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N Toda

Publications and source records attributed to N Toda.

At least 73 records · Page 4Linked to original sources
PubMed1997

Flunarizine, an anti-migraine agent, impairs nitroxidergic nerve function in cerebral arteries.

Flunarizine is an anti-migraine agent that blocks the Ca2+ entry across cell membrane. In order to obtain a clue of mechanisms underlying the migraine headache, modifications by flunarizine of the response to nitric oxide (NO), a cerebral vasodilator and algogenic agent, derived from perivascular nerves were evaluated. Relaxations due to nerve stimulation by electrical pulses (5 Hz) and nicotine (10(-4) M) in canine cerebral arterial strips were attenuated by treatment with flunarizine dose-dependently, whereas the responses to exogenous NO (10(-7)-10(-6) M) and nitroprusside (10(-8)-10(-6) M) were unaffected. The inhibition by the Ca2+ entry blocker of the response to electrical nerve stimulation and nicotine was obtained in a concentration (10(-6) M) that did not significantly relax the arterial strips. NO derived from perivascular nerve may be one of the factors involved in the genesis of migraine attack, which is expected to be relieved by a reduction of neural NO synthase activity associated with a decreased Ca2+ influx by flunarizine during nerve activation.

Animals↗
PubMed1997

Analysis of the vasodilator nerve function by nicotine in isolated dog skin artery.

Mechanisms underlying the relaxation induced by nicotine were analyzed in cutaneous arterial strips isolated from dogs and with the endothelium removed. In the strips treated with prazosin and precontracted with prostaglandin F2 alpha, nicotine produced relaxations which were not influenced by atropine but abolished by hexamethonium. Relaxations induced by nicotine were partially inhibited by NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor; the remaining relaxations were abolished by desensitization to calcitonin gene-related peptide (CGRP) or treatment with CGRP-(8-37), a CGRP receptor antagonist, or with capsaicin. Desensitization to vasoactive intestinal polypeptide (VIP) or a VIP receptor antagonist did not influence the nicotine-induced relaxation. In the strips densensitized to CGRP, the nicotine-induced relaxation was abolished by L-NA; the inhibitory effect was reversed by L-arginine. Perivascular nerves containing NADPH diaphorase and CGRP immunoreactivity were histochemically identified in the cutaneous artery. CGRP immunoreactivity was abolished by treatment with capsaicin. It is concluded that nicotine produces relaxation in dog cutaneous arterial strips, possibly mediated by NO and CGRP liberated from vasodilator nerves.

Animals↗
PubMed1997

Colocalization of acetylcholinesterase and vasoactive intestinal peptide (VIP) in nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) positive neurons in the intralingual ganglia and perivascular nerve fibers around lingual arteries in the porcine, monkey and canine tongue.

Distribution of nitric oxide synthase in the intrinsic ganglia in the porcine, monkey and canine tongue was histologically investigated using the reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) method, acetylcholinesterase histochemistry and vasoactive intestinal peptide (VIP) immunohistochemistry. The majority of intralingual ganglionic cells showed intense NADPH-d reactivity with positive acetylcholinesterase reaction or positive VIP immunohistochemistry. The NADPH-d positive, acetylcholinesterase-rich and the NADPH-d positive, VIP immunoreactive nerve fibers are particularly conspicuous around intralingual blood vessels. These fibers around the arteries in the tongue may be partly derived from the intralingual ganglion cells, because some bundles associated with these nerve cells were easily traced on the wall of blood vessels. The present study suggests the view that the three markers coexist in the axons and nerve terminals of these intralingual neurons.

Acetylcholinesterase↗
PubMed1997

Inhibition of nitroxidergic nerve function by neurogenic acetylcholine in monkey cerebral arteries.

1. Modification by endogenous or exogenous acetylcholine and vasoactive intestinal polypeptide (VIP) of vasodilatation mediated by nitric oxide (NO) released from nitroxidergic nerves was studied in isolated monkey cerebral arteries. In arterial strips denuded of endothelium, transmural electrical stimulation (2-20 Hz) produced relaxations that were abolished by tetrodotoxin. 2. The relaxation response was attenuated by acetylcholine, and the attenuation was reversed by atropine. Attenuation was also observed with AF-DX 116, an antagonist of the muscarinic acetylcholine receptor subtype, M2. NO-induced relaxation was not affected by acetylcholine. Neurogenic relaxation was also inhibited by physostigmine and potentiated by atropine. 3. VIP in concentrations that elicited slight relaxation did not alter the response to nerve stimulation. In the strips showing tachyphylaxis to VIP, the neurogenic response was not inhibited. 4. Histochemical studies of whole-mount preparations revealed nerve fibres with NO synthase and VIP immunoreactivity, and also acetylcholinesterase, suggesting the presence of perivascular nitroxidergic, VIPergic and cholinergic innervation. 5. It is concluded that the actions of nitroxidergic nerve fibres on the monkey cerebral artery are inhibited by nerve-released acetylcholine acting on prejunctional muscarinic receptors, possibly of the M2 subtype. Despite the presence of VIP immunoreactive nerve fibres and the ability of exogenous VIP to relax the artery, there is no evidence supporting either a prejunctional modulation of nitroxidergic nerve function by VIP or a role for VIP as a vasodilatory neurotransmitter.

Acetylcholine↗
PubMed1997

Hypoxia-induced inhibition of the response to nitroxidergic nerve stimulation in canine cerebral arteries.

In isolated canine middle cerebral arteries contracted with prostaglandin F2 alpha, transmural electrical stimulation (TES), nicotine, and substance P produced relaxations. Transmural electrical stimulation- and nicotine-induced endothelium-independent responses are mediated by nitric oxide (NO) liberated from perivascular nerve, whereas substance P-induced relaxations are mediated by endothelium-derived NO. These responses were attenuated by replacement of 95% O2 and 5% CO2 gas (about 550 mm Hg of partial O2 pressure) with 95% N2 and 5% CO2 gas (about 40 mm Hg); inhibition of the response to TES was stabilized 30 minutes later. Reoxygenation partially reversed the response. Relaxations caused by exogenous NO were not influenced by hypoxia. Inhibition by hypoxia of the response to TES was not affected by superoxide dismutase. However, the inhibitory effect was prevented by amiloride and dimethyl-amiloride, Na(+)-H+ exchange inhibitors, or acidosis caused by the addition of HCl. The inhibition by hypoxia was reversed by amiloride. It is concluded that depression by hypoxia of the response mediated by endogenous NO is associated with impaired membrane function caused by restoration of normal intracellular pH by Na(+)-H+ exchanger.

Acidosis↗
PubMed1997

Nitric oxide-mediated neurogenic vasodilatation in isolated monkey lingual arteries.

In isolated monkey lingual arteries denuded of the endothelium and contracted with prostaglandin F2alpha, transmural electrical stimulation produced a contraction that was reduced by prazosin and reversed to a relaxation by additional treatment with alpha,beta-methylene ATP. The relaxation thus induced was abolished by tetrodotoxin and N(G)-nitro-L-arginine (L-NNA), a nitric oxide (NO) synthase inhibitor, and L- but not D-arginine restored the response in the L-NNA-treated arteries. Under treatment with prazosin and alpha,beta-methylene ATP, the arterial strips responded to nicotine with a relaxation that was not influenced by atropine and timolol but was abolished by hexamethonium, oxyhemoglobin, and methylene blue. The nicotine-induced relaxation was abolished by L-NNA but not by N(G)-nitro-D-arginine and was reversed by L-arginine. Relaxations to exogenously applied NO (acidified NaNO2 solution) were not influenced by L-NNA but were abolished by oxyhemoglobin and methylene blue. The response was not affected in the strips made unresponsive to vasoactive intestinal polypeptide and calcitonin gene-related peptide by desensitization. Histochemical study demonstrated the presence of perivascular neurons containing neuronal NO synthase. It is concluded that monkey lingual arteries are innervated by vasoconstrictor nerves liberating norepinephrine and possibly ATP and also by nonadrenergic noncholinergic vasodilator nerves liberating NO as a neurotransmitter to activate soluble guanylate cyclase. Vasoactive intestinal polypeptide and calcitonin gene-related peptide do not appear to be involved in the neurogenic vasodilatation.

Adenosine Triphosphate↗
PubMed1997

Pelvic nerve stimulation-induced pressor responses in corpus cavernosum of anesthetized dogs.

To analyze the mechanism of penile erection and pathogenesis of impotence, pressures in the corpus cavernosum in anesthetized dogs were measured. Pelvic nerve stimulation produced pressor responses in a frequency-dependent manner. Intravenous injections of NG-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, dose dependently attenuated the response, and the inhibition was reversed by intravenous injection of L-arginine but not of D-arginine. The response was also inhibited by NG-nitro-L-arginine injected into the corpus cavernosum, the potency being approximately 10 times of that applied intravenously. The intracavernous injection of L-arginine restored the response. NG, NG-dimethylarginine, an endogenous NO synthase inhibitor, dose dependently attenuated the stimulation-induced response, which was restored by an intracavernous injection of L-arginine. An intravenous injection of hexamethonium abolished the pressor response to nerve stimulation, whereas phentolamine and atropine did not significantly alter the response. These findings suggest that an increase in intracavernous pressure caused by pelvic nerve stimulation in anesthetized dogs is mediated by NO liberated from postganglionic neurons that originate in the ganglion located in the vicinity of corpus cavernosum.

Animals↗
PubMed1997

beta1-Adrenoceptor-mediated relaxation by norepinephrine in dog hepatic arteries.

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.

Adrenergic alpha-Antagonists↗
PubMed1997

Inhibition by adrenomedullin of the adrenergic neurogenic response in canine mesenteric arteries.

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.

Adrenomedullin↗
PubMed1997

Prejunctional regulation by endogenous and exogenous acetylcholine of adrenergic nerve function in isolated canine mesenteric arteries.

Transmural electrical stimulation (5-30 Hz) produced a frequency-dependent increase in the perfusion pressure of isolated, perfused dog mesenteric artery segments without the endothelium, which was abolished by prazosin or tetrodotoxin. Physostigmine inhibited the pressor response to transmural electrical stimulation, whereas atropine potentiated the response. Treatment with acetylcholine (10(-6) and 10(-5) M) dose-dependently inhibited the response to electrical nerve stimulation. The effect was reversed by the addition of atropine and AF-DX 116 at a concentration (10(-7) M) that selectively blocked the M2 receptor subtype, but not by pirenzepine or 4-DAMP. Acetylcholine did not alter the pressure raised by norepinephrine in perfused arterial segments nor the contraction caused by exogenous norepinephrine in the artery strips. 3H-overflow evoked by transmural electrical stimulation from tissues prelabeled with [3H] norepinephrine was decreased by acetylcholine (10(-6) M) in the superfused dog mesenteric arterial strips. It is concluded that acetylcholine inhibits adrenergic neurogenic contractions by interfering with the release of norepinephrine, which possibly results from activation of the prejunctional M2 receptor subtype.

Acetylcholine↗
PubMed1997

Mechanism of adrenomedullin-induced relaxation in isolated canine retinal arteries.

PURPOSE: To analyze the mechanism of action of adrenomedullin (AM), a peptide recently isolated from human pheochromocytoma, in isolated canine central retinal arteries and to compare the action of calcitonin gene-related peptide (CCRP). METHODS: Changes in isometric tension were recorded in helical strips of the arteries with and without the endothelium. RESULTS: Both AM and CGRP produced relaxation: EC50s were 2.62 and 0.71 x 10(-9) mol/l, respectively, and maximal relaxations were 85.1% and 84.3%, respectively. The AM-induced relaxation was endothelium-independent and unaffected by indomethacin, Ng-nitro-L-arginine, methylene blue, and glibencaalmide. Treatment with [8-37] CGRP markedly inhibited the relaxations caused by AM and CGRP. Treatment with a high concentration of sodium nitroprusside abolished the relaxation caused by nitroglycerin and atrial natriuretic peptide and reduced the relaxation caused by AM and CGRP. A high concentration of beraprost, a stable analog of prostaglandin I2, suppressed the response to AM and CGRP but not to nitroglycerin. CONCLUSIONS: Endothelium-independent relaxations to AM of canine retinal arteries may be mediated primarily by intracellular cyclic adenosine monophosphate by stimulation of CGRP1 receptors and partially by cyclic guanosine monophosphate; cyclic guanosine monophosphate is unlikely ot be produced by methylene blue-sensitive soluble guanylate cyclase. Prostanoids, nitric oxide, and adenosine triphosphate-dependent K+ channel opening do not appear to be involved in the AM-induced relaxation.

Adrenomedullin↗
PubMed1997

Modulation by neurogenic acetylcholine of nitroxidergic nerve function in porcine ciliary arteries.

PURPOSE: To determine whether nitroxidergic, cholinergic, and vasoactive intestinal polypeptide (VIP)-mediated nerves participate in the regulation of porcine ciliary arterial tone and to analyze the mechanisms underlying the neuronal interaction. METHODS: Changes in isometric tension were recorded in helical strips of the arteries, which were stimulated by transmurally applied electrical pulses or nicotine. The presence of perivascular nerve fibers containing reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase, acetylcholinesterase, and VIP immunoreactivity were determined histologically. RESULTS: Transmural electrical stimulation (2, 5, and 20 Hz) and nicotine produced a relaxation of the arterial strips denuded of the endothelium and contracted with prostaglandin F2alpha. The response was not influenced by timolol but was abolished by oxyhemoglobin and methylene blue. N(G)-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, abolished the neurogenic relaxation, and L-arginine restored the response. Physostigmine inhibited, but atropine potentiated, the neurogenic response. The relaxation was attenuated by acetylcholine but was not influenced by VIP. There were nerve fibers and bundles containing NADPH diaphorase, acetylcholinesterase, and VIP immunoreactivity in the adventitia of ciliary arteries. CONCLUSIONS: Porcine ciliary arteries are innervated by NO synthase-containing nerves that liberate NO, possibly as a neurotransmitter on excitation to produce muscular relaxation. Nitroxidergic nerve function is inhibited by acetylcholine released from cholinergic nerve, possibly because of impaired production or release of NO. VIP does not seem to function as a neurotransmitter or a modulator.

Acetylcholine↗
PubMed1996

A transforming growth factor beta type II receptor gene mutation common in sporadic cecum cancer with microsatellite instability.

Mismatch repair genes are the responsible genes for hereditary non-polyposis colon cancer, and mutation of these genes causes replication error (RER). In several RER-positive colon cancer cell lines, mutations of repetitive sequences of transforming growth factor beta (TGF-beta) type II receptor (RII) gene have been reported. Since TGF-beta inhibits cell proliferation, loss of response to TGF-beta is an important tumor progression step. In this study, the relationship between RER status and mutation of the RII gene was analyzed in 112 cases of various types of sporadic gastrointestinal and hepatobiliary cancer (41 with gastric, 49 with colorectal, 5 with gallbladder, and 17 with hepatic cancers). RER was found in 17 cases (4 with gastric, 12 with colorectal, and 1 with gallbladder cancer), and 10 of those (3 with gastric and 7 with colorectal cancer) showed mutations of the RII gene. Of interest was that in all seven cases with colorectal cancer, tumors were located at the cecum. These data indicate that mutation of the RII gene, presumably caused by abnormality of repair gene, play an important role in carcinogenesis of sporadic gastrointestinal cancer, especially at the cecum.

Aged↗
PubMed1996

Pre- and postjunctional modulation by endothelin-1 of the adrenergic neurogenic response in canine mesenteric arteries.

Transmural electrical stimulation (5-30 Hz) produced a frequency-dependent increase in the perfusion pressure of isolated, perfused dog mesenteric artery segments, which was suppressed by prazosin and abolished by tetrodotoxin. Treatment with endothelin-1 in low concentrations (10(-10) and 3 x 10(-10) M) inhibited the response to electrical nerve stimulation. The effect was not affected by NG-nitro-L-arginine, indomethacin and removal of the endothelium. The endothelin-1-induced inhibition was antagonized by 10(-7) M BQ123[cyclo(D-Trp-D-Asp-L-Pro-D-Val-L-Leu-)sodium], an endothelin ETA receptor antagonist, but not by 10(-5) M BQ788 [N-cis-2,6-dimethyl-piperidinocarbonyl-L- gamma-methylleucyl-D-1-methoxycarbonyltryptophanyl-D-norleuc ine], an antagonist of endothelin ETB1 and ETB2 receptors. IRL1620 [Suc-[Glu9, Ala11,15]endothelin-1-(8-21)], a selective endothelin ETB1 receptor agonist, did not alter the response to electrical stimulation. However, raising the concentration of endothelin-1 to 10(-9) M or higher potentiated the response. Similar results were also obtained in mesenteric artery strips in response to electrical stimulation. Endothelin-1 at low concentrations did not alter the contraction caused by exogenous norepinephrine in the artery strips, whereas the peptide at high concentrations potentiated the response. 3H-overflow evoked by transmural electrical stimulation from tissues prelabeled with [3H]norepinephrine was decreased by endothelin-1 (3 x 10(-10) M) in the superfused dog mesenteric arteries. It is concluded that endothelin-1 at low concentrations activates prejunctional endothelin ETA receptors and inhibits adrenergic nerve-mediated contractions by an inhibition of amine release, whereas the peptide at high concentrations potentiates the neurally induced contractions by a postjunctional enhancement, via endothelin ETA receptors, of the action of norepinephrine. Low concentrations of endothelin-1 appear to act as a vasodilator in adrenergically innervated mesenteric artery

Animals↗
PubMed1996

NADPH diaphorase-positive neurons in the intracardiac plexus of human, monkey and canine right atria.

Distribution of nitric oxide synthase in intracardiac ganglion cells located in human, monkey and canine right atria was histologically investigated using the reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase method and acetylcholinesterase histochemistry. In the intracardiac ganglion, many large neurons exhibited both positive reactions, whereas some of the NADPH diaphorase-positive small neuronal cells were shown with negative acetylcholinesterase reaction.

Acetylcholinesterase↗
PubMed1996

Neurogenic nitric oxide (NO) in the regulation of cerebroarterial tone.

Sympathetic vasoconstrictor nerves are commonly recognized to mainly control the vascular smooth muscle tone, thus alters regional vascular resistance and blood flow. In contrast to peripheral organs and tissues, regulation by sympathetic nerves of blood flow in the brain is not so evident, and conversely vasodilator innervation is expected to play an important role. The mechanism underlying the neurogenic vasodilation in the cerebral artery has not been determined until recently. This problem was solved by the discovery of nitric oxide (NO) synthase inhibitors. Cerebral arterial dilatation caused by nerve stimulation is abolished by NO synthase inhibition and is restored by L-arginine, a substrate of NO synthase; vasodilator nerve stimulation increases the production of cyclic GMP in the tissue and liberates NOx (nitroxy compounds) from the arterial strip into superfusate. In addition, the presence of neurons containing NO synthase is histochemically demonstrated in the arterial wall. Neurogenic cerebral arterial dilation is thus hypothesized to be mediated by NO liberated as a neurotransmitter from the nerve. Nitroxidergic vasodilator innervation from the pterygopalatine ganglion would be important in the regulation of brain circulation.

Animals↗
PubMed1996

Endoscopic papillary balloon dilation in cirrhotic patients: removal of common bile duct stones without sphincterotomy.

BACKGROUND AND STUDY AIMS: Endoscopic papillary balloon dilation (EPBD) is a less invasive alternative to endoscopic sphincterotomy (EST). This study reviews a series of cirrhotic patients with bile duct stones who were treated with EPBD. PATIENTS AND METHODS: EPBD was used to remove common bile duct stones in nine cirrhotic patients (one in Child-Pugh grade A, four in grade B, and four in grade C). After the papilla was dilated with balloon-tipped catheter, the stones were removed with a retrieval basket catheter or a retrieval balloon, or both. Mechanical lithotripsy was required in two patients with stones of more than 1 cm in diameter. RESULTS: Clearance of the common bile duct was achieved in all patients without any serious complications such as hemorrhage or perforation. CONCLUSIONS: These results suggest that EPBD is a safe and effective technique for the treatment of common bile duct stones in patients with liver cirrhosis.

Aged↗