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Biomedical subjects

K Shigenobu

Publications and source records attributed to K Shigenobu.

At least 181 records · Page 10Linked to original sources
PubMed1977

Synthesis and adrenergic beta-blocking activity of some 1,3-benzodioxole derivatives.

A series of 1,3-benzodioxole derivatives was synthesized. We found four compounds (2,3,10 and 11 in Table IV) to have about the same order of beta-blocking activity as that of sotalol. In addition, it is of interest that some of the compounds (2-4) were found to have hypotensive activites, although they were about one-tenth of that of hydralazine. Sotalol did not produce any change in blood pressure, and propranolol raised the blood pressure.

Adrenergic beta-Antagonists↗
PubMed1976

Antiarrhythmic action of a new beta-adrenergic blocking agent, 6-(2-hydroxy-3-isopropylaminopropyloxy)-benzothiazole succinate (KF-577), compared with that of propranolol.

The antiarrhythmic activity of a new beta-adrenergic blocking agent, 6-(2-hydroxy-3-isopropylaminopropyloxy)-benzothiazole succinate (KF-577), was compared with that of propranolol. KF-577 antagonized ouabain-induced arrhythmias in normal and bilaterally vagotomized guinea pigs; its antagonistic activity was equal to that of propranolol. Reserpinization greatly reduced ouabain intoxication and neither of the two beta-blockers produced further reduction. Aconitine-induced arrhythmias in rats were not antagonized by the two agents. In intact guinea pigs, the reduction of ouabain intoxication by both beta-blockers could not exceed that produced by simulataneous infusion of KCl, and vice versa. In isolated guinea pig atria, propranolol was about 10 times more effective than KF-577 in reducing the ouabain intoxication. The antiaarhythmic activity of KF-577 paralleled its beta-blocking activity in the isolated preparations but not in the intact animals.

Aconitine↗
PubMed1976

Valinomycin inhibition of the inward slow current of cardiac muscle.

Valinomycin (10(-6) M), a K+ ionophore and uncoupler of oxidative phosphorylation, produced pronounced shortening of the action potential plateau in young (3 day) and old (15-19 day) embryonic chick hearts and isolated perfused guinea pig hearts. The rate of rise of the action potential was usually not affected. Dimethylsulfoxide (DMSO) (2 percent), The vehicle for valinomycin, did not cause plateau shortening. In chick hearts, diminution of the plateau by valinomycin at 10(-6) M usually occurred by 1 hr; larger doses produced prominent effects within 15 min. Young embryonic hearts were more resistant to valinomycin, and 20x10(-6) M for 1-2 hr was necessary to produce a significant diminution in plateau. Several agents were able to partially relengthen the plateau shortened by valinomycin. In both young and old hearts, the resting potential was not increased by valinomycin, even though young hearts have a low resting potential because of a low K+ conductance (gK). In guinea pig, 10(-6) M valinomycin markedly shortened the plateau within 5-10 min. Contractions were abolished, i.e., the hearts became electromechanically uncoupled. When hearts were perfused with 27 mM K+ to depolarize the cells to about -40 mV to inactivate fast Na+ channels, catecholamines or methylxanthines rapidly induced slowly rising (about 10 V/sec), overshooting, plateau-like responses with accompanying contractions. Valinomycin rapidly (within 2-5 min) abolished these slow responses and contractions. Hearts perfused with 10(-6) M valinomycin or 10(-5) dinitrophenol became nearly entirely depleted of ATP within 2-10 min. These results suggest that valinomycin blocks the slow inward current indirectly through ATP depletion, the slow cation channels requiring metabolic energy. The possibility that resting gK or kinetics of changes in gK during the plateau is also affected by valinomycin cannot be excluded.

Action Potentials↗
PubMed1976

Electrophysiologically determined quinidine-like actions of a beta-adrenergic blocking agent, 1-(7-indenyloxy)-3-isopropylaminopropane-2-ol hydrochloride (YB-2).

Since 1-(7-indenyloxy)-3-isopropylaminopropane-2-ol hydrochloride (YB-2) has been reported to be a potent beta-adrenergic blocking agent with antiarrhythmic effects, the electrophysiological effects of this compound on guinea-pig and canine heart muscle were examined. YB-2 was found to have typical quinidine-like actions such as decrease in rate of rise of the action potential, prolongation of refractory period and decrease in conduction velocity.

Action Potentials↗
PubMed1975

Valinomycin shortening of action potential of embryonic chick hearts.

The effects of valinomycin, an agent known to increase the K+ conductance (gK) of lipid bilayer membranes and to be an uncoupler of oxidative phosphorylation, were examined on young (3 days old) and old (15-19 days old) embryonic chick hearts. In the old hearts, valinomycin produced pronounced shortening of the action potential plateau, and often only the spike component remained. The rate of rise of the action potential was usually not affected (slightly diminished sometimes). Addition of dimethylsulfoxide (2 percent), the vehicle for the valinomycin, did not cause shortening of the plateau. The diminution of the plateau by valinomycin at 1 mug/ml was usually obtained after incubation for 1 h; larger doses produced prominent effects within 15 min. The threshold concentration was about 0.1 mug/ml. Cooling, isoproterenol, Ba++, Sr++, and tetraethylammonium partially relengthened the plateau shortened by valinomycin. Lowering of external K+ also lengthened the plateau slightly in the presence of valinomycin. Young embryonic hearts were more resistant to valinomycin, and it was necessary to incubate with 20-40 mug/ml for 1-2 h to produce a significant diminution in plateau. In both young and old hearts, the resting potential was not increased by valinomycin, even though young hearts have a low resting potential (similar to minus 40 mV) mainly because of a low gK. These results suggest that the kinetics of the changes in gK during the action potential plateau may be more greatly affected by valinomycin than the steady-state gK of the resting membrane. In addition to such a direct effect on the sarcolemma, valinomycin could also exert an indirect effect by blocking the slow inward current through ATP depletion.

Action Potentials↗
PubMed1972

Changes in membrane properties of chick embryonic hearts during development.

The electrophysiological properties of embryonic chick hearts (ventricles) change during development; the largest changes occur between days 2 and 8. Resting potential (E(m)) and peak overshoot potential (+E(max)) increase, respectively, from -35 mv and +11 mv at day 2 to -70 mv and +28 mv at days 12-21. Action potential duration does not change significantly. Maximum rate of rise of the action potential (+V(max)) increases from about 20 v/sec at days 2-3 to 150 v/sec at days 18-21; + V(max) of young cells is not greatly increased by applied hyperpolarizing current pulses. In resting E(m) vs. log [K(+)](o) curves, the slope at high K(+) is lower in young hearts (e.g. 30 mv/decade) than the 50-60 mv/decade obtained in old hearts, but the extrapolated [K(+)](i) values (125-140 mM) are almost as high. Input resistance is much higher in young hearts (13 M ohm at day 2 vs. 4.5 M ohm at days 8-21), suggesting that the membrane resistivity (R(m)) is higher. The ratio of permeabilities, P(Na)/P(K), is high (about 0.2) in young hearts, due to a low P(K), and decreases during ontogeny (to about 0.05). The low K(+) conductance (g(K)) in young hearts accounts for the greater incidence of hyperpolarizing afterpotentials and pacemaker potentials, the lower sensitivity (with respect to loss of excitability) to elevation of [K(+)](o), and the higher chronaxie. Acetylcholine does not increase g(K) of young or old ventricular cells. The increase in (Na(+), K(+))-adenosine triphosphatase (ATPase) activity during development tends to compensate for the increase in g(K). +E(max) and + V(max) are dependent on [Na(+)](o) in both young and old hearts. However, the Na(+) channels in young hearts (2-4 days) are slow, tetrodotoxin (TTX)-insensitive, and activated-inactivated at lower E(m). In contrast, the Na(+) channels of cells in older hearts (> 8 days) are fast and TTX-sensitive, but they revert back to slow channels when placed in culture.

Acetylcholine↗