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Biomedical subjects

N Toda

Publications and source records attributed to N Toda.

At least 217 records · Page 12Linked to original sources
PubMed1989

Endothelium-dependent and -independent mechanisms of action of acetylcholine in monkey and dog isolated arteries.

In helical strips of monkey coronary and mesenteric arteries and dog mesenteric arteries partially contracted with prostaglandin (PG)F2 alpha, the mechanism of action of acetylcholine (ACh) has been analyzed by the use of pharmacological antagonists and by the endothelium-derived relaxing factor (EDRF) bioassay and the 6-keto PGF1 alpha radioimmunoassay. In conclusion, ACh releases vasodilator substance(s) from endothelium (EDRF) and also PGs from subendothelial tissues. Vasoconstrictor PGs appear to counteract the dilator action of EDRF in monkey coronary arteries, whereas vasodilator PG, possibly PGI2, appears to facilitate the relaxation caused by EDRF in monkey and dog mesenteric arteries.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Prolonged exposure to oxyhemoglobin modifies the response of isolated dog middle cerebral arteries to vasoactive substances.

We exposed helical strips of dog middle cerebral arteries to oxyhemoglobin for 5 hours, rinsed them with bathing medium, and stored them overnight; we compared the responses of strips thus treated with the responses of strips without oxyhemoglobin treatment. Relaxation induced by nicotine was abolished by hexamethonium and was markedly inhibited after exposure to oxyhemoglobin. A low concentration of KCl (5 mM) elicited relaxation that was abolished by ouabain and significantly reduced by oxyhemoglobin. Endothelium-dependent relaxation caused by calcium ionophore A23187 was attenuated, and that caused by substance P was reversed to contraction after exposure to oxyhemoglobin. Contraction elicited by substance P also depended on endothelium and was abolished by indomethacin. Relaxation induced by TRK-100, a stable analogue of prostaglandin I2, was moderately attenuated by oxyhemoglobin. On the other hand, concentration-dependent relaxation induced by papaverine and contractile responses to KCl, serotonin, and prostaglandin F2 alpha were not affected by oxyhemoglobin. Our results indicate that vasodilations mediated by vasodilator nerves, the electrogenic sodium pump, endothelium-derived relaxing factor, and prostaglandin I2 were impaired in dog cerebral arteries exposed to oxyhemoglobin. After exposure to oxyhemoglobin, vascular endothelium appears to participate in cerebroarterial contraction via a release of vasoconstrictor prostaglandins. These actions of oxyhemoglobin may be involved in the genesis of cerebral vasospasm after subarachnoid hemorrhage.

Animals↗
PubMed1989

[Vasodilator actions of felodipine, a new Ca2+ entry blocker].

Felodipine [ethylmethyl 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5- pyridinedicarboxylate], a new Ca2+ entry blocker, relaxed isolated canine arteries and veins precontracted with prostaglandin (PG) F2 alpha, in a concentration-dependent manner. Felodipine dilated cerebral arteries predominantly over the other arteries. Relaxations by felodipine, in low concentrations, were greater in mesenteric vein strips than in mesenteric artery strips isolated from the same dogs. The inhibitory effect of felodipine in high concentrations (10(-7)M or higher) were not reversed by repeated washing. In coronary arteries exposed to Ca2+-free media under anoxia, PGF2 alpha and Ca2+ produced persistent contractions. Reoxygenation from anoxia elicited an additional contraction. Felodipine did not affect PGF2 alpha-induced contraction in Ca2+-free media, but significantly reduced the contractions caused by Ca2+ and reoxygenation. These findings suggest that felodipine is a potent, long-acting Ca2+ entry blocker with characteristics such as a greater action on cerebral arteries and mesenteric veins than coronary and mesenteric arteries.

Animals↗
PubMed1989

Role of endothelium in the response to prostaglandin H2 in isolated dog arteries.

Prostaglandin (PG) H2 produced a transient contraction followed by a relaxation in helical strips of dog coronary, mesenteric and renal arteries contracted with PGF2 alpha. The contraction was in the order of mesenteric greater than renal greater than coronary artery. Removal of endothelium abolished the contraction in these arteries and significantly potentiated the relaxation only in mesenteric arteries. The relaxation was greater in mesenteric arteries than in renal and coronary arteries, denuded of endothelium. PGI2-induced relaxations were not influenced by endothelium denudation. In the arteries contracted with K+, PGH2-induced relaxations were attenuated, compared to those contracted with PGF2 alpha. Treatment with ONO3708, an antagonist of vasoconstrictor PGs, abolished the PGH2-induced contraction and potentiated the relaxation in the K+-contracted arteries. The relaxant response was suppressed by diphloretin phosphate, a PG receptor antagonist, as was the response to PGI2. PGH2-induced contractions in dog coronary, mesenteric and renal arteries would be due to vasoconstrictor PGs produced preferentially in the endothelium. However, production of PGI2 from PGH2 in endothelial and subendothelial tissues do not appear to differ.

Animals↗
PubMed1989

Vasodilator actions of flunarizine in isolated dog cerebral and extracerebral arteries.

Flunarizine relaxed isolated canine arteries precontracted with prostaglandin (PG) F2 alpha, epithio-methano-thromboxane A2 and K+; the relaxation was in the order of cerebral greater than renal greater than mesenteric = coronary arteries, when contracted with PGF2 alpha or the thromboxane A2 analogue. Flunarizine-induced relaxation was unaffected by treatment with atropine, propranolol, cimetidine, cimetidine, chlorpheniramine, aminophylline and indomethacin, and by removal of endothelium. Under normoxia, flunarizine attenuated contractions elicited by Ca2+ in the K+-stimulated cerebral and mesenteric arteries that had been previously exposed to Ca2+-free media to a greater extent than that in PGF 2 alpha-stimulated preparations. The Ca2+-induced contraction in cerebral arteries was more sensitive to flunarizine than that in mesenteric arteries. Contractions caused by PGF2 alpha in Ca2+-free media were not influenced by flunarizine. In cerebral and mesenteric arteries that had been previously exposed to Ca2+-free media and severe hypoxia and then stimulated by PGF2 alpha and Ca2+, reoxygenation produced a persistent contraction. Flunarizine suppressed the reoxygenation induced-contraction. It is concluded that flunarizine dilates cerebral arteries predominantly over the other arteries; the vasodilatation appears to derive from an interference with the transmembrane Ca2+ influx that occurs through a voltage-dependent process and, to a lesser extent, receptor-operated channels, but not with the Ca2+ release from stored sites. Contraction induced by reoxygenation is expected to be due mainly to the transmembrane influx of Ca2+, which is also suppressed by flunarizine.

Animals↗
PubMed1989

Mechanisms of action of eperisone on isolated dog saphenous arteries and veins.

Effects of eperisone, an antispasmodic in skeletal muscle, were investigated in helical strips of dog saphenous artery and vein. Eperisone relaxed saphenous arteries and veins previously contracted with norepinephrine, serotonin, acetylcholine, K+, or Ba2+; but in contrast, it produced contractions in the blood vessels contracted with prostaglandin (PG) F2 alpha. Treatment with eperisone attenuated the contractions induced by norepinephrine and serotonin in the arteries and those by clonidine and phenylephrine in the veins. Eperisone inhibited angiotensin II-induced relaxations, mediated possibly by endogenous PGI2, but did not alter relaxations caused by exogenous PGI2. Treatment with eperisone (10(-5) M) potentiated the contractile response to electrical stimulation of adrenergic nerves; the potentiating effect was suppressed by yohimbine. The eperisone-induced contraction in PGF2 alpha-contracted arteries was inhibited by treatment with indomethacin or aspirin, although cyclooxygenase activity was not inhibited by eperisone. These results may indicate that eperisone blocks postjunctional alpha 1- and alpha 2-adrenergic, muscarinic, serotonergic receptors and prejunctional alpha 2 adrenoceptors and reduces PGI2 synthesis via a mechanism other than cyclooxygenase inhibition.

Animals↗
PubMed1989

Extraluminally applied acetylcholine and substance P on the release of EDRF.

Acetylcholine, substance P and nitroglycerin applied intra- and extraluminally to the perfused dog femoral artery segment with endothelium caused depressor responses. Endothelium denudation abolished the responses to acetylcholine and substance P. EC50 ratios of extra- versus intraluminal acetylcholine and substance P were 43 and 79, respectively, whereas those of nitroglycerin did not differ. Physostigmine potentiated the response to extraluminal acetylcholine. Acetylcholine seems to be degraded partly by cholinesterase in the arterial wall. Acetylcholine and substance P applied extraluminally are expected to reach the endothelium and release endothelium-derived relaxing factor.

Acetylcholine↗
PubMed1989

Possible involvement of 5-lipoxygenase products in the generation of endothelium-derived relaxing factor.

Acetylcholine and substance P applied to the donor tissue, dog femoral artery segments with endothelium, produced moderate relaxations of the assay tissue, endothelium-denuded dog coronary artery strips. The relaxation was attenuated markedly by treatment of the assay tissue with hydroquinone and abolished by oxyhemoglobin or methylene blue. In this bioassay system, the effect of AA861 and TMK777, new 5-lipoxygenase inhibitors, was evaluated. When the donor tissue was treated with AA861 or TMK777, the responses to acetylcholine and substance P were attenuated moderately, whereas the relaxation by nitroglycerin was not influenced by AA861. However, the inhibitors when infused just below the donor tissue did not attenuate relaxant responses to acetylcholine and substance P. Application of superoxide dismutase (SOD) to the donor tissue caused a relaxation of the assay tissue, and potentiated the relaxation by acetylcholine and substance P. AA861 and TMK777 suppressed the relaxant responses to acetylcholine and substance P, respectively, in the presence and absence of SOD to a similar extent and abolished the SOD-induced relaxation. Pyrogallol abolished the relaxation by acetylcholine, but did not inhibit the response when the donor tissue was pretreated with SOD. Therefore, it appears that AA861 and TMK777 do not degrade endothelium-derived relaxing factor (EDRF) in the perfusate via generation of superoxide anion or block the action of EDRF on vascular smooth muscle, but interfere with the synthesis and/or release of EDRF. The findings obtained so far support the idea that lipoxygenase products participate in the generation of EDRF.

Acetylcholine↗
PubMed1989

An orally active renin inhibitor: cyclohexylnorstatine-containing dipeptide (KRI-1314).

In our continuing search for low molecular weight, human renin inhibitors, a dipeptide derivative, morpholino-naphthyl-acyl-histidyl-cyclohexyl-norstatine (KRI-1314), was newly synthesized and estimated for oral effectiveness. This compound inhibited plasma renin from humans and from Japanese monkeys in vitro, with 50% inhibitory concentrations (IC50) of 4.7 x 10(-9) and 2.4 x 10(-8) mol/l, respectively. The mean blood pressure of sodium-depleted Japanese monkeys was lowered significantly after intravenous injection or oral administration of KRI-1314. The maximum reduction was attained 3 h after oral administration at a dose of 10 mg/kg. Plasma renin activity (PRA) was halved 1 h after oral administration of KRI-1314, and this inhibition persisted for more than 5 h. results suggest that KRI-1314, a potent, orally effective and long-lasting renin inhibitor, may become one of a new class of antihypertensive agent.

Administration, Oral↗
PubMed1989

[Muscle action potential following transcranial stimulation and absolute refractory time in somatosensory evoked potential in rabbits].

The purpose of this paper is to report the motor action potential (MAP) following transcranial stimulation and absolute refractory time (ART) in somatosensory evoked potential (SSEP) in normal rabbits. Twenty rabbits were used for this study. The MAP was recorded from a needle electrode that was inserted to the thoracic erector spinae muscle, quadriceps muscle and crural triceps muscle. The transcranial stimulation was applied on the motor area of the cerebrum by using a high voltage stimulator. ART was thereby investigated with the double stimuli method in SSEP. The waveform of the MAP was very similar to that of MAP evoked by the stimulation of peripheral nerve. A high degree of correlation existed between the latency of the MAP and distance from the stimulation site to the recording site. The ART was less than 40 ms and its mean value was 25.0 ms.

Action Potentials↗
PubMed1989

[Studies on motor action potentials following transcranial stimulation and somatosensory evoked potentials including absolute refractory time in experimental spinal cord injury].

The motor action potential (MAP) following transcranial stimulation and absolute refractory time (ART) in somatosensory evoked potential (SSEP) were investigated after experimental spinal cord injuries in rabbits. The thoracic cords were injured at the level of the 11th vertebrae by Allen's method. The paralysis after the trauma was classified into 4 groups depend on its severity; severe, mild, transient and non palsy group. A single transcranial stimulation evoked the double MAPs (MAP1 and MAP2) which were characteristic for the palsy groups. The amplitude of the MAP1 was greater than MAP2 in the transient palsy group, while that of the MAP1 was lower than MAP2 in both severe and mild palsy groups. The amplitude of the MAP was significantly reduced in all injured animals. There was no correlation between the amplitude or latency of the SSEP and the severity of the palsy. However, the ART of the SSEP was considerably prolonged in all injured animals regardless of the severity of the palsy.

Action Potentials↗
PubMed1988

Extraluminally applied acetylcholine and oxyhemoglobin on the release and action of EDRF.

Acetylcholine applied intra- and extraluminally to the donor tissue (dog femoral artery segment with endothelium) produced a relaxation of the bioassay tissue (coronary artery strip without endothelium). Extraluminal acetylcholine was 1/44 as potent as intraluminal acetylcholine (10(-7) M). Extraluminal treatment with oxyhemoglobin halved the relaxation caused by acetylcholine applied intraluminally. Acetylcholine and oxyhemoglobin applied extraluminally appear to be translocated to the endothelium, resulting in vasodilatation via the release of endothelium-derived relaxing factor (EDRF) and attenuation of EDRF actions, respectively.

Acetylcholine↗
PubMed1988

Modification by severe hypoxia and diltiazem of dog coronary artery contractions in vitro.

The contractions induced by prostaglandin (PG) F2 alpha and by Ca2+ in helical strips of canine coronary arteries exposed to Ca2+-free medium under severe hypoxia and stimulated by PGF2 alpha or K+ were augmented by the return to normoxia. Inhibition under hypoxia was ranked as follows: Ca2+-induced contractions in the strips stimulated by PGF2 alpha greater than Ca2+-induced contractions in the K+-depolarized strips greater than PGF2 alpha-induced contractions in the Ca2+-free medium. The inhibition of arterial contractions during severe hypoxia was not influenced by removal of the endothelium. Treatment with indomethacin attenuated the inhibitory effect of hypoxia on Ca2+-induced contractions in arteries stimulated by PGF2 alpha or serotonin but affected neither the Ca2+-induced contractions in the strips depolarized by excess K+ or the PGF2 alpha-induced contractions in Ca2+-free medium. Diltiazem attenuated the Ca2+-induced contractions in arteries stimulated by PGF2 alpha or K+ but did not attenuate the PGF2 alpha-induced contractions in the Ca2+-free medium during hypoxia or normoxia. Diltiazem also inhibited the contractions caused by re-oxygenation. In conclusion, severe hypoxia inhibited the contractions induced by Ca2+ in the presence of PGF2 alpha receptor activation more than those associated with membrane depolarization. The PGF2 alpha-induced contractions in the Ca2+-free medium (possibly due to the release of intracellularly stored Ca2+) may be relatively resistant to severe hypoxia. The hypoxia-induced inhibition of contractions due to Ca2+ in PGF2 alpha-stimulated arteries could be associated partly with the release of PGI2 but not with endothelium-derived relaxing factor(s).

Animals↗
PubMed1988

Responsiveness of isolated monkey coronary arteries contracted with alpha 1- and alpha 2-adrenoceptor agonists to diltiazem.

Diltiazem induced a concentration-dependent relaxation of monkey coronary arterial strips which were partially contracted with clonidine, phenylephrine, norepinephrine, prostaglandin F2 alpha. This relaxation occurred to a similar extent, but was significantly less than that observed in arteries contracted with K+. Contractions mediated via alpha 2-adrenoceptors do not appear to be more susceptible to diltiazem than those caused by activation of alpha 1-adrenoceptors and prostaglandin F2 alpha receptors.

Adrenergic alpha-Agonists↗
PubMed1988

Effects of sophoramine, an alkaloid from Sophora alopecuroides on isolated dog blood vessels.

In helical strips of dog mesenteric, coronary and cerebral arteries and mesenteric veins contracted with prostaglandin F2 alpha, sophoramine (10(-4) and 10(-3) M) produced a concentration-related relaxation, which was not influenced by treatment with indomethacin, atropine, aminophylline, propranolol, metoprolol, cimetidine, ouabain and methylene blue, and also not by removal of endothelium. Relaxations induced by sophoramine did not differ in strips of proximal and distal coronary arteries. Contractile responses to transmural stimulation in mesenteric arteries and veins were potentiated by treatment with sophoramine (10(-4) M). Treatment with cocaine, indomethacin, propranolol and saralasin did not alter the potentiating effect of sophoramine, whereas yohimbine, an alpha 2 adrenoceptor antagonist, attenuated it. Sophoramine did not significantly affect the contractile response to norepinephrine in mesenteric arteries and veins and the response to phenylephrine and clonidine in mesenteric veins. Sophoramine appears to non-specifically dilate dog arteries and veins and to facilitate the release of transmitter norepinephrine from adrenergic nerves via a mechanism of action on the prejunctional site sensitive to yohimbine.

Adrenergic Fibers↗
PubMed1988

Reoxygenation and calcium-induced cerebroarterial contractions as affected by vasodilator agents.

In helical strips of dog cerebral arteries exposed to Ca2+-free medium under hypoxic conditions (95% N2 and 5% CO2), prostaglandin (PG) F2 alpha produced a slight tonic contraction. The addition of Ca2+ evoked a phasic contraction followed by relaxation and a sustained contraction, and reoxygenation elicited an additional tonic contraction of moderate magnitude. When the PGF2 alpha-induced contraction was stabilized in Ca2+-free medium, reoxygenation contracted the arteries only slightly. Treatment with the stable PGI2 analogues PGI2 methylester and TRK-100 attenuated the contractions caused by PGF2 alpha and Ca2+ and abolished almost completely the reoxygenation-induced contraction. Treatment with nitroglycerin inhibited the contractions caused by PGF2 alpha and Ca2+, but did not significantly alter the contraction induced by reoxygenation. The Ca2+ entry blockers diltiazem, flunarizine, and felodipine did not alter the PGF2 alpha-induced contractions, but attenuated the contractions caused by Ca2+ and reoxygenation. The vasodilator agents used appear to interfere differently with the release of Ca2+ from intracellularly stored sites and the transmembrane Ca2+ influx through receptor-operated channels under hypoxia and normoxia. The cerebroarterial contraction caused by reoxygenation may be associated mainly with increased Ca2+ influx from receptor activation and tissue oxygenation, which is markedly suppressed by PGI2 analogues and moderately attenuated by Ca2+ entry blockers but not significantly influenced by nitroglycerin.

Animals↗
PubMed1988

Hemolysate inhibits cerebral artery relaxation.

In helical strips of dog middle cerebral arteries partially contracted with prostaglandin (PG) F2 alpha, relaxations induced by angiotensin-II, possibly mediated by PGI2, and those induced by PGH2 were reversed to a contraction or markedly reduced by treatment with hemolysate, which, however, attenuated the PGI2-induced relaxation only slightly. The relaxant response of human middle cerebral arterial strips to PGH2 was also suppressed by hemolysate. Dog and monkey middle cerebral arteries responded to transmural electrical stimulation and nicotine with transient relaxations, which were quite susceptible to tetrodotoxin and hexamethonium, respectively; the relaxations were abolished almost completely by hemolysate and methylene blue. On the other hand, the relaxant response of dog cerebral arteries to a low concentration of K+ was not influenced by hemolysate or by methylene blue, but was reversed to a contraction by treatment with ouabain. Relaxations induced by substance-P and nitroglycerin were markedly inhibited by hemolysate; removal of endothelium abolished the relaxation by substance-P, but did not influence the nitroglycerin-induced relaxation. Hemolysate may interfere with the biosynthesis of PGI2 in the vascular wall, thereby reversing the relaxation induced by angiotensin-II and PGH2 to a contraction. Relaxations induced by electrical and chemical stimulation of vasodilator nerves innervating cerebral arteries appear to be elicited by a mechanism dependent on cellular cyclic guanosine monophosphate (GMP), like that underlying the substance-P-induced and nitroglycerin-induced relaxation. These actions of hemolysate may be involved in the genesis of cerebral vasospasm after subarachnoid hemorrhage.

Angiotensin II↗