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Biomedical subjects

N Toda

Publications and source records attributed to N Toda.

447 records · Page 25Linked to original sources
PubMedDate not supplied

Interactions of thromboxane A2 analogs and prostaglandins in isolated dog arteries.

Interactions of ONO3708, a thromboxane (TX) A2 analog, and epithio-methano-TXA2 (sTXA2) or prostaglandins (PGs) were investigated in helical strips of dog cerebral, coronary, renal, and mesenteric arteries. In these arterial strips sTXA2 (10(-10) to 10(-7) M) produced a dose-dependent contraction, whereas ONO3708 up to 10(-6) M failed to contract the arteries but antagonized the contractile response to sTXA2. The inhibition tended to be greater in renal arteries than in the other arteries. Contractions induced by PGF2 alpha, PGE2, and PGD2 were also suppressed by treatment with low concentrations (3 X 10(-9) and 10(-8) M) of ONO3708. The attenuations of the response to sTXA2, PGF2 alpha, PGE2, and PGD2 did not appreciably differ. Norepinephrine-induced contractions were not influenced by ONO3708 up to 2 X 10(-7) M. On the other hand, relaxant responses to PGI2 of cerebral and renal arteries were not reduced by ONO3708. Prostaglandin H2 produced a transient contraction followed by a relaxation in cerebral and renal arteries. The contractile response was abolished by 10(-7) M ONO3708, and the relaxation was potentiated. It may be concluded that ONO3708 selectively antagonizes the vasoconstrictor action of TXA2, its analogs, and PGs but does not alter the action of vasodilator PGs. At least in part, sTXA2, PGF2 alpha, PGE2, and PGD2 appear to share the same receptive site responsible for vascular contraction.

Animals↗
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Cerebroarterial relaxations mediated by nitric oxide derived from endothelium and vasodilator nerve.

Purposes of this study were to determine whether: (1) nitric oxide is involved in endothelium-dependent relaxation in helical strips of dog cerebral arteries; (2) relaxing factor distinct from NO is also involved, and (3) susceptibility to NG-nitro-L-arginine (L-NA), an NO synthase inhibitor, of the response to mediators liberating NO from the endothelium and nerve differs. Changes in isometric tension were recorded. In the strips contracted with prostaglandin F2 alpha, substance P and arginine vasopressin produced a relaxation which was abolished or reversed to a contraction by endothelium denudation. The relaxations were not influenced by indomethacin but were suppressed dose-dependently by L-NA, as was the response to nicotine that stimulates the non-adrenergic, non-cholinergic vasodilator nerve and liberates NO. The inhibitions were reversed by L- but not D-arginine. NO (acidified NaNO2)-induced relaxations were not reduced by L-NA. The inhibitory effect was greater in the responses to vasopressin than substance P; however, there was no significant difference in the response to nicotine vs. the peptides. Substance P increased the level of cyclic guanosine monophosphate (GMP) in the artery strips with the intact endothelium, the effect being abolished by endothelium denudation, L-NA and oxyhemoglobin. Relaxations caused by adenosine triphosphate (ATP) and adenosine diphosphate (ADP) were dependent partially on the endothelium. Treatment with L-NA attenuated the ATP-induced relaxation in the strips with endothelium but did not alter the response of denuded strips.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMedDate not supplied

Receptor subtypes involved in relaxation and contraction by arginine vasopressin in canine isolated short posterior ciliary arteries.

Arginine vasopressin (AVP) produced relaxations at low concentrations (10[-11] and 10[-10] M) and contractions at higher concentrations in canine ciliary arterial strips with endothelium, partially contracted with prostglandin F2alpha. The AVP-induced relaxation was abolished or reversed to a contraction by removal of the endothelium or treatment with NG-nitro-L-arginine. The effect of this antagonist was reversed by L-arginine. The relaxant response was inhibited dose-dependently by SR49059 (10[-10]-10[-9] M), [Pmp1,Tyr(Me)2]-Arg8-vasopressin (PMP-AVP) (10[-10]-10[-9] M), V1 receptor antagonists, and OPC31260 (3 x 10[-8] M), a reported V2 receptor antagonist, but not by OPC21268 (10[-7]-10[-6] M), a reported V1 antagonist. In the endothelium-denuded strips, the AVP-induced contraction was attenuated by SR49059, PMP-AVP and OPC31260, but not by OPC21268. It is concluded that AVP in low concentrations elicits intense relaxation of canine ciliary arteries, possibly due to nitric oxide synthesized in association with activation of the endothelial V1 receptor subtype. AVP-induced contractions appear to be mediated also by the V1 receptor in smooth muscle. Antagonistic selectivities of the OPC compounds to vasopressin receptor subtypes could not be seen in this particular material.

Animals↗
PubMedDate not supplied

Evidence for greater susceptibility of isolated dog cerebral arteries to Ca antagonists than peripheral arteries.

In helically-cut strips of dog cerebral, coronary and mesenteric arteries, contracted with prostaglandin (PG) F2 alpha or K+, the addition of verapamil caused a dose-related relaxation. Verapamil-induced relaxations were greater in cerebral than in the other arteries when contracted with PGF2 alpha, but did not significantly differ in the arteries contracted with K+. Similar results were obtained with diltiazem and nifedipine. The contractile response to PGF2 alpha was attenuated by pretreatment with verapamil, the ateenuation being greater in cerebral than in mesenteric arteries. Nitroglycerin and sodium nitroprusside relaxed cerebral, coronary and mesenteric arteries contracted with PGF2 alpha to a similar extent. It may be concluded that dog cerebral arteries contracted with PGF2 alpha, one of endogenous vasospastic substances, are more susceptible to agents which interfere with the influx of Ca++ across cell membranes than coronary and mesenteric arteries; these agents may thus be of value in the treatment and prophylaxis of cerebral vasopasm.

Animals↗
PubMedDate not supplied

Mechanisms of relaxant action of nicardipine, a new Ca++-antagonist, on isolated dog cerebral and mesenteric arteries.

In helically-cut strips of cerebral and mesenteric arteries contracted with prostaglandin (PG) F2 alpha, carbocyclic thromboxane A2 (cTxA2) or K+, the addition of nicardipine caused a dose-related relaxation. Nicardipine-induced relaxation was greater in cerebral than in mesenteric arteries when contracted with PGF2 alpha and cTxA2, but did not appreciably differ in the arteries contracted with K+. Cerebral arteries contracted with hemolysate and PGF2 alpha relaxed in response to nicardipine to a similar extent. The contractile response to PGF2 alpha was attenuated by pretreatment with nicardipine, the attenuation being greater in cerebral than in mesenteric arteries. Ca++-induced contractions in cerebral and mesenteric arteries previously exposed to Ca++-free media and depolarized by excess K+ were attenuated by nicardipine to a similar extent. PGF2 alpha-induced contractions of cerebral arteries exposed to Ca++-free media were attenuated by nicardipine, whereas those of mesenteric arteries were unaffected. Attenuations by nicardipine of the Ca++-induced contraction in PGF2 alpha-treated cerebral arteries were greater than those seen in mesenteric arteries. It may be concluded that nicardipine produces a greater relaxation of cerebral arteries than mesenteric arteries, possibly due to a greater inhibition of the Ca++-influx and to a decrease in the release of Ca++ from intracellular storage sites in cerebral arteries. As far as the concentrations used are concerned, nicardipine appears to attenuate the inward movement of Ca++ across cell membrane in mesenteric arterial smooth muscle, but not the release of intracellularly stored Ca++.

Animals↗
PubMedDate not supplied

Role of intrinsic arachidonate metabolites in the vascular action of erythrocyte breakdown products.

In helically-cut strips of dog basilar and mesenteric arteries, the isometric tension developed by application of ghost-free hemolysate from dog erythrocytes was recorded. The hemolysate contracted basilar arteries in a concentration-dependent fashion, the response being attenuated by treatment with either aspirin or polyphloretin phosphate, a prostaglandin antagonist. Mesenteric arteries were contracted only slightly by high concentrations of hemolysate. When the mesenteric arteries had partially been contracted with prostaglandin F2 alpha or norepinephrine, the hemolysate induced relaxations, which were abolished by aspirin in approximately half the preparations used. Studies on rat stomach strips exposed to superfusate of dog cerebral arteries showed a release of prostaglandin-like substance by the hemolysate application. It may be concluded that the hemolysate contracts basilar arteries and relaxes mesenteric arteries, mainly through prostaglandins synthesized in and released from the vascular wall. Such a mechanism may be involved in the pathogenesis of cerebral vasospasm following a subarachnoid hemorrhage.

Animals↗
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Calcium independent contraction induced by iodoacetic acid in isolated cerebral arteries.

In helically-cut strips of cerebral arteries isolated from dogs and monkeys, the addition of 1 mM iodoacetic acid (IAA) produced contractions during an early period (5 to 10 min) and also a prolonged exposure (50 to 70 min). The early contraction was abolished by exposure to Ca++-free media containing EGTA, and significantly attenuated by treatment with procaine or dantrolene. Verapamil, lidocaine, ATP and pyruvate did not inhibit the contraction. On the other hand, the late contraction was not prevented by exposure to Ca++-free, EGTA-containing media and by treatment with procaine, dantrolene, lidocaine, ATP or pyruvate. Nitroglycerin and papaverine did not relax the IAA-contracted arteries. In dog and monkey mesenteric arteries and dog coronary, renal and femoral arteries, IAA elicited contractions after a prolonged exposure, which were not inhibited by soaking the preparations in Ca++-free, EGTA-containing media. Passive tensions developed by rapid stretch in Ca++-free media did not differ in IAA-treated and control arteries. During an early period of IAA actions, Ca++ appears to be released from intracellularly stored sites in the amount sufficient to produce significant contractions in cerebral, but not in peripheral arteries. It is concluded that the involvement of Ca++ in the late contraction induced by IAA is if any minimal, and such a contraction may be associated with functional alterations induced by the metabolic inhibitor in arterial tissues other than smooth muscle.

Adenosine Triphosphate↗
PubMedDate not supplied

Responses of isolated dog cerebral and peripheral arteries to prostaglandins after application of aspirin and polyphloretin phosphate.

In helically cut strips of dog cerebral, coronary, mesenteric and femoral arteries, the contractile response to prostaglandin (PG) F2alpha, and E2, relative to contractions induced by 30 mM K+, did not appreciably differ, whereas relaxations induced by PGE1 relative to those induced by 10(-4) M papaverine were significantly different; the least in cerebral arteries and the greatest in mesenteric arteries. The relaxation of human cerebral arteries in response to PGE1 was similar to that of dog cerebral arteries. Treatment for 60 min with polyphloretin phosphate (3 X 10(-5) and 10(-4) g/ml) suppressed the contractile response to PGF2alpha and E2 but did not alter the response to 25 mM K+. The relaxing effect of PGE1 was not influenced. Aspirin (5 X 10(-5) and 2 X 10(-4) M) significantly potentiated the contractile response to PGF2alpha and E2 but did not alter the relaxation induced by PGE1. In contrast, contractions induced by serotonin were attenuated. It is concluded that dog cerebral, coronary, mesenteric and femoral arteries relaxed differently in response to PGE1. It appears that arterial responses to vasoconstricting PGs, but not to the vasodilating PG, are significantly attenuated by polyphloretin phosphate and potentiated by aspirin.

Aged↗
PubMedDate not supplied

Influence of methylene blue and oxyhemoglobin on mammalian vascular responses to sodium nitroprusside and nitroglycerin.

Vasodilatory responses to sodium nitroprusside were compared with those to nitroglycerin in helical strips of blood vessels isolated from dogs, humans, monkeys, rats and guinea-pigs. Sodium nitroprusside relaxed arterial and venous strips contracted with prostaglandin F2 alpha in a dose-related manner, as did nitroglycerin. Relaxant responses to sodium nitroprusside and nitroglycerin were significantly greater in dog coronary arteries than in the mesenteric arteries. Tachyphylaxis developed upon repeated applications of nitroglycerin but not of sodium nitroprusside. In rat and guinea-pig aortae, relaxant responses to sodium nitroprusside and nitroglycerin were markedly suppressed by treatment with methylene blue or oxyhemoglobin. In dog arteries and veins, treatment with oxyhemoglobin significantly inhibited relaxant responses to sodium nitroprusside and nitroglycerin. On the other hand, treatment with methylene blue did not inhibit responses to sodium nitroprusside but markedly suppressed those to nitroglycerin in dog blood vessels as well as in human gastroepiploic and monkey mesenteric arteries. It is concluded that dog and primate blood vessels do not develop tolerance to repeated applications of sodium nitroprusside and that sensitivity of soluble guanylate cyclase to methylene blue may differ in blood vessels from different mammals (dog and primate vs rat and guinea-pig).

Animals↗
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Age-dependent change in the response of isolated beagle cerebral arteries to vasoactive agents.

Responses to vasoactive agents were compared in helical strips of cerebral arteries from beagles of different ages (30 days, 3 months, 1 year, and 3 years old). Contractile responses to norepinephrine, serotonin, and histamine, relative to those induced by 30 mM K+, were greater in the infant (30-day-old) beagle arteries than in those from the older beagles. Angiotensin II-induced contractions did not differ in these arteries, whereas relaxations induced by the peptide, converted to contractions by indomethacin, were greater in the arteries from adult beagles than in the immature beagle arteries. Relaxations induced by nicotine, due to stimulation of vasodilator nerves, and those induced by a small amount of K+, mediated by activation of the electrogenic Na+ pump, were not dependent on age. Infant beagle cerebral arteries responded to prostacyclin (PGI2) with a greater relaxation, whereas isoproterenol produced greater relaxations in the adult beagle arteries. It may be concluded that the sensitivity or the quantity of alpha 2-adrenergic and H1-histaminergic receptors is high in the cerebral arteries of infant beagles and declines with age; the affinity of serotonergic receptors decreases with age. Biosynthesis of PGI2 in the vascular wall appears to increase with age. Functions of the vasodilator nerve innervating large cerebral arteries and of the electrogenic Na+ pump in muscle cell membranes may mature during the fetal or early postpartum period and, thereafter, are maintained unaltered.

Acetylcholine↗
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Responses to dopamine of isolated human gastroepiploic arteries.

Responses to dopamine were compared in helical strips of human gastroepiploic arteries (proximal portion) and their epiploic branches (distal portion), partially contracted with prostaglandin F2 alpha. Dopamine produced a dose-related contraction in the proximal arteries, which was reversed to a relaxation by treatment with phentolamine. On the other hand, the distal arteries responded to low concentrations of dopamine with relaxations and to high concentrations with contractions. The relaxant response was selectively suppressed by treatment with droperidol and reversed to a contraction by SCH23390, but was not influenced by domperidone and propranolol. The amine-induced relaxation was not reduced by removal of the endothelium. The distal arteries, in which dopamine elicited a relaxation, responded to norepinephrine with dose-related contractions, which were suppressed by phentolamine but were not reversed to relaxations. It may be concluded that dopamine contracts human gastroepiploic arteries of the proximal portion, due to a predominant activation of alpha-adrenoceptors, and dilates the distal arteries by acting preferentially on dopaminergic DA1-receptors, possibly residing in smooth muscle. In the distal arteries, the ability of norepinephrine to activate alpha-adrenoceptors appears to be evidently higher than that of dopamine.

Adolescent↗
PubMedDate not supplied

Comparison of the response to angiotensin II of isolated dog coronary and mesenteric arteries of proximal and distal portions.

Helically cut strips of dog coronary and mesenteric arteries of proximal and distal portions contracted in response to angiotensin (ANG) II in a dose-dependent fashion. The contractions were greater in the distal portions than in the proximal portions. Mesenteric arteries responded to the peptide with a greater contraction than coronary arteries. The peptide-induced contraction was suppressed by treatment with saralasin and was potentiated by indomethacin; magnitudes of the potentiation were similar in coronary and mesenteric arteries and in proximal and distal portions. Concentrations of TRK-100, a stable analog of PGI2, equipotent to those of PGI2 released by ANG II, estimated from dose-response curves for TRK-100 and enhancement by indomethacin of ANG II-induced contractions, did not differ in proximal and distal portions. It appears that differences in the contractile response to ANG II depend on heterogeneity in ANG II receptors responsible for the arterial contraction, but not on differences in the PGI2 generation via ANG II receptor activation.

Angiotensin II↗
PubMedDate not supplied

Different inhibition by vasodilators of coronary artery contraction.

Actions of a variety of vasodilators were compared in helical strips of the dog coronary artery, previously soaked in Ca2+-free medium under severe hypoxia. Ca2+ entry blockers, such as nifedipine and flunarizine, did not affect the PGF2 alpha-induced contraction in Ca2+-free medium, but strongly reduced the Ca2+-induced contraction under severe hypoxia in the strips stimulated by PGF2 alpha. The contraction obtained following reoxygenation was also reduced by the Ca2+ blockers. Nitroglycerin and isoproterenol inhibited the PGF2 alpha- and Ca2+-induced contractions as well as the reoxygenation-induced contraction. PGI2 methylester and TRK-100, stable analogues of PGI2, attenuated the PGF2 alpha-induced contraction in Ca2+-free medium, but not the Ca2+-induced contraction under hypoxia. PGI2 analogues inhibited the contraction due to reoxygenation to a greater extent than Ca2+ entry blockers, nitroglycerin and isoproterenol. The present study differentiated the inhibitory actions of various vasodilator agents on coronary artery contractions, possibly associated with the release of Ca2+, influx of Ca2+ through receptor-operated channel, and reoxygenation-induced facilitation of Ca2+ influx. Suppression by the vasodilators of the reoxygenation-induced coronary vasoconstriction may participate in the prophylaxis of no-reflow phenomena elicited by severe hypoxia.

Animals↗
PubMedDate not supplied

Heterogeneous responses to vasodilators of dog proximal and distal middle cerebral arteries.

Responses to various vasodilators were compared in helical strips of proximal and distal middle cerebral arteries isolated from the same dogs, which were partially precontracted with prostaglandin (PG) F2 alpha or K+. Nicotine-induced relaxations, selectively blocked by hexamethonium, were greater in the proximal than in the distal portion, whereas K+ (5 mM)-induced relaxations, reversed to contractions by ouabain, were greater in the distal portion. Angiotensin II and PGI2 relaxed distal middle cerebral arteries to a greater extent; the difference in relaxations induced by the octapeptide in large and small arteries was more evident. Relaxations induced by isoproterenol and adenosine were greater in distal arteries; in contrast, those induced by nitroglycerin were greater in proximal arteries. Acetylcholine and verapamil relaxed the arteries of both portions to a similar extent. It may be concluded that proximal middle cerebral artery functions are regulated by dilator nerves more intensely than the distal artery functions, and the electrogenic Na+ pump in cell membrane of distal middle cerebral arteries leaves more room for being activated under the experimental conditions used. Angiotensin II appears to liberate more PGI2 from the distal cerebral arteries.

Acetylcholine↗