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Biomedical subjects

N Toda

Publications and source records attributed to N Toda.

At least 343 records · Page 19Linked to original sources
PubMed1978

Contractile responses of isolated dog mesenteric arteries to angiotensin I, II and III.

The addition of angiotensin (Ang-) I, II and III caused a dose-dependent contraction of helically cut strips of dog mesenteric arteries. Tachyphylaxis developed following repeated additions of angiotensins. Average median effective concentrations of Ang-I, II and III were 3.7, 0.8 and 2.5 X 10(-8) M, respectively. Contractile responses to the angiotensins were attenuated to a similar extent by Ang-II antagonists, Sar1 Ileu8 Ang-II and Sar1 Ala8 Ang-II, but were unaffected by phentolamine, methysergide and diphenhydramine. The response to Ang-I was significantly reduced by treatment with bradykinin-potentiator B, while the response to Ang-II was not influenced. It may be concluded that Ang-I, II and III produce contractions possibly by activation of same Ang-II receptors and that contractions induced by Ang-I are associated, to some extent, with a conversion to Ang-II in the arterial wall.

Angiotensin I↗
PubMed1977

Alpha-adrenergic blocking action of fentanyl on the isolated aorta of the rabbit.

The contractile response of helically-cut strips of rabbit ascending aorta to transmural electrical stimulation was attenuated in a dose-dependent manner by treatment for 20 min with fentanyl, 10(-6) to 10(-5) M. Fentanyl also shifted the dose-response curve of the contractile response of aorta to norepinephrine to the right. The response to transmural stimulation was more resistant to fentanyl than was the response to an equipotent dose of norepinephrine. The inhibitory effect of fentanyl was neither prevented nor reversed by naloxone, but was partially reversed by repeated washing of the preparations. The contractile responses to histamine and serotonin were not significantly altered by fentanyl. Treatment with fentanyl as well as phentolamine protected alpha-adrenergic receptors from persistent blockade by phenoxybenzamine. Morphine to 10(-3) M failed to influence the dose-response curve of norepinephrine significantly. It may be concluded that fentanyl reversibly blocks alpha-adrenergic receptors in a competitive manner in vascular smooth muscle, and the potency of fentanyl is approximately 1/30 that of phentolamine.

Adrenergic alpha-Antagonists↗
PubMed1977

Inhibition by Cd2+ verapamil and papaverine of Ca2+-induced contractions in isolated cerebral and peripheral arteries of the dog.

1 In helically cut strips of canine cerebral arteries exposed to Ca2+-free media and depolarized by K+, the addition of Ca2+ caused biphasic (transient and sustained) contractions, while in coronary and mesenteric arteries, the additon of Ca2+ produced a sustained contraction sometimes preceded by a slight transient contraction. 2. These Ca2+-induced contractions were attenuated by Cd2+ (50 to 100 micron) in a dose-dependent manner, the attenuation being greater in cerebral than in coronary and mesenteric arteries. The inhibitory effect of Cd2+ was prevented and partially reversed by 1 mM cysteine. 3. Verapamil and papaverine were also effective in attenuating the Ca2+-induced contrations in cerebral and peripheral arteries: susceptibility to verapamil was in the order, cerebral greater than coronary greater than mesenteric, while that to papaverine was in the order, cerebral=coronary greater than mesenteric. 4. It may be concluded that the agents that interfere with trans-membrane influxes of Ca2+ cause a greater relaxation in cerebral than in peripheral arteries, as is seen with papaverine, a non-specific vasodilator.

Animals↗
PubMed1977

Actions of bradykinin on isolated cerebral and peripheral arteries.

The addition of bradykinin (BK) caused a dose-related contraction in helical strips of canine cerebral, internal carotid, external carotid, and femoral arteries, while the peptide elicited a relaxation in canine coronary, renal, and mesenteric arteries contracted with 5+ or prostaglandin F2alpha. In contrast to canine cerebral arteries, human cerebral arteries contracted with K+ or prostaglandin relaxed with BK. Contractile responses of canine cerebral arteries to BK were not influenced by phentolamine, diphenhydramine, and methysergide, but were attenuated by aspirin and indomethacin. Contractions induced by K+ were not or only slightly inhibited by these anti-inflammatory agents. Polyphloretin phosphate failed to reduce BK-induced contractions. Relaxing effects of BK on canine coronary arterial strips were not altered by atropine, propranolol, metiamide, and aminophylline, but were inhibited by aspirin and indomethacin. Adenosine-induced relaxation was unaffected by the latter two agents. It may be concluded that adrenergic, cholinergic, histaminergic, and adenosine-related mechanisms are not involved in the genesis of BK-induced contraction and relaxation. Contractile responses of canine cerebral arteries to BK do not appear to derive from prostaglandins released, but rather from a direct action on vascular smooth muscle cells.

Animals↗
PubMed1977

[Influence of hexobendine, prenylamine and verapamil on the contractile response of isolated rabbit left atria and aortae to calcium (author's transl)].

In isolated rabbit left atria driven electrically at a frequency of 30/min, the contraction was abolished by increasing external K+ concentrations from 5.4 to 22mM. Addition of isoproterenol (10(-6)M) restored the atrial contraction and the magnitude of contractions increased by raising external concentrations of Ca++ to 4.4 and 6.6. mM. Hexobendine attenuated the magnitude of contractions restored by isoproterenol and excess Ca++ in a dose-dependent manner, as did prenylamine and verapamil. Hexobendine did not significantly influence the membrane depolarization induced by excess K+ and there was no evidence of a beta-adrenergic blocking action. In helical strips of rabbit aortae exposed to Ca++-free media and depolarized by excess K+, the addition of Ca++ caused a marked contraction. Hexobendine, prenylamine and verapamil caused a dose-related attenuation of the Ca++-induced contraction. Relative potencies of the inhibition by hexobendine, prenylamine and verapamil were 1:16.5:100. Inhibitory effects of these drugs were partially antagonized by excess Ca++. Greater attenuation of the contractile response to 25 mM K+ than the response to 2 X 10(-6)M noradrenaline was observed in preparations treated with hexobendine. It may be concluded that interference with the influx of Ca++ across cell membrane in atrial muscles and aortic smooth muscles participates in the inhibition of contractility by hexobendine.

Animals↗
PubMed1977

Cerebrovascular sensitivity to vasoconstricting agents induced by subarachnoid hemorrhage and vasospasm in dogs.

In anesthetized dogs, subarachnoid hemorrhage (SAH) was induced by the mechanical rupture of the unilateral intracranial internal carotid artery. Vasospasm was angiographically determined 24 hours and 7 days after SAH. Contractile responses to serotonin, norepinephrine, histamine, and K+ were compared in control and bleeding sides of the middle cerebral arteries removed from dogs with SAH, and from sham-operated dogs. Under sham operation and 2 hours after SAH, responses in the arteries of both sides did not appreciably differ but response was significantly less in arteries from the bleeding side as compared with the control side 24 hours and 7 days after hemorrhage. However, median effective concentrations of serotonin, histamine, and K+ were approximately the same in arteries from both sides. Vasospasm and decreased sensitivity to the vasoactive agents of middle cerebral arteries were reversed 42 days after SAH. It is thus quite likely that initiation and maintenance of post-hemorrhage vasospasm is not associated with an increase in the sensitivity of cerebral arteries to vasconstricting endogenous substances, rather the state of decreased sensitivity of cerebral arteries in contact with SAH may be instrumental in relieving prolonged vasospasm.

Animals↗
PubMed1976

Potassium-induced relaxation in isolated cerebral arteries contracted with prostaglandin F2alpha.

In helically cut strips of canine cerebral arteries exposed to 5.4 mM [K+]o and contracted with prostaglandin F2alpha, the addition of K+ in concentrations ranging from 0.5 - 5 mM caused a dose-related relaxation. The relaxing effect of K+ was potentiated reduced [K+]o and suppressed at reduced [Na+]o. Reduction of Cl- from bathing media failed to alter the effect of K+. Removal of external Ca2+ markedly attenuated the K+-induced relaxation and increase in [Ca2+]o also attenuated the relaxation. Similar relaxation was induced by K+ in cerebral arteries from other species including humans, puppies, cats and rabbits. The addition of K+ also elicited a relaxation in peripheral arteries, including coronary, femoral, mesenteric and renal, contracted with prostaglandin, but this relaxation was markedly less than in cerebral arteries. The content of Na+ in freshly excised cerebral arteries was significantly greater than that of peripheral arteries, while the content of K+ in these arteries was not significantly different. The present study provides further evidence to support the hypothesis that an electrogenic Na+ pump is involved in the genesis of K+-induced relaxation. The Na+ pump does not appear to be fully activated at normal [K+)o of 5.4 mM in cerebral arteries.]

Animals↗
PubMed1976

Regional differences in the response to nicotine in isolated canine arteries.

Helically cut strips of canine cerebral, coronary, femoral, mesenteric and renal arteries were contracted with prostaglandin F2alpha. In response to 10(-4)M nicotine, cerebral arterial strips showed a transient relaxation, which was abolished by hexamethonium, cocaine and propranolol but was not significantly influenced by sotalol and tetrodotoxin. In coronary arteries, biphasic response, relaxation followed by contraction, to 8 X 10(-4)M nicotine and contractile response to 10(-4)M nicotine were not influenced by hexamethonium, cocaine and propranolol. Initial contraction and relaxation of femoral arteries induced by nicotine were abolished by hexamethonium and cocaine. Phentolamine (2 X 10(-7)M) attenuated the contraction but not the relaxation, while sotalol (10(-5)M) reduced the relaxation without alterations in the contractile response. In mesenteric and renal arteries, the contractile response to nicotine was abolished by hexamethonium, cocaine, bretylium and phentolamine, but was attenuated only partially by tetrodotoxin. It may be concluded that nicotine exerts a relaxation in cerebral arteries by a mechanism different from the adrenergic one, and a non-specific relaxation and contraction in coronary arteries. It appears that initial contractions of femoral, mesenteric and renal arteries and also relaxation of femoral arteries in response to nicotine are associated with the release of noradrenaline; however, the mechanism of the amine release is different from that with transmural stimulation, in which the nerve action potential is involved.

Adult↗
PubMed1976

Neuromuscular blocking action of cadmium and manganese in isolated frog striated muscles.

In isolated frog sciatic nerve--gastrocnemius muscle preparations, exposure for 60 min to Cd2+ (0.1-2 mM) caused a marked attenuation of the twitch tension developed by stimulation of nerves but no or only a slight inhibition of the tension produced by direct stimulation at maximum twitch height. The inhibitory effect was partially reversed by 1 mM cysteine. In frog sartorius muscles, the addition of Cd2+ (0.1 mM) alos abolished the end-plate potential evoked by nerve stimulation but did not suppress potential changes induced by iontophoretically applied acetylcholine. The addition of Mn2+ (2 and 5 mM) attenuated the response of muscles to both direct and indirect stimulation; a greater attenuation of the latter was observed. The inhibition was not reserved by cysteine but was partially reversed by excess Ca2+. Contractile responses of frog rectus abdominis muscles to acetylcholine were not significantly affected by Cd2+ and Mn2+ but were attenuated by d-tubocurarine in a dose-dependent manner. Impulse conduction along sciatic nerves was not impaired by Cd2+ and Mn2+ but was by procaine. It appears that Cd2+ interferes with the release of acetylcholine from motor nerve terminals by reducing the transmembrane influxes of Ca2+, the influx possibly relating to SH groups of membrane constituents.

Acetylcholine↗
PubMed1976

Influence of dopamine and noradrenaline on isolated cerebral arteries of the dog.

1 Effects of dopamine and noradrenaline were compared in helically-cut strips of canine cerebral arteries. 2 Dopamine caused a greater maximal contraction than noradrenaline, although the ED50 for noradrenaline was appreciably less. The contraction induced by these amines was reversed to a relaxation by treatment with phenoxybenzamine. 3 Relaxation induced by dopamine in phenoxybenzamine-treated and prostaglandin-contracted cerebral arteries was not influenced by 1 muM propranolol, while relaxation induced by noradrenaline at low concentrations (2 muM and 10 muM) was significantly attenuated. Neither aminophylline nor atropine affected the relaxant effect of dopamine. 4 A mechanism other than beta-adrenergic, cholinergic or adenosine-related appears to be involved in the relaxation elicited by dopamine in cerebral arterial strips.

Adenosine↗
PubMed1976

Modification by temperature of the response of isolated aorta to stimulatory agents and transmural stimulation.

Contractile responses of helically-cut strips of the rabbit aorta to drugs, ions and transmural electrical stimulation were compared at different temperatures of the bathing medium, the response at 37 degrees C being taken as control. The dose-response curve of norepinephrine was moved to the right and downward by lowering the temperature from 37 to 25 degrees C and by raising temperature to 40 degrees C. Responses to transmural neural stimulation at frequencies of 5 and 20/sec were attenuated at 25 degrees C, the attenuation being greater in the response at the lower frequency. Concentrations of exogenous norepinephrine needed to produce the same magnitude of contraction as that with transmural stimulation were markedly increased by lowering the temperature to 25 degrees C. Contractile responses to norepinephrine (2 X 10(-6) M), histamine (2 X 10(-5) M) and angiotensin II (10(-7) M) were attenuated by 32-44% at 25 degrees C, whereas the responses to K+ (25 mM) and Ba++ (2 mM) were dependent on temperatures between 25 and 37 degrees C and were attenuated by 69 and 92%, respectively, at 25 degrees C. Contractures induced by Ca++ in K+-depolarized preparations exposed to Ca++-free media and also by Ba++ in preparations exposed to Ca++-free media varied directly by raising temperatures. Interference with the influx of divalent cations, such as Ca++ and Ba++, may be involved in the cold inhibition of aortic contractility.

Angiotensin II↗
PubMed1976

Age-dependence of the chronotropic response to noradrenaline, acetylcholine and transmural stimulation in isolated rabbit atria.

The chonotropic response to noradrenaline, tyramine, acetylcholine and transmural electrical stimulation was compared in atria isolated from rabbits at different stages of developmental after birth (day 2 to day 210). Pacemaker rates understeady state conditions were related inversely to days after birth; the rate in atria from rabbits at day 2 was significantly greater than that at days 10-210. The rate of neonatal rabbit atria was not significantly reduced by propranolol and the positive chontropic response to noradrenaline was not significantly reduced by propranolol and the positive chronotropic response to noradrenaline was not significantly different in atria from ages of rabbits as far as threshold concentrations for inducing tachycardia and ED50's were concerned. The maximum rate induced by noradrenaline was higher in neonatal rabbit atria than in adult rabbit atria. The effect of tyramine was approx. the same regardless of age. Increase in the pacemaker rate induced by transmural neural stimulation varied directly with age. The negative chronotropic effect of acetylcholine was greater in neonatal than in adult rabbit atria; the ED50 in the former was significantly less than in the latter. Bradycardia induced by transmural stimulation of intracardiac cholinergic nerves was related directly to age. Tachycardia in the neonatal rabbit atria may be due to electrogenic characteristics of pacemaker cells which differ from those in adult rabbit atria. Our evidence strongly suggests that the adrenergic and cholinergic nerves innervating the S-A node develop at an early postnatal stage in the rabbit.

Acetylcholine↗