+ influx through non-L-type Ca2+ channel, but not by vasodilator peptides.

Animals↗