Biomedical subjects

N Toda

Publications and source records attributed to N Toda.

At least 253 records · Page 14Linked to original sources

PubMed1987

Neuroeffector function in mesenteric arteries isolated from beagles of different ages.

In helical strips of mesenteric arteries from 30-day (28-35 day), 3-month (80-110 day), 2-year (10-40 month) and 12-year (135-161 month)-old beagles, contractile responses to vasoconstrictors were compared. The responses to transmural stimulation and norepinephrine, relative to those caused by 30 mM K+, were greater in the infant beagle arteries than in those from the older beagles. Equipotent concentrations of the amine for producing the same magnitude of contraction as that evoked by 5 or 20 Hz stimulation in beagles of different ages did not differ. Treatment with 10(-9) M prazosin or 10(-8) M yohimbine attenuated the response to norepinephrine in 30-day and 12-year-old beagles to a similar extent. Contractions induced by transmural stimulation in the infant beagle arteries were potentiated slightly by 10(-9) M yohimbine and, in contrast, attenuated at 10(-8) M. On the other hand, the stimulation-evoked contraction in the senile beagle arteries was potentiated by these concentrations of yohimbine in a dose-dependent manner. Angiotensin II potentiated responses to electrical stimulation in 30-day and 12-year-old beagles to a similar extent. Contractions by angiotensin II and serotonin did not alter with age. It may be concluded that alpha adrenoceptor function reduces during an early postnatal period, but does not decline further through senescence. It appears that prejunctional, but not postjunctional, alpha-2 receptor function develops after birth, whereas pre- and postjunctional angiotensin receptors already mature in beagles until the age of 30 days.

Aging↗

PubMed1986

Human renin inhibiting dipeptide.

KRI-1177, a dipeptide containing nor-statine inhibited renin activity in human and Japanese monkey plasma to a markedly greater extent than that in dog, rabbit and rat plasma. The systemic blood pressure of anesthetized monkeys was lowered by intravenous injections of this compound which also reduced plasma renin activity and concentration of angiotensins. KRI-1177 appears to selectively inhibit primate renin activity, thereby producing hypotension.

Animals↗

PubMed1986

Responses of isolated dog blood vessels to glucagon.

The responses to glucagon were compared in helical strips of different arteries or veins isolated from dogs, and the relationship between the glucagon-induced relaxation and the intracellular cyclic AMP content in the arteries was studied. Relaxations induced by glucagon followed the order renal greater than mesenteric greater than femoral greater than cerebral = coronary arteries precontracted with PGF2 alpha. Glucagon-induced relaxations were greater in renal and mesenteric arteries than in the respective veins. Removal of the endothelium from the renal artery did not alter the magnitude of relaxations induced by glucagon nor the apparent ED50 value of glucagon. Glucagon increased the intracellular cyclic AMP content in both renal and coronary arteries, but the nucleotide increments were significantly greater in renal arteries than in coronary arteries. Isoproterenol produced significant increases in the intracellular cyclic AMP content and relaxations in renal and coronary arteries. Relaxations induced by dibutyryl cyclic AMP were greater in coronary arteries than in renal arteries. It is concluded that glucagon relaxed differently a variety of dog blood vessels, possibly by different extents of production of cellular cyclic AMP. The quantity and sensitivity of receptors for glucagon in smooth muscle cells may be heterogeneous in the vessels.

Animals↗

PubMed1986

Prejunctional and postjunctional actions of prostaglandins F2 alpha and I2 and carbocyclic thromboxane A2 in isolated dog mesenteric arteries.

Prostaglandin (PG) F2 alpha in concentrations insufficient to alter the basal tone potentiated contractile responses of helical strips of dog mesenteric arteries to transmural electrical stimulation but did not alter the responses to norepinephrine. Carbocyclic thromboxane A2 (cTxA2) potentiated the response to transmural stimulation, norepinephrine, serotonin and angiotensin II. PGI2 (up to 10(-7) M) attenuated the contraction induced by transmural stimulation, norepinephrine and serotonin. The potentiating effect of PGF2 alpha was not antagonized by diphloretin phosphate, a PG antagonist, whereas the effects of cTxA2 and PGI2 were prevented. 3H Overflow evoked by transmural stimulation in superfused arterial strips previously soaked in media containing [3H]norepinephrine was increased by PGF2 alpha but was not altered by cTxA2 and PGI2. It may be concluded that PGF2 alpha potentiates the contractile response to adrenergic nerve stimulation by increasing the release of norepinephrine, and that cTxA2 potentiates the response by increasing arterial muscle contractility, whereas PGI2 attenuates contractility. Prejunctional effects of PGs appear to be mediated by receptive sites different from those located postjunctionally.

Animals↗

PubMed1986

Vascular angiotensin converting enzyme in the development of renal hypertension.

The possible role of vascular angiotensin converting enzyme (ACE) is examined in vitro and in vivo. In helically cut strips of arteries isolated from dogs, contractions induced by angiotensin (ANG) I are suppressed by ACE inhibitor or ANG II antagonist. This indicates that vascular ACE contributes to the local formation of ANG II. In two-kidney, one-clip hypertensive rats, plasma-renin activity (PRA) rises rapidly with the elevation of blood pressure, then decreases gradually, despite sustained high blood pressure. Renin activity in the aorta also increases with the development of hypertension and then decreases in parallel with PRA. ACE activity in plasma does not change before or after the unilateral occlusion of the renal artery until after 16 weeks, whereas the enzyme activity in the aorta significantly increases. The conversion rate calculated from the pressor responses, and from the constricting effects of ANG I and ANG II, both in situ and in helically cut strips obtained from chronic hypertensive rats with increased vascular ACE activities, are significantly higher than those obtained from normotensive rats. Vascular ACE, which can effectively produce ANG II from ANG I locally, appears to play an important role in the maintenance of chronic hypertension.

Angiotensin I↗

PubMed1986

Vasodilator actions of TRK-100, a new prostaglandin I2 analogue.

TRK-100, a stable analogue of prostaglandin I2 (PGI2), relaxed isolated arteries of the dog precontracted with PGF2 alpha or K+; the relaxation was in the order of mesenteric and renal greater than coronary and femoral greater than basilar and middle cerebral arteries. The relaxation by TRK-100 was not affected by treatment with atropine, propranolol, cimetidine, aminophylline, and indomethacin, but was suppressed by diphloretin phosphate, a prostaglandin antagonist. Treatment with TRK-100 attenuated the contraction induced by PGF2 alpha and Ca2+ in mesenteric and basilar arteries previously exposed to Ca2+-free medium, but did not significantly alter the contractile response to Ca2+ in the arteries exposed to Ca2+-free medium and depolarized by excess K+. TRK-100 and nitroglycerin relaxed isolated mesenteric arteries to a similar extent; however, when continuously infused into mesenteric arteries in anaesthetized dogs, TRK-100 produced greater vasodilatation than nitroglycerin. It is concluded that TRK-100 relaxes dog mesenteric and renal arteries more than cerebral arteries; the relaxation appears to derive from interference with the release of Ca2+ from intracellular stores and with the transmembrane Ca2+ influx through a receptor-operated channel. TRK-100 may vasodilate large and small mesenteric arteries and resistance vessels to a similar extent, whereas nitroglycerin preferentially dilates the large artery.

Animals↗

PubMed1986

Alterations with age of the response to vasodilator agents in isolated mesenteric arteries of the beagle.

Responses to vasodilator agents were compared in helical strips of mesenteric beagles of different ages (30 days, 3 months, 2 years and 12 years old), precontracted with prostaglandin F2 alpha (PGF2 alpha). Relaxations induced by isoprenaline and adenosine were related inversely to age, whereas those induced by PGI2 and K+ (5 mM) did not alter with age. Acetylcholine-induced relaxations were less in the arteries from the aged (12 year old) beagles than in those from the younger beagles. Histamine-induced relaxations related directly to age between 30 days and 2 years. Acetylcholine-induced relaxation was reversed to a contraction in infant (30 day old) beagle arteries by removal of the endothelium, and significantly attenuated in the older beagle arteries. In adult (2 year old) and aged beagle arteries, removal of the endothelium attenuated the histamine-induced relaxation. Treatment with indomethacin reversed the histamine-induced relaxation to a marked contraction in aged beagle arteries. It may be concluded that responses mediated by beta-adrenoceptors and P1-purinoceptors are less in aged mesenteric arteries than in those from the younger beagles, whereas responses mediated by PGI2 receptors and the electrogenic Na+ pump do not alter with age. The release of endothelium-derived relaxing factor(s) by acetylcholine appears to be inversely related to age. However, the release of PGI2 possibly caused by histamine may be less in infant beagle mesenteric arteries than in those from the older beagles.

Acetylcholine↗

PubMed1986

Alpha-adrenoceptor subtypes and diltiazem actions in isolated human coronary arteries.

Isolated human, monkey, and dog coronary arteries treated with propranolol responded to norepinephrine with concentration-related contractions; the magnitude was in the order of human greater than monkey greater than dog arteries. Phenylephrine also contracted these arteries, whereas clonidine produced contractions only in the primate arteries. Contractile responses of human coronary arteries to norepinephrine were not influenced by removal of endothelium. Norepinephrine-induced contractions of human and monkey coronary arteries were attenuated by prazosin and yohimbine in a dose-dependent manner; however, the amine-induced contractions of dog coronary arteries were attenuated only by prazosin. Diltiazem, a Ca2+ antagonist, relaxed human and dog coronary arteries contracted with norepinephrine to a similar extent, but produced a greater relaxation in the human arteries when partially contracted with prostaglandin F2 alpha. These findings suggest that alpha 1- and alpha 2-adrenoceptors are involved in the amine-induced contraction in human and monkey coronary arteries, whereas only alpha 1-receptors are involved in dog artery contraction. Human coronary artery contractions induced by norepinephrine do not appear to be more susceptible to Ca2+ antagonists than the dog artery contractions, which does not provide evidence supporting the hypothesis that Ca2+ antagonists interfere with contractions mediated by alpha 2-receptors to a greater extent than those mediated by alpha 1-receptors in large human coronary arteries.

Adrenergic alpha-Agonists↗

PubMed1986

Vascular renin-angiotensin system in two-kidney, one clip hypertensive rats.

The possible role of the renin-angiotensin system in the maintenance of hypertension in two-kidney, one clip hypertensive rats was studied. Plasma renin activity rose rapidly and markedly in association with the elevation of blood pressure and then decreased gradually, although blood pressure remained high. Renin activity in the lung, aorta, and mesenteric artery also increased with the development of hypertension and then decreased in a way similar to that of plasma renin activity at the chronic stage of hypertension. Plasma angiotensin converting enzyme activity did not change significantly until 16 weeks after unilateral renal artery clipping, whereas vascular angiotensin converting enzyme activity significantly increased at the chronic, but not the acute, stage of hypertension. In chronically renal hypertensive rats, 1-sarcosine, 8-isoleucine angiotensin II or enalapril, an angiotensin converting enzyme inhibitor, lowered the blood pressure and enalapril also lowered the angiotensin converting enzyme activity of vascular tissues. The constrictor effect of angiotensin I was greater in isolated arteries from chronically hypertensive rats than in those from age-matched normotensive rats. These results suggest that the vascular renin-angiotensin system plays an important role in the maintenance of two-kidney, one clip hypertension. Elevated vascular angiotensin converting enzyme activity appears to increase local production of angiotensin II, which results in vasoconstriction by acting directly and indirectly through adrenergic nerves on vascular smooth muscle.

Angiotensin II↗

PubMed1986

[Vasoconstrictor responses of isolated pig coronary arteries].

In helical strips of pig coronary arteries, histamine, serotonin, acetylcholine and a stable analogue of thromboxane A2 (9, 11-epithio-11, 12-methano TXA2: s-TXA2) produced a dose-dependent contraction. The histamine-induced contraction was suppressed by treatment with chlorpheniramine, suggesting an involvement of H1 receptors. Contractile responses to serotonin were attenuated by not only ketanserin, an S2 antagonist, but also by cinanserin and methysergide. Relaxation induced by serotonin in preparations treated with high concentrations of ketanserin were inhibited by cinanserin and methysergide. Norepinephrine contracted coronary arteries treated with propranolol. Contractile responses to norepinephrine were reversed to relaxations by prazosin, which were abolished by treatment with yohimbine. Contractile responses to histamine were potentiated by treatment with low concentrations of serotonin or s-TXA2. Contractile responses to serotonin were also potentiated by low concentrations of histamine or s-TXA2. Removal of the endothelium from pig coronary arterial strips potentiated contractions induced by serotonin, histamine and norepinephrine. These results suggest that, in addition to damaged endothelium, integrating action of endogenous vasoconstrictors, including histamine, serotonin, TXA2 and norepinephrine, may play an important role in producing coronary vasospasm.

Acetylcholine↗

PubMed1986

Analysis of ouabain-induced contractions in isolated coronary arteries.

Contractile responses to ouabain in helical strips of dog and monkey coronary arteries were investigated. Ouabain (5 X 10(-8) to 5 X 10(-6) M) caused a dose-related contraction in dog and monkey arteries; the response of monkey coronary arteries was significantly greater. In dog coronary arteries, contractile responses to high concentrations of ouabain were potentiated by treatment with propranolol. In the arteries contracted with ouabain, the addition of phentolamine caused a relaxation. Contractile responses of dog coronary arteries to ouabain were markedly suppressed by exposure to Ca2+-free media or by treatment with verapamil. Reduction of external concentration of K+ or lowering the temperature of bathing media did not selectively influence the ouabain-induced contraction. These results suggest that ouabain-induced contractions of dog coronary arteries are associated mainly with an increase in the Ca2+-influx, which does not result from an inhibition of the Na+, K+-activated ATPase nor from an activation of alpha adrenoceptors by noradrenaline released from adrenergic nerves. Ouabain in high concentrations seems to liberate noradrenaline from adrenergic nerves, which preferentially activates beta adrenoceptors in dog coronary artery.

Animals↗

PubMed1986

Responsiveness to vasoconstrictor and dilator agents of senescent beagle cerebral arteries.

With advancing age from 2 to 12 years, contractions of isolated beagle cerebral arteries mediated by histamine H1 and serotonin receptors increased, whereas those induced by noradrenaline and angiotensin II did not differ. Relaxations by vasodilator substances, such as prostaglandin (PG) I2, isoproterenol, adenosine and K+ (5 mM), and by stimulation of vasodilator nerves in the adult and senescent beagle arteries did not significantly differ.

Adenosine↗

PubMed1986

Endothelium-dependent changes in the response to vasoconstrictor substances of isolated dog mesenteric veins.

In dog mesenteric vein strips, contractions induced by histamine relative to those induced by 5 mM Ba++ were potentiated by removal of endothelium. The induced contractions were potentiated by AA861, a lipoxygenase inhibitor, and methylene blue, a guanylate cyclase inhibitor, to an appreciably greater extent in the strips with endothelium than in those with damaged endothelium. Indomethacin did not potentiate the contraction induced by histamine. Cimetidine potentiated the contraction in control strips and those without endothelium to a similar extent whereas chlorpheniramine suppressed the contraction. Contractile responses to acetylcholine, norepinephrine, serotonin and prostaglandin (PG) F2 alpha were not potentiated by removal of endothelium. It may be concluded that histamine activates histaminergic receptors, possibly H1 but not H2, in endothelial cells and results in a release of vasodilator substance produced by lipoxygenase, which accumulates cellular cyclic GMP and relaxes mesenteric veins. The H1 and H2 receptors in smooth muscle cells appear to be responsible for contractions and relaxations, respectively. Acetylcholine, norepinephrine, serotonin and PGF2 alpha do not seem to release vasodilator substances from endothelium in an amount sufficient to cause significant relaxations of venous smooth muscle.

Animals↗

PubMed1986

Age-dependent changes in the response of isolated beagle coronary arteries to transmural electrical stimulation and catecholamines.

In helical strips of proximal and distal coronary arteries from beagles of different ages (30 days, 3 months and 1 and 3 years old) precontracted partially with prostaglandin F2 alpha, responses to catecholamines, transmural electrical stimulation, tyramine and acetylcholine were compared. Proximal coronary arteries from infant beagles responded to norepinephrine and epinephrine with contractions, whereas those from adult (1 and 3 years old) beagles responded with dose-related relaxations. Isoproterenol-induced relaxations were in the order of infant less than young less than adult beagle arteries. Norepinephrine produced contractions in the proximal arteries from infant beagles but relaxations in the distal arteries. Relaxations induced by norepinephrine and isoproterenol were in the order of small greater than medium greater than large-size arteries from adult beagles. Transmural stimulation and tyramine produced contractions in the infant and young beagle arteries of proximal portion but only relaxations in the adult beagle arteries. The contractions induced by transmural stimulation and norepinephrine were suppressed by prazosin but not by yohimbine. Acetylcholine produced similar magnitude of relaxations in the arteries from beagles of different ages. It may be concluded that contractions of coronary arteries mediated by alpha-1 adrenoceptors decrease with age, whereas beta receptor-mediated relaxations increase with age. Alpha-1 adrenoceptor functions appear to be in the order of large greater than medium greater than small-size coronary arteries from beagles of different ages, and beta receptor functions to be in the reverse order.

Acetylcholine↗

PubMed1986

Mechanisms of histamine-induced relaxation in isolated monkey and dog coronary arteries.

Relaxations induced by histamine in helical strips of monkey coronary arteries were attenuated either by chlorpheniramine or cimetidine; the H1 antagonist suppressed the fast component of relaxation, whereas the H2 antagonist reduced the slow component. Combined treatment with these antagonists abolished the amine-induced relaxation. The relaxation was not influenced by indomethacin; however, the fast component of relaxation was inhibited by 5, 8, 11, 14-eicosatetraynoic acid, AA861, a lipoxygenase inhibitor, and methylene blue. In the arteries treated with methylene blue, relaxations were abolished by cimetidine. Removal of the endothelium reduced the relaxation markedly or reversed the relaxation to a contraction; chlorpheniramine reversed the contraction to a relaxation. In dog coronary arterial strips, histamine-induced relaxations were not attenuated by removal of the endothelium. Cimetidine shifted the dose-response curve for histamine to the right, but chlorpheniramine did not alter the response. Indomethacin, AA861 and methylene blue failed to inhibit the relaxation. The response of monkey coronary arteries to histamine appears to be a sum of the slight, persistent contraction, the transient relaxation and the slowly developing relaxation. The transient relaxation may be mediated by H1 receptors in the endothelium, the activation of which yields relaxing factor, resulting in an increase of cellular cyclic GMP in smooth muscle. The contraction and the slow relaxation appear to be associated with H1 and H2 receptors, respectively, in smooth muscle cells. Dog coronary arterial relaxations induced by histamine may be mediated exclusively by H2 receptors in muscle cell membrane.

Animals↗

PubMed1985

Postmortem functional changes in coronary and cerebral arteries from humans and monkeys.

Contractile responses to 30 mmol . litre-1 K+ of helical strips of coronary arteries from human cadavers did not change within 5 h after death; however, they were suppressed 8 h after death. In coronary arteries from monkey cadavers, the K+-induced contractions did not significantly differ within the first 5 h, but were suppressed 12 h after death. On the other hand, K+-induced contractions were retained without deterioration in cerebral artery strips from human cadavers 20 to 24 h after death and those from monkey cadavers 8 to 16 h. Acetylcholine caused contractions of human coronary arteries, but caused only a relaxation of monkey coronaries which was abolished by rubbing off the endothelium. These responses were attenuated by no more than K+-induced contractions up to 12 h after death. Maximum contractions induced by noradrenaline, histamine and serotonin remained the same in human coronary arteries for 3 to 5 h after death. Similar magnitudes of contraction were elicited by noradrenaline in human cerebral arteries up to 20 h after death. It appears that the reactivity of human coronary arteries to K+ and other vasoconstrictor agents used is normally retained for at least 6 h after death and that of human cerebral arteries up to 24 h.

Adolescent↗

PubMed1985

Different responsiveness of prostaglandin D2-sensitive systems to prostaglandin D2 and its analogues.

Prostaglandin D2 (PGD2) and six PGD2 analogues were used to classify responsiveness of several PGD2-sensitive systems. The analogues used were 9 beta-PGD2, 5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl)hydantoin (BW245C), 17-phenyl-18,19,20-trinor-PGD2 (17-phenyl-PGD2), PGD2 amide, PGD2 N-monomethylamide and 11-keto-15 alpha-hydroxy-delta 5,9,12-prostenoic acid (9-deoxy-delta 9,12-PGD2). The PGD2-sensitive systems examined were human platelets, rat peritoneal mast cells, rabbit transverse stomach strip, guinea-pig tracheal ring chain and helical strip of the dog cerebral artery. PGD2, 9 beta-PGD2 and BW245C inhibited the aggregation of human platelets, increased adenosine 3'5'-cyclic monophosphate (cyclic AMP) in rat mast cells and relaxed the rabbit stomach strip. The rank order of potency was BW245C greater than PGD2 greater than 9 beta-PGD2. PGD2 amide and PGD2 N-monomethylamide were inactive in the former two systems but elicited relaxant activity on the rabbit stomach strip. 17-Phenyl-PGD2 was virtually inactive in the above three systems. PGD2 and 17-phenyl-PGD2 contracted the guinea-pig tracheal ring chain and the helical strip of dog cerebral arteries with almost equal potency. 9 beta-PGD2 and BW245C antagonized competitively the contractile action of PGD2. PGD2 amide and PGD2 N-monomethylamide showed weak agonistic actions in the tracheal preparation. 9-Deoxy-delta 9,12-PGD2, showing stronger growth inhibition than PGD2 on cultured tumour cells, was inactive in human platelets, rat mast cells and guinea-pig trachea, and elicited contractile response in the rabbit stomach strip. These results indicate the presence of three groups of PGD2-sensitive systems that respond differently to PGD2 and its analogues.

Animals↗

PubMed1985

The regional difference of relaxations induced by various vasodilators in isolated dog coronary and mesenteric arteries.

Relaxant responses to vasodilators, including nitroglycerin, sodium nitroprusside, prostaglandin I2 sodium salt (PGI2), prostaglandin E1 (PGE1), diltiazem hydrochloride and adenosine, were compared in helical strips of dog coronary arteries of different sizes and in coronary and mesenteric arterial strips. The relaxant responses to nitroglycerin, sodium nitroprusside, diltiazem and adenosine were significantly greater in coronary arteries than in mesenteric arteries, whereas the responses to PGI2 and PGE1 in these arteries did not significantly differ. In coronary arteries of different sizes, the relaxation induced by nitroglycerin was in the order of large greater than medium greater than small-size, while in contrast, the relaxations by adenosine, PGI2 and PGE1 were greatest in the small-size arteries and least in the large-size arteries. The relaxant responses to sodium nitroprusside and diltiazem did not differ in the coronary arteries of different sizes. Nitroglycerin, sodium nitroprusside and diltiazem appear to dilate coronary arteries more predominantly than mesenteric arteries. The preferential dilator action of PGI2 and PGE1 on distal coronary arteries, like that of adenosine, may lead more blood to re-distribute to the non-ischemic region of the heart in anginal patients.

Adenosine↗