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Biomedical subjects

K Shigenobu

Publications and source records attributed to K Shigenobu.

At least 163 records · Page 9Linked to original sources
PubMed1984

Possible role of endothelium in the vasodilator response of rat thoracic aorta to platelet activating factor (PAF).

As the endothelium has an important role in the vasodilating effect of acetylcholine, we investigated the possible role of the endothelium in the vasodilating effect of platelet activating factor (PAF). Experiments were done on spirally cut rat thoracic aorta either containing or denuded of endothelial cells. It was demonstrated that relaxation by PAF and acetylcholine of pre-contracted strips required the presence of endothelial cells. The results strongly suggested the possible involvement of endothelium in the vasodilation produced by PAF as well as by ACh.

Acetylcholine↗
PubMed1984

Effects of hypoxia and reoxygenation on tissue ATP level and electrical and mechanical function of isolated guinea pig ventricular muscles.

The myocardial ATP level in guinea pig ventricular muscles was determined during hypoxia and reoxygenation and compared with the cardiac electrical and mechanical function. The action potential duration (APD), contractile force (CF) and tissue ATP level were depressed gradually depending on the N2 concentration in the medium. Time course studies revealed that the membrane electrical activity and the ATP content did not show parallel evolution, although changes in CF coincided with changes in ATP level.

Action Potentials↗
PubMed1983

Synthesis and antihypertensive activity of stereoisomers of 4-piperidyl-1,3-dihydro-2-oxo-2H-benzimidazoles. Enhanced potencies of (+) isomers.

To elucidate the relationship between the pharmacological activity and stereochemical structure, we resolved 1-[2-(3-,4,5-trimethoxyphenyl)-2-hydroxy-1-methylethyl]-4-(1,3-dihydro-2-oxo-2H -benzimidazol-1-yl)piperidine (1 and 2) and 1-[2-(3,4-dimethoxyphenyl)-2-hydroxy-1-methylethyl]-4-(1,3-dihydro-2-oxo-2H-benzimidazol-yl)piperidine (3), which produced hypotensive effects mainly through their alpha-blocking actions. Threo isomers 1 and 3 were resolved via diastereomeric carbamates. Erythro isomer 2 was obtained by an oxidation and reduction sequence from optically active 1. No significant difference was found between the pharmacological activities of the threo and erythro isomers of the corresponding compounds. However, a clear difference was found between the pharmacological activities of the optical isomers. Difference was most clearly shown in the hypotensive actions of normotensive rats and in alpha-adrenergic blocking activities of isolated rat vas deferens. In these actions, (+) isomers were always more potent than the corresponding (-) isomers.

Animals↗
PubMed1983

Studies on the hypotensive effects of platelet activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) in rats, guinea pigs, rabbits, and dogs.

Platelet activating factor (PAF) showed profound and long-lasting hypotensive effects in normotensive and spontaneously hypertensive rats, guinea pigs, rabbits and dogs. Sensitivity to PAF was different among the animal species. The magnitude and duration of the hypotensive effect was dose-dependent. Pharmacological studies suggested that the hypotensive action was unlikely to be caused by the actions on the central or autonomic nervous systems but seemed to be mainly due to some direct action(s) on the peripheral blood vessels.

Animals↗
PubMed1983

Hypotensive action of a new benzimidazolinone derivative, threo-1-(2-hydroxy-2-(3,4,5-trimethoxyphenyl)-1-methylethyl)-4-(1,3-dihydro-2H-benzimidazol-2-one-1-yl)piperidine (KF-4942): prazosin-like mode of action.

Among a series of benzimidazolinone derivatives, KF-4942 was examined on its mode of hypotensive action. It was found that KF-4942 was a potent hypotensive agent, and that the hypotension was produced mostly by alpha-adrenergic blockade. Alpha-adrenergic blocking action of KF-4942 was suggested to be selective to the postsynaptic receptor. Thus, KF-4942 was concluded to be an agent with properties similar to prazosin.

Adrenergic alpha-Antagonists↗
PubMed1982

Postjunctional supersensitivity in young rat heart produced by immunological and chemical sympathectomy.

Postnatal changes in sensitivity to norepinephrine (NE) were studied in normal and sympathectomized rat hearts. The sensitivity of left atria to NE was highest at birth, after which it declined, reaching the adult level by 2 weeks of age. Developmental changes in NE sensitivity of the left atria seemed to be related to the density of sympathetic innervation, and the high sensitivity at birth was most likely due to the lack or immaturity of the uptake function of the nerve endings. In contrast to the atria, right ventricular papillary muscle did not change in NE sensitivity with age. Immunological and chemical sympathectomy was performed by repetitive administration of antiserum to nerve growth factor and 6-hydroxydopamine, respectively. Both atria and papillary muscles from immunologically and chemically sympathectomized rats were supersensitive to NE at all ages tested. Inasmuch as the supersensitivity to NE was most marked at the 4th week of age, atria of this age were used for the study on the mechanisms of supersensitivity. Left atria from sympathectomized 4-week-old animals were also supersensitive to isoproterenol and phenylephrine. Because isoproterenol and phenylephrine are not taken up into sympathetic nerve endings, it was concluded that the postjunctional mechanisms were involved in the genesis of the denervation supersensitivity of left atria.

Animals↗
PubMed1981

Effects of hypoxia and metabolic inhibitors on the electrical and mechanical activities of isolated guinea pig papillary muscles.

Electrical and mechanical activities of the isolated guinea pig papillary muscle were measured simultaneously, and the effects of various degrees of hypoxia and metabolic inhibitors were examined. Hypoxia selectively diminished the action potential duration (APD) dependently upon the degree of hypoxia with little affecting the other parameters of the action potential. Hypoxia concomitantly depressed the contractile force (CF), but the decrease in CF always preceded the decrease in APD; thus, the complete excitation-contraction uncoupling was sometimes observed. Metabolic inhibitors (dinitrophenol, DNP and monoiodoacetic acid, IAA) produced qualitatively the same changes in the electrical and mechanical activities. However, DNP mimicked hypoxia better than IAA which produced rather parallel decreases in CF and APD. The slow response action potential (elicited after inactivation of the excitatory fast Na system of the membrane) was completely blocked by hypoxia and metabolic inhibitors, which was partially restored by isoproterenol, histamine and tetraethylammonium. When isoproterenol was present in the bathing solution, the decreases in CF and APD produced by hypoxia were accelerated, but ATP and propranolol did not significantly modify the hypoxically induced changes.

2,4-Dinitrophenol↗
PubMed1981

Lack of parallelism between the positive inotropic effects of various cardiac stimulants and their activities to produce the slow channels in the depolarized myocardium.

Positive inotropic actions in the normal guinea pig cardiac muscle and the activities required to produce electrical and mechanical responses in the depolarized muscle were examined using epinephrine, dopamine, metanephrine, aminophylline, histamine, serotonin, tyramine, tetraethylammonium (TEA), tetramethylammonium (TMA), and X-537A, a calcium ionophore. In the normal cardiac muscle, histamine produced the greatest positive inotropic action, followed by epinephrine, dopamine and TEA. In the cardiac muscle made inexcitable by the elevated potassium (30 mM), all of the agents tested produced electrical and mechanical responses. Aminophylline was the most potent in the activity to produce the mechanical response in the depolarized muscle; the potencies of histamine, dopamine, X-537A, epinephrine and TEA were much the same. From these results, it was concluded that the positive inotropic effects of the cardiac stimulants are not produced solely through the mechanisms related to the slow channels, but that other mechanisms must be involved in the normal condition where the fast sodium channels are functioning.

Aminophylline↗
PubMed1980

Changes in sensitivity to histamine of guinea pig cardiac muscles during postnatal development.

Histamine stimulates the heart by interacting with cardiac histamine receptors. We investigated the postnatal changes in histamine sensitivity with spontaneously beating right atria and electrically driven left atria and right ventricular papillary muscles from 0-, 5-, and 10-day-old and adult guinea pigs. The positive chronotropic response to histamine in right atria was antagonized by cimetidine but not by chlorpheniramine at any age. Chlorpheniramine did not antagonize the positive inotropic effect of histamine and 2-(2-pyridyl)ethylamine in the immature left atria but it blocked the positive inotropic effect in the adult; cimetidine had no effect. The positive inotropic effect of histamine in right ventricular muscles was not affected by chlorpheniramine in immature right ventricular muscles but was antagonized in the adult. These results suggest that, in immature left atria and right ventricular muscles, there is no H1-receptor system mediating the positive inotropic effect of histamine and that, as age advances, this system begins to mediate the positive inotropic effect. In immature left atria, non-H1 and non-H2 receptors exist and mediate the positive inotropic effect of histamine.

Animals↗
PubMed1980

Negative chronotropic effect of dibutyryl cyclic AMP on the cultured chick embryonic heart cells and the prolongation of the action potential duration.

It was shown that there were clear differences between the effects of norepinephrine and dibutyryl cyclic AMP on the cultured chick embryonic heart cells. Norepinephrine and dibutyryl cyclic AMP was applied to the cultured chick embryonic heart cells, and the changes in the beating rate and the action potential configuration were examined. Norepinephrine increased the beating rate, but dibutyryl cyclic AMP produced the significant negative chronotropic effect. Norepinephrine increased the slope of the diastolic depolarization with little affecting the duration of the action potential. In contrast, dibutyryl cyclic AMP significantly prolonged the action potential duration without changing the slope of the diastolic depolarization. Thus, it was shown that dibutyryl cyclic AMP did not always produce the positive chronotropism, and it was suggested that the negative chronotropism on the cultured chick embryonic heart cells was related to the prolongation of the action potential duration.

Action Potentials↗
PubMed1980

Cardiotonic effect of phthalazinol (EG-626) in the isolated guinea pig by myocardium: mechanical and electrophysiological study.

EG-626, 7-ethoxycarbonyl-6, 8-dimethyl-4-hydroxymethyl-1 (2H)-phthalazinone, was found to be a considerably potent cardiotonic agent. It produced both the positive chronotropic and inotropic actions in the guinea pig heart muscle. Positive inotropic action of isoproterenol was potentiated by EG-626 at the concentration which did not produce a substantial positive inotropic action by itself. Cardiac action potential was not modified by EG-626 at concentrations sufficient to produce positive inotropic actions. EG-626 has a strong activity to produce slow responses in the depolarized myocardium, indicating that it can increase the density of the slow channels. The possibility was shown that the increase in the density of the slow channel may play an important role in the positive inotropic action of EG-626. The increase in the intracellular cyclic AMP due to the phosphodiesterase inhibition is tentatively most likely to be the cause of the EG-626 induced in the density of the slow channels.

Adrenergic alpha-Agonists↗
PubMed1980

Electrophysiological effects of a new antiarrhythmic agent, lorcainide, on the isolated cardiac muscle fiber as compared with disopyramide.

Electrophysiological effects of a new antiarrhythmic agent, lorcainide, were studied in the isolated guinea pig ventricular myocardium and were compared with those of disopyramide; some of the experiments were also made by using the canine ventricular myocardium. Both lorcainide and disopyramide selectively depressed the maximum rate of rise of the action potential with little effect on the resting and overshooting potential. The action potential duration tended to be shortened slightly, and the prolongation of the refractory period produced by these agents was only slight. Both agents did not produce the substantial modification of the slow response produced by isoproterenol in the depolarized muscle at the concentrations enough to depress the maximum rate of rise of the action potential. Both agents also produced the marked depression of the rate of the action potential of the canine ventricular muscle, and the conduction velocity measured in the canine false tendon was markedly decreased by both agents. It was concluded that both lorcainide and disopyramide are typical Class I agents according to the classification proposed by Vaughan Williams and that lorcainide is about 10 times (at least 3 times) more potent than disopyramide in this respect.

Action Potentials↗