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N Toda

Publications and source records attributed to N Toda.

At least 91 records · Page 5Linked to original sources
PubMed1996

Hypercapnia relaxes cerebral arteries and potentiates neurally-induced relaxation.

The present study was designed to determine whether relaxations induced by hypercapnia depend upon nitric oxide (NO) derived from the endothelium, and whether NO-mediated relaxant response to electrical and chemical stimulation of vasodilator nerves is modulated by hypercapnia. In canine and monkey cerebral arterial strips contracted with K+, raising the level of CO2 of the aerating gas in the bathing media from 5 to 10% produced a moderate relaxation, together with an increased Pco2 (from 29.8 to 59.3 mm Hg) and a decreased pH (from 7.43 to 7.15). Relaxation was not influenced by endothelium denudation and treatment with NG-nitro-L-arginine. Contractions elicited by the NO synthase inhibitor were attenuated by the removal of the endothelium. Relaxations, caused by transmural electrical stimulation and nicotine, of canine cerebral arterial strips contracted with prostaglandin F2 alpha, were potentiated only slightly by hypercapnia, but the potentiation of the response to exogenous NO (acidified NaNO2) was clearly greater. It is concluded that as far as the arteries used are concerned, hypercapnia does not seem to liberate NO from the endothelium but does potentiate the effect of NO. The reason for lesser potentiation, by hypercapnia, of the response to nitroxidergic nerve stimulation than to NO action may be associated with an impairment by intracellular acidosis of NO synthase activation.

Animals↗
PubMed1996

Keratinocyte growth factor is an endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture.

Mesenchymal-epithelial interactions are important in the gastric mucosal repair. However, specific factors responsible for such interactions have not been established. In the present study, keratinocyte growth factor (KGF) significantly stimulated proliferation of gastric epithelial cells dose dependently and synergistically with hepatocyte growth factor (HGF), epidermal growth factor (EGF) and insulin. Restitution of gastric epithelial monolayers was also assessed, using a round wound restitution model. Keratinocyte growth factor facilitated the restitution of gastric epithelial cells significantly but did not have any effects on gastric fibroblasts. Keratinocyte growth factor receptor mRNA was expressed by gastric epithelial cells, indicating that these effects were elicited by the specific receptor mediated pathway. Northern blot analysis revealed the expression of KGF mRNA in gastric fibroblasts but not in gastric epithelial cells, indicating the production of KGF. These results suggest that KGF might be involved in gastric mucosal repair, through mesenchymal-epithelial interaction.

Animals↗
PubMed1996

Canine retinal arterial and arteriolar dilatation induced by nipradilol, a possible glaucoma therapeutic.

The effects of nipradilol, an ocular hypotensive drug, on isolated canine retinal central arteries and on retinal arterioles in vivo were investigated. Nipradilol (10(-9) to 10(-5) mol/l) produced a dose-related relaxation of the arterial strips contracted with prostaglandin F2 alpha which was not influenced by timolol or indometacin. The median effective concentration of this drug was five times that of glycerol trinitrate (GTN). The nipradilol-induced relaxation in the endothelium-intact strips was not influenced by NG-nitro-L-arginine, a nitric oxide synthase inhibitor, but was abolished by oxyhemoglobin and methylene blue. Treatment with high concentrations of sodium nitroprusside abolished the response to nipradilol, as observed with that to GTN. Retinal arterial strips responded to isoproterenol with a slight relaxation which was depressed by nipradilol. In anesthetized dogs, intra-arterial injections of nipradilol dilated the retinal arterioles in the ocular fundus; the dilator potency was approximately one fifth that of GTN. It is concluded that nipradilol dilates canine retinal arteries in vitro and arterioles in vivo, possibly due to activation of soluble guanylate cyclase and increased production of cyclic guanosine monophosphate that are associated with nitric oxide liberated from the molecule itself in the tissue but not derived from the endothelium and perivascular nerve. Beta adrenoceptor blocking action was determined in the retinal artery.

Animals↗
PubMed1996

Neural mechanism of pressor action of nitric oxide synthase inhibitor in anesthetized monkeys.

Intravenous injection of NG-nitro-L-arginine (L-NA), a nitric oxide synthase inhibitor, elevated mean blood pressure by 29.0 +/- 4.9 mm Hg and decreased heart rate by 40.7 +/- 5.6 beats per minute in anesthetized Japanese monkeys (n = 6), whereas NG-nitro-D-arginine was without effect. After pretreatment with pentolinium, the magnitude of the pressure elevation by L-NA was significantly less than that after pretreatment with phentol-amine. The reduced blood pressure by either of the pretreatment drugs was compensated to control levels by a continuous infusion of angiotensin II before L-NA administration. Isolated monkey distal mesenteric arteries (150 to 200 microns OD) without endothelium responded to nerve stimulation by nicotine with a contraction, which was abolished by prazosin alone or in combination with alpha, beta-methylene ATP. In the strips thus treated and contracted with prostaglandin F2 alpha, nicotine caused a relaxation that L-NA abolished. L-NA but not NG-nitro-D-arginine reversed the inhibition. Histochemical staining of NADPH diaphorase, considered to be identical to nitric oxide synthase in neuronal tissues, demonstrated that positively stained nerve fibers were consistently present in the adventitia of monkey distal mesenteric arteries and arterioles. These results strongly suggest that nitroxidergic vasodilator nerves innervate peripheral small arteries and arterioles in the monkey and that these nerves participate in the regulation of systemic blood pressure. High blood pressure caused by nitric oxide synthase inhibitors is associated with an elimination of nitroxidergic nerve function together with an impairment of the basal release of nitric oxide from the endothelium.

Animals↗
PubMed1996

Comparison of neurogenic contraction and relaxation in canine corpus cavernosum and penile artery and vein.

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.

Adrenergic alpha-Antagonists↗
PubMed1996

Neurogenic nitric oxide mediates relaxation of canine corpus cavernosum.

PURPOSE: The aim of the present study is to analyze mechanisms underlying neurogenic relaxation of the corpus cavernosum which are believed to participate in penile erection. MATERIALS AND METHODS: Mechanical responses to nerve stimulation by electrical pulses and nicotine were measured in strips of canine corpus cavernosum precontracted with phenylephrine. Cyclic guanosine monophosphate (GMP) contents in the strips were also measured by radioimmunoassay. Immunohistochemistry for nitric oxide synthase (NOS) and vasoactive intestinal polypeptide (VIP) was performed. RESULTS: Transmural electrical stimulation and nicotine produced relaxations in the isolated canine corpus. The neurogenic relaxation was abolished by N omega-nitro-L-arginine, a NOS inhibitor, and the inhibition was reversed by L-arginine. Relaxations induced by nerve stimulation and exogenous nitric oxide (NO) were depressed by oxyhemoglobin and methylene blue. Vasoactive intestinal polypeptide (VIP)-induced relaxations were not influenced by these inhibitors. In the controls strips and those made unresponsive to VIP by its repeated application, the responses to nerve stimulation did not differ. The content of cyclic GMP in the tissue increased in response to nicotine, the effect being abolished by the NO synthase inhibitor. Immunohistochemical study demonstrated neurons containing NOS and VIP. CONCLUSIONS: It appears that the relaxation induced by nerve stimulation is mediated solely by NO liberated from the nerve that activates soluble guanylate cyclase and increases the production of cyclic GMP in smooth muscle, whereas VIP does not play a role in the regulation of muscle tone under the experimental conditions used.

Animals↗
PubMed1996

Monkey central retinal artery is innervated by nitroxidergic vasodilator nerves.

PURPOSE: To determine whether the monkey central retinal artery is innervated by vasodilator nerves and to analyze the mechanism underlying the neurogenic response. 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 nitric oxide (NO) synthase immunoreactivity was determined histologically. RESULTS: Transmural electrical stimulation (5 Hz) and nicotine produced a relaxation of the arterial strips denuded of the endothelium, treated with prazosin, and contracted with prostaglandin F2 alpha. The response was not influenced by timolol, atropine, and indomethacin, but it was abolished by methylene blue and oxyhemoglobin. NG-nitro-L-arginine, a NO synthase inhibitor, abolished the neurogenic relaxation, and L-arginine restored the response. Antagonists of calcitonin gene-related peptide and vasoactive intestinal polypeptide in sufficient concentrations did not influence the response to nerve stimulation by nicotine. There were abundant nerve fibers and bundles containing NO synthase immunoreactivity in the adventitia. CONCLUSIONS: Monkey central retinal arteries are innervated by NO synthase-containing nerves that liberate NO possibly as a neurotransmitter on excitation to produce muscular relaxation.

Animals↗
PubMed1995

Prejunctional modulation of nitroxidergic nerve function in canine cerebral arteries.

Modulation by acetylcholine, VIP, clonidine, omega-conotoxin and Mg2+ of the relaxant response to electrical and chemical stimulation of nitroxidergic nerves, in which nitric oxide (NO) acts as a neurotransmitter, was investigated in isolated canine cerebral arteries. Acetylcholine attenuated the response, the inhibition being reversed by atropine; however, physostigmine failed to reduce the response. VIP in submaximal doses did not alter the neurally induced relaxation. The same was true with clonidine, morphine and naloxane. Treatment with omega-conotoxin depressed the response to electrical nerve stimulation but did not influence the nicotine-induced relaxation. Mg2+ inhibited the relaxation caused by nerve stimulation and Ca2+ reversed the response. It is concluded that activation of prejunctional muscarinic receptors seems to inhibit the synthesis of release of NO from nerve terminals but endogenous acetylcholine from cholinergic nerve does not play a role in inhibiting the nitroxidergic nerve function. Prejunctional VIP, alpha 2, adrenergic and opioid receptors are not likely to participate in the regulation of nerve function. Ca2+ responsible for NO synthase activation would be produced into nerve terminals via N-type Ca2+ channels when electrically stimulated and via non-N-, non-L-type channels when stimulated by nicotine. Mg2+ and Ca2+ counteract in the neurally induced relaxation, although the underlying mechanism was not determined.

Acetylcholine↗
PubMed1995

Nitroxidergic nerve stimulation relaxes human uterine vein.

The predominant action of nitroglycerin, a nitric oxide (NO) donor, on veins over arterioles is well recognized. This study was carried out to determine whether endogenous NO derived from vasodilator nerve regulates the tone of human uterine venous strips. The isolated vein partially contracted with prostaglandin F2 alpha responded to nicotine with a contraction or a relaxation; the contraction was reversed to a relaxation by prazosin, and the relaxation was potentiated by the alpha 1-adrenoceptor antagonist. In prazosin-treated strips, nicotine-induced relaxations were not affected by timolol, atropine and indomethacin but were abolished by oxyhemoglobin and NG-nitro-L-arginine (L-NA), a NO synthase inhibitor. The D-enantiomer was without effect. The inhibition by L-NA was reversed by L-arginine. The NO-induced relaxation was not influenced by L-NA but was abolished by oxyhemoglobin. It may be concluded that the human uterine vein is innervated by vasodilator nerves from which NO is liberated as a vasodilator neurotransmitter. Norepinephrine from adrenergic nerves contracts venous smooth muscle possibly via stimulation of alpha 1-adrenoceptors.

Adult↗
PubMed1995

Fine localization of low and high calcium dependent ATPase activities in the rat sciatic nerve.

We tried to demonstrate the electron microscopic histochemical localization of membrane Ca(2+)-ATPase activity in glutaraldehyde-fixed rat sciatic nerves. Although conventional glutaraldehyde fixatives containing impurities interfered with the reactivity of Ca(2+)-ATPase, this activity was successfully preserved in the tissues fixed with pure glutaraldehyde as well as in those fixed with paraformaldehyde. In unmyelinated nerve fibers, an ATPase activity depending on 10 mM CaCl2 was detected on the whole external surface of Schwann cell plasma membranes. In myelinated fibers, this activity was localized on the surface of Schwann cell outer loops at the paranodal region of Ranvier nodes and on the axonal membrane at the nodal region. Another activity depending on 0.1 mM CaCl2 was demonstrated on the axolemma of unmyelinated fibers. These results indicated that there may be two types of Ca(2+)-ATPase activities showing high and low affinity to calcium ions localized in peripheral nerve systems in a different manner between myelinated and unmyelinated fibers.

Animals↗
PubMed1995

Comparison of responses of canine pulmonary artery and vein to angiotensin II, bradykinin and vasopressin.

Responses to angiotensin II, bradykinin and arginine vasopressin were compared in helical strips of canine pulmonary arteries and veins. Angiotensin II contracted the artery but relaxed the vein strip. The artery contraction was augmented by indomethacin and aspirin and was abolished by losartan. The vein relaxation was not affected by endothelium denudation but was abolished by the cyclooxygenase inhibitors, a prostaglandin I2 synthase inhibitor and losartan. The bradykinin-induced artery relaxation was inhibited by endothelium denudation, NG-nitro-L-arginine (L-NA) or indomethacin and abolished by their combined treatment. The vein relaxation produced by bradykinin was endothelium-independent and was abolished by indomethacin. Vasopressin produced a slight relaxation in the arteries, which was abolished by endothelium denudation and L-NA. The vein relaxation produced by vasopressin was abolished by endothelium denudation and combined treatment with L-NA and indomethacin. It may be concluded that (1) activation of angiotensin AT1 receptor subtype in smooth muscle produces contraction and also relaxation due to prostaglandin I2 release; the former predominates over the latter in the artery, whereas only the latter is operative in the vein, (2) the bradykinin-induced relaxation is due to nitric oxide (NO) from the endothelium and prostaglandin I2 from subendothelial tissues in the artery and solely to prostaglandin I2 in the veins, and (3) the vasopressin-induced relaxation is mediated by endothelial NO in the artery, and NO and prostaglandin I2 in the vein.

Angiotensin II↗
PubMed1995

Characteristic difference of hepatocellular carcinoma between hepatitis B- and C- viral infection in Japan.

Characteristics of 205 consecutive patients with hepatocellular carcinoma (HCC) admitted during 1990 to 1993 have been analyzed from the standpoint of hepatitis viral infection in Japan. Among 205 HCC patients, 71% of the patients showed positivity for hepatic C virus (HCV) antibody alone, 13% showed positivity both for HCV and HBV (HCV/HBV) antibody, 11% demonstrated HBsAg alone, and negativity of both HCV and HBV antibody in 4% only. Positivity to both HCV antibody and HBsAg was demonstrated in 1% only. Mean detection age of HCVAb-positive HCC as well as both HCV/HBV antibody-positive HCC was 62 +/- 7 years, in contrast to 52 +/- 13 years in HCC with HBsAg (P < .05). Male-to-female ratio among HCVAb-positive HCC was 3.3:1, in contrast to 5.5:1 among the HCV/HBVAb-positive HCC and 7:1 among HBsAg-positive HCC, but there was no significant difference in the gender distribution between these groups. More than 60% of HCVAb-positive HCC and HCV/HBVAb-positive HCC were classified into the stage of Child B and C, whereas 65% of HBsAg-positive HCC was at the stage of Child A. The severity of liver disease was confirmed by liver histology, indicating that more than 70% of the HCVAb-positive HCC and the HCV/HBVAb-positive HCC showed cirrhosis, in contrast to 50% among the HBsAg-positive HCC. Three-year survival rate of HCV Ab-positive HCC and HBV/HCVAb-positive HCC was 68% and 56%, respectively, in contrast to 47% in HBsAg-positive HCC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Histamine actions in dog retinal central arteries as compared to those in middle cerebral and temporal arteries.

PURPOSE: Mechanisms underlying the relaxant response to histamine were compared in isolated dog retinal arteries (branch of internal and external carotid arteries), middle cerebral arteries (branch of internal carotid artery) and superficial temporal arteries (branch of external carotid artery). METHODS: Changes in the isometric tension of helical strips of the arteries with and without the endothelium were recorded. RESULTS: Histamine produced concentration-related biphasic (phasic and sustained) relaxations in retinal arterial strips contracted partially with prostaglandin (PG)F2 alpha. Relaxations induced by histamine were not dependent on the endothelium. Treatment with cimetidine attenuated the sustained relaxation, whereas chlorpheniramine or indomethacin depressed the phasic relaxation. In addition, the phasic relaxant response to histamine was attenuated by tranylcypromine, a PGI2 synthesis inhibitor. In contrast, the amine-induced relaxant responses in dog middle cerebral arterial branch and temporal arteries were markedly suppressed by cimetidine alone. CONCLUSIONS: In dog retinal arteries, the phasic relaxation caused by histamine is mediated by PGI2 in association with activation of the H1 receptor subtype in subendothelial tissues, possibly smooth muscle, and the sustained relaxation is evoked by direct stimulation of the H2 receptor subtype in smooth muscle. The histamine-induced relaxation in temporal and distal middle cerebral arteries is associated solely with a stimulation of H2 receptors in smooth muscle.

Animals↗
PubMed1995

Neurogenic vasodilation in canine uterine and iliac arteries.

OBJECTIVE: To investigate neurogenic control of uterine and iliac arterial tone with reference to nerve-derived nitric oxide. DESIGN: Mechanisms underlying the response to perivascular nerve stimulation were studied under alpha-adrenoceptor blockade. METHODS: Mechanical responses to nerve stimulation by nicotine were isometrically recorded in isolated canine uterine and iliac arterial strips. Nitric oxide synthase was stained immunohistochemically. RESULTS: The arterial strips responded to nicotine mainly with a contraction, which was reversed to a relaxation by prazosin. The responses were abolished by hexamethonium. The relaxation was not influenced by timolol and atropine but was suppressed by NG-nitro-L-arginine, a nitric oxide synthase inhibitor; the inhibition was reversed by L-arginine. Internal iliac arterial strips also responded to nicotine with a relaxation under prazosin treatment, the magnitude of which was appreciably less than that in the uterine artery. Histochemical study demonstrated that perivascular nerve fibres exhibit nitric oxide synthase immunoreactivity. CONCLUSION: Canine uterine arteries are innervated by adrenergic, vasoconstrictor and nitroxidergic vasodilator nerves, and the neurogenic vasodilation is evidently more marked than that in other canine arteries, including the iliac artery.

Animals↗
PubMed1995

Involvement of nitroxidergic and noradrenergic nerves in the relaxation of dog and monkey temporal veins.

We determined involvement of nitric oxide (NO) derived from perivascular nerve in venous relaxation. In helical strips of dog superficial temporal veins contracted with prostaglandin F2 alpha (PGF2 alpha) nicotine produced a contraction, which was reversed to a relaxation by prazosin. The relaxation was partially attenuated by timolol or metoprolol. The residual relaxation was not influenced by treatment with atropine or indomethacin and by endothelium denudation but was abolished by NG-nitro-L-arginine (L-NA), a NO synthase inhibitor, and hexamethonium. L- but not D-arginine reversed the inhibition induced by L-NA. Relaxations induced by NO were not influenced by L-NA. Similar results were also obtained in relaxations induced by transmural electrical stimulation that were sensitive to tetrodotoxin (TTX). In the monkey venous strips, relaxations induced by nicotine under treatment with prazosin were reduced by timolol. The relaxation observed with combined treatment with alpha- and beta-antagonists was abolished by L-NA, and L-arginine restored the response. The presence of nerve fibers containing NO synthase immunoreactivity or NADPH diaphorase in the adventitia of dog and monkey veins was determined histologically. The findings so far obtained strongly suggest the presence of perivascular nerves that mediate venodilation via a release of NO. Contractions of the temporal vein appear to be mediated by norepinephrine (NE) released from adrenergic nerves that stimulates alpha 1-adrenoceptors, whereas relaxations are mediated by neurogenic NE, acting possibly on the beta 1-adrenoceptor subtype, in addition to NO derived from nerves.

Adrenergic alpha-Antagonists↗
PubMed1995

Relaxant responses to prostaglandin F2 alpha and E2 of isolated human uterine arteries.

We wished to determine the action of prostaglandins (PG) and to analyze pharmacologically the mechanisms of their action in isolated human uterine arteries in special reference to mediators liberated from the endothelium and subendothelial tissues. Helical strips of the human uterine artery with and without the endothelium were suspended in the Ringer-Locke solution for isometric tension recording. The relaxant response to PGF2 alpha was reversed to a contraction by cyclooxygenase inhibitors and suppressed by tranylcypromine, a PGI2 synthase inhibitor, but was not influenced by endothelium denudation. Relaxations induced by PGE2 and beraprost, a PGI2 analogue, were augmented by cyclooxygenase inhibitors and tranylcypromine but were not affected by ONO3708, an antagonist of vasoconstrictor prostanoids, and endothelium denudation. The potentiating effect of indomethacin was observed in the strips both with and without the endothelium and was antagonized by treatment with beraprost. The relaxation caused by PGF2 alpha apparently is mediated by PGI2 released from subendothelial tissues, whereas the PGE2-induced relaxation is due to the direct action on smooth muscle; the action may be eliminated by the basal release of PGI2 from subendothelial tissues.

Adult↗