Biomedical subjects

N Toda

Publications and source records attributed to N Toda.

At least 127 records · Page 7Linked to original sources

PubMed1994

Responses to histamine and acetylcholine in isolated monkey mesenteric veins versus arteries.

OBJECTIVE: The aim was to analyse and compare mechanisms of histamine or acetylcholine action in mesenteric venous and arterial strips obtained from Japanese monkeys. METHODS: Monkey mesenteric arterial and venous strips were suspended for isometric tension recording in modified Ringer-Locke solutions, and responses of the strips precontracted with prostaglandin F2 alpha to histamine or acetylcholine were compared. RESULTS: Histamine (2 x 10(-8) M-10(-5) M) produced a concentration related relaxation in the arteries and veins. The arterial relaxation was slightly but significantly attenuated by endothelial denudation [57.1(SEM 11.2)% inhibition at 10(-7) M, n = 14, p < 0.05] and treatment with 10(-6) M chlorpheniramine [26.7(6.7)% inhibition at 10(-7) M, n = 10, p < 0.05] or 10(-5) M methylene blue [31.5(11.2)% inhibition at 10(-7) M, n = 9, p < 0.05], and markedly suppressed by 10(-5) M cimetidine [96.8(1.2)% inhibition at 10(-7) M, n = 13, p < 0.001]. Indomethacin (10(-6) M) was without effect. On the other hand, relaxant responses to histamine of the venous strips were not influenced by endothelial denudation and treatment with chlorpheniramine or indomethacin but were abolished by treatment with cimetidine. Removal of the endothelium did not alter the venous relaxation caused by acetylcholine (10(-8) M-10(-4) M) but almost abolished the response to Ca2+ ionophore A23187 (10(-7) M) and substance P (10(-7) M). The acetylcholine induced relaxation was reversed to a contraction by indomethacin. CONCLUSIONS: Histamine-induced relaxations of monkey mesenteric arteries seem to be associated mainly with activation of the H2 receptor subtype in smooth muscle and partially mediated by relaxing factor liberated by stimulation of the H1 subtype in the endothelium, whereas the mesenteric venous relaxation seems to be due exclusively to a mediation of H2 receptors. Acetylcholine-induced relaxations of venous strips appear to be caused by vasodilator prostanoids, possibly prostaglandin I2, liberated from subendocardial tissues.

Acetylcholine↗

PubMed1994

Mechanism underlying substance P-induced relaxation in dog isolated superficial temporal arteries.

1. In helical strips of dog superficial temporal arteries with intact endothelium, substance P elicited a concentration-related relaxation with an EC50 of 2.8 (2.4-3.2) x 10(-10) M. 2. The relaxant response to the peptide in low concentrations (1-4 x 10(-10) M) sufficient to produce approximately half maximal relaxation was not inhibited by indomethacin, but was markedly suppressed by NG-nitro-L-arginine (L-NOARG), a nitric oxide (NO) synthase inhibitor, and by endothelium denudation. 3. High concentration (10(-7) M) of substance P produced marked relaxations in endothelium-intact strips. Removal of the endothelium attenuated the relaxation, and indomethacin or tranylcypromine suppressed the endothelium-independent relaxation. In indomethacin-treated strips with intact endothelium, L-NOARG attenuated but did not abolish the relaxation. The residual, L-NOARG-resistant relaxation was not significantly inhibited by ouabain, glibenclamide or tetraethylammonium. 4. Substance P (10(-7) M) increased the levels of cyclic GMP and cyclic AMP. The increase in cyclic GMP was abolished by endothelium denudation and treatment with L-NOARG, whereas the cyclic AMP increment was abolished by indomethacin. 5. Three different mechanisms may be involved in the substance P-induced relaxation: (1) an endothelium-dependent relaxation mediated by the release of NO from the endothelium, resulting in an increase of cyclic GMP (low and high concentrations of the peptide); (2) an endothelium-independent relaxation in association with cyclic AMP increment caused by prostaglandin I2 released from subendothelial tissues (high concentration), and (3) another endothelium-dependent relaxation possibly mediated by unidentified mediator(s) released from the endothelium (high concentration).

Analysis of Variance↗

PubMed1994

Human uterine arterial relaxation induced by nitroxidergic nerve stimulation.

Uterine arterial strips obtained from humans responded to nicotine with a contraction, which was abolished by prazosin. In the arteries treated with the alpha 1-receptor antagonist and partially contracted with serotonin, nicotine produced a relaxation that was not influenced by treatment with atropine or timolol and endothelium denudation but was abolished by hexamethonium, oxyhemoglobin, and NG-nitro-L-arginine (L-NNA). The inhibitory effect of L-NNA was reversed by L- but not D-arginine. Relaxations induced by nitroglycerin and nitric oxide (NO) were not affected by L-NNA but were abolished by oxyhemoglobin. Transmural electrical stimulation relaxed the arterial strips treated with prazosin; this response was abolished by L-NNA and restored by L-arginine. Histochemical study with NO synthase antiserum demonstrated the presence of immunoreactive nerve fibers in the adventitia. It may be concluded that human uterine arteries are innervated by vasodilator nerves that liberate NO as a neurotransmitter after chemical or electrical stimulation. Predominant vasoconstriction due to nerve stimulation appears to be associated with activation of alpha 1-adrenoceptors by neurogenic norepinephrine.

Adult↗

PubMed1994

Role of nitroxidergic nerve in dog retinal arterioles in vivo and arteries in vitro.

Functional role and anatomic location of nitroxidergic nerves were determined in dog retinal arteries and arterioles. Isolated retinal central arteries responded to nicotine with relaxations that were not influenced by atropine, timolol, or indomethacin and damage of the endothelium, but were abolished by hexamethonium, methylene blue, and oxyhemoglobin. The relaxation was abolished by NG-nitro-L-arginine (L-NNA), a nitric oxide (NO) synthase inhibitor, and was restored by L-arginine. Relaxations caused by NO were not affected by L-NNA. Transmural electrical stimulation at 5 Hz relaxed the strips; the relaxation was abolished by L-NNA and tetrodotoxin. In anesthetized dogs, intraarterial injections of nicotine dilated retinal arterioles in the fundus oculi. This effect was abolished by L-NNA and restored by L-arginine. Intravenous injections of L-NNA constricted retinal arterioles, the effect being prevented by hexamethonium. There were nerve bundles and fibers containing NO synthase immunoreactivity in the adventitia and media in the retinal artery. These findings are consistent with our hypothesis that NO liberated from vasodilator nerves acts as neurotransmitter in dog retinal arteries and arterioles, and the arteriolar muscle tone is regulated by vasodilator nerve activity in vivo.

Amino Acid Oxidoreductases↗

PubMed1994

Histological and functional studies on the nitroxidergic nerve innervating monkey cerebral, mesenteric and temporal arteries.

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.

Amino Acid Oxidoreductases↗

PubMed1994

Differences in adrenergic nerve and receptor function in dog internal thoracic, coronary and mesenteric arteries.

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.

Animals↗

PubMed1994

Effects of alcohol on membrane fluidity of human erythrocyte.

Membrane fluidity in human erythrocytes was measured by a spin label method using an electron spin resonance spectrometer in healthy volunteers after ingestion of alcohol (1.5 ml of whisky/kg body weight). Fluidity in the lipid bilayer closer to the hydrophilic face decreased at 30 min and 90 min, and fluidity in the hydrophobic core decreased at 90 min after ingestion of alcohol. In the same experiment, the level of thiobarbituric acid reactive substances in the serum decreased 30 min after ingestion of alcohol, and the triglyceride level increased and free fatty acid level decreased, and serum superoxide dismutase activity increased 150 min after ingestion. Furthermore, membrane fluidity in human erythrocytes was examined in patients with alcohol dependence syndrome who had not any alcohol for about 26 months. Erythrocyte membrane fluidity of patients with alcohol dependence syndrome was not different from that of healthy controls. However, erythrocyte membrane fluidity of the lipid bilayer closer to the hydrophilic face increased in patients who had concomitant liver cirrhosis compared with those who did not. These results suggest that alcohol affects temporal change of membrane fluidity in human erythrocytes.

Adult↗

PubMed1994

Neurogenic relaxations caused by nicotine in isolated cat middle cerebral arteries.

In cat middle cerebral arterial strips denuded of the endothelium, nicotine produced a relaxation that was abolished by treatment with hexamethonium. The relaxation was partially inhibited by treatment with NG-nitro-L-arginine (L-NNA), a nitric oxide (NO) synthase inhibitor, and oxyhemoglobin, an NO scavenger. The remaining relaxation in the media containing L-NNA was abolished in the strips made unresponsive to calcitonin gene-related peptide (CGRP) by its repeated application. However, this was not the case when the strips were made tachyphylaxic to vasoactive intestinal polypeptide. The nicotine-induced relaxation was also partially attenuated by pretreatment with capsaicin; the remaining relaxation was abolished by L-NNA but not by its D-enantiomer. The inhibitory effect of L-NNA was reversed by L- but not D-arginine. Histochemical study revealed that injections of ethanol into the vicinity of pterygopalatine ganglion abolished the positive staining for nicotinamide adenine dinucleotide phosphate diaphorase activity and the CGRP immunoreactivity in perivascular nerves innervating the middle cerebral artery of the ipsilateral side. The nicotine-induced relaxation in the middle cerebral artery from the ethanol-injected side was markedly inhibited compared with that from the nontreated side, whereas the relaxations induced by exogenously applied NO and CGRP were unaffected. We conclude that nicotine stimulates nicotinic receptors in nerve terminals and liberates NO or NO-like substance(s) and CGRP as neurotransmitters in cat middle cerebral arteries.

Animals↗

PubMed1993

Nitric oxide synthase-immunoreactive nerve fibers in dog cerebral and peripheral arteries.

Nitric oxide synthase (NOS)-immunoreactive fibers innervating the dog arterial wall were histochemically determined by the use of NOS antiserum. NOS-immunoreactive fibers were consistently found in every arterial wall examined. In a whole-mount preparation, NOS-positive fibers were detectable in the small pial artery having a diameter of about 100 microns as well as the proximal middle cerebral artery. Further detailed analyses in thin cryostat sections indicated that in middle cerebral, basilar, temporal, mesenteric and femoral arteries, fine NOS-positive fibers were detected in outer zones of the media in addition to many thicker fibers in the adventitia. However, in the coronary artery, many thick fibers were situated in the adventitia, and fine NOS-positive fibers were not found in the media. Injection of ethanol to the pterygopalatine ganglion markedly decreased or abolished the NOS immunoreactivity in nerve cells and fibers and abolished the innervation of NOS-positive fibers in the wall of middle cerebral artery of the ipsilateral side. Together with findings in our previous publications concerning the functional role of nitroxidergic nerve in the control of arterial tone, we conclude that perivascular nerves containing NOS are crucial in eliciting the neurally induced, NO-mediated arterial relaxation.

Amino Acid Oxidoreductases↗

PubMed1993

Interactions of nitrovasodilators and atrial natriuretic peptide in isolated dog coronary arteries.

In helical strips of dog coronary arteries contracted with prostaglandin F2 alpha, relaxant responses to atrial natriuretic peptide (ANP), nitric oxide (NO), nitroglycerin and 8-bromo cyclic GMP were markedly inhibited or abolished by treatment with a high concentration of sodium nitroprusside, whereas the responses to beraprost and papaverine were not influenced. A similar suppression of the responses to ANP, NO, and sodium nitroprusside was observed after treatment with nitroglycerin. The relaxations induced by NO and nitroglycerin were abolished by methylene blue and oxyhemoglobin, whereas the response to ANP was not influenced. The sodium nitroprusside-induced relaxation was significantly potentiated by methylene blue but was abolished by oxyhemoglobin. The increase in cyclic GMP caused by ANP and nitroglycerin was not influenced by treatment with sodium nitroprusside, despite the fact that the responses to ANP and nitroglycerin were suppressed. It can be concluded that ANP and nitroglycerin or sodium nitroprusside share the same mechanism of action on intracellular processes occurring after the synthesis of cyclic GMP in dog coronary artery smooth muscle cells and that cross-tachyphylaxis between nitroglycerin, sodium nitroprusside, and ANP in the mechanical response is not associated with an impaired production of cyclic GMP.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1993

Effects of NG-nitro-L-arginine on electrical and mechanical responses to stimulation of non-adrenergic, non-cholinergic inhibitory nerves in circular muscle of the rat gastric fundus.

The effects of L-nitroarginine (L-NNA), an inhibitor of nitric oxide (NO) synthesis, on non-adrenergic, non-cholinergic inhibitory transmission in the circular smooth muscle of the rat gastric fundus were studied. The relaxation in response to nerve stimulation in the presence of guanethidine and atropine was depressed by the application of L-NNA (10(-4) M), and the depression was reversed by the addition of L-arginine (10(-4) M). The time course of the relaxation was altered from a monophasic to biphasic one, both of which were depressed. Stimulation of non-adrenergic, non-cholinergic nerves initiated inhibitory junctional potentials (i.j.p.). In addition, slow after-hyperpolarization was observed when stimuli were applied repeatedly at frequencies higher than 0.5 Hz. L-NNA reduced the i.j.p. partially and abolished the after-hyperpolarization, indicating the partial involvement of NO in non-adrenergic, non-cholinergic inhibitory transmission. The effects of L-NNA on the nerve-mediated relaxation are thought to be due to changes in the i.j.p. and slow after-hyperpolarization.

Animals↗

PubMed1993

Mediation by nitric oxide of neurally-induced human cerebral artery relaxation.

Human cerebral artery strips relaxed in response to non-adrenergic, non-cholinergic vasodilator nerve stimulation by electrical pulses or nicotine. The relaxation response was abolished by treatment with NG-nitro-L-arginine, a nitric oxide synthase inhibitor; the inhibitory effect was reversed by L-, but not D-, arginine. Nitric oxide-induced relaxation was unaffected. These findings support the hypothesis that nitric oxide plays a crucial role, possibly as neurotransmitter, in transmitting information from vasodilator nerve to smooth muscle in human cerebral arteries.

Arginine↗

PubMed1993

Mechanisms of acetylcholine-induced relaxation in dog external and internal ophthalmic arteries.

Mechanisms underlying the relaxant response to acetylcholine (ACh) were examined in dog external (EOA) and internal ophthalmic arteries (IOA). Acetylcholine produced relaxation in EOA and IOA, partially contracted with prostaglandin (PG) F2 alpha. The relaxations induced by ACh in these arteries were not inhibited by endothelium denudation. The ACh (10(-8)-10(-5) M)-induced relaxations in EOA and IOA were abolished by treatment with atropine or indomethacin and markedly suppressed by tranylcypromine, a PGI2 synthesis inhibitor, but not influenced by hexamethonium. On the other hand, the relaxant response to the highest concentration used (10(-4) M) was partially attenuated but not abolished by treatment with atropine, indomethacin or hexamethonium. This relaxation under treatment with atropine was abolished by NG-nitro-L-arginine (L-NA), a nitric oxide synthase inhibitor, but not by indomethacin, whereas the response under treatment with hexamethonium was abolished by indomethacin, but not by L-NA. Combined treatment with indomethacin and L-NA or oxyhaemoglobin abolished the ACh (10(-4) M)-induced relaxation, or reversed it to a contraction. It may be concluded that relaxations induced by low concentrations of ACh in dog EOA and IOA are associated possibly with the release of PGI2 through activation of muscarinic receptors located in subendothelial tissues, including smooth muscle, and the relaxant response to the high concentration (10(-4) M) of ACh is mediated mainly by the release of nitric oxide through activation of nicotinic receptors in nitroxidergic nerves.

Acetylcholine↗

PubMed1993

A case of chronic pancreatitis complicated by massive pericardial and right pleural effusion.

A 42-year-old man was admitted complaining of dyspnea. Chest X-ray showed an increase in cardiac size, and echocardiography revealed a large volume of pericardial effusion. Pancreatic enzyme levels were elevated in both serum and pericardial effusion. Computed tomography and endoscopic retrograde pancreatography demonstrated a fistula connecting a pancreatic pseudocyst with the pericardium and the right pleural cavity. Massive pericardial and right pleural effusion is an extremely rare complication of chronic pancreatitis. In this case, computed tomography and endoscopic retrograde pancreatography were useful for diagnosing the fistula.

Adult↗

PubMed1993

Nitric oxide mediates, and acetylcholine modulates, neurally induced relaxation of bovine cerebral arteries.

Helical strips of bovine basilar arteries denuded of the endothelium responded to transmural electrical stimulation with frequency-dependent relaxations that were abolished or markedly attenuated by treatment with tetrodotoxin, oxyhemoglobin and Methylene Blue. Relaxations induced by vasoactive intestinal polypeptide and calcitonin gene-related peptide were not affected by oxyhemoglobin and Methylene Blue. The neurally induced relaxation was not attenuated in the artery made unresponsive to these peptides by successive application. The relaxation caused by nerve stimulation was markedly inhibited by treatment with NG-nitro-L-arginine, a nitric oxide synthase inhibitor, which did not inhibit the relaxation caused by exogenously applied nitric oxide. The inhibition was reversed by L-arginine but not by the D-enantiomer. Exogenously applied acetylcholine did not alter the tone of endothelium-denuded arteries. Neurally induced relaxations were attenuated by treatment with acetylcholine and physostigmine and were significantly potentiated by atropine. It may be concluded that the relaxation induced by nerve stimulation is mediated by nitric oxide, but not by vasoactive intestinal polypeptide or calcitonin gene-related peptide, derived from vasodilator nerves innervating the bovine basilar artery, and the nerve function is inhibited prejunctionally via muscarinic receptor activation by acetylcholine released from cholinergic nerves but is not influenced by vasoactive intestinal polypeptide.

Acetylcholine↗

PubMed1993

Mechanisms of endothelium-dependent responses to vasoactive agents in isolated porcine coronary arteries.

In isolated porcine coronary arteries, acetylcholine elicited contractions that were potentiated by endothelium denudation. In endothelium-intact strips, the contraction deteriorated by repeated trials and was reversed to a relaxation. NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthesis inhibitor, abolished the relaxation or reversed it to a contraction. Endothelium-dependent relaxations caused by serotonin were also reversed to a contraction by treatment with L-NA. Relaxations caused by substance P were dependent on the endothelium and were abolished by oxyhemoglobin; however, L-NA did not completely abolish the relaxation. It may be concluded that porcine coronary arteries respond to acetylcholine with contractions by a direct action on smooth muscle that are minimized by stimulated release of NO from the endothelium. It appears that the relaxation caused by serotonin is due to NO released from the endothelium, whereas the substance P-induced relaxation is associated mainly with endothelium-derived NO produced by NO synthase sensitive to L-NA and also with NO produced via a L-NA-resistant process or via a pathway distinct from that through NO synthase.

Acetylcholine↗

PubMed1993

Responses to perivascular nerve stimulation of distal temporal arteries from dogs and monkeys.

In helical strips of dog distal superficial temporal artery denuded of endothelium and partially contracted with prostaglandin F2 alpha (PGF2 alpha), nicotine produced a moderate relaxation preceded by no contraction or a slight contraction. The contraction was less than that observed in proximal arterial strips obtained from the same dogs and was abolished by alpha-adrenoceptor antagonists. Relaxations under alpha-receptor blockade were greater in the distal than in the proximal arteries. Treatment with NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor, abolished the relaxation caused by nicotine and transmural electrical stimulation (5 Hz for 40 s), the response being reversed by L- but not by D-arginine. In monkey temporal arteries of the distal and proximal portions treated with alpha-antagonists, nicotine produced similar magnitudes of relaxation, which were abolished by treatment with the NO synthase inhibitor. Vasodilator nerves appear to play an important role in regulation of small arterial tone; noradrenergic vasoconstrictor function is less and vasodilator nerve function is more evident in dog distal arteries than in dog proximal arteries. The neurally induced relaxation in dog and monkey distal temporal arteries is postulated to be mediated by NO derived from nerves.

Adrenergic alpha-Antagonists↗

PubMed1993

Neural mechanism underlying basilar arterial constriction by intracisternal L-NNA in anesthetized dogs.

Basilar arterial diameters were angiographically measured in anesthetized dogs in which systemic blood pressure and heart rate were also monitored. Injections of NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor, into the cisterna magna produced a significant, persistent decrease in arterial diameter, the effect being reversed by intracisternal injections of L-arginine. The vasoconstrictor effect of L-NNA was diminished in dogs treated with hexamethonium. On the other hand, treatment with phentolamine in a dose sufficient to lower blood pressure to a level similar to that attained with hexamethonium did not inhibit, but rather potentiated, the effect of intracisternal L-NNA. Nicotine injected into the vertebral artery significantly dilated the basilar artery. The effect was abolished by treatment with L-NNA applied intracisternally, the inhibition being reversed by the addition of L-arginine. Systemic blood pressure and heart rate were not altered by intracisternally applied L-NNA and L-arginine. These findings support the hypothesis that basilar arterial constriction caused by intracisternal L-NNA is associated with a suppression of NO synthesis in nitroxidergic nerves innervating the cerebroarterial wall rather than an elimination of basal release of NO from the endothelium. Functional importance of nitroxidergic vasodilator innervation in cerebral arteries in vivo is thus clarified.

Anesthesia↗