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Biomedical subjects

N Taira

Publications and source records attributed to N Taira.

At least 181 records · Page 10Linked to original sources
PubMed1984

Nicorandil releases acetylcholine-induced sustained coronary arterial constriction in monkeys and baboons.

The spasmolytic action of nicorandil on coronary circulation was investigated in 3 Japanese monkeys (Macaca fuscata), 1 rhesus monkey (Macaca mulatta), and 1 anubis baboon (Papio anubis) anesthetized with pentobarbital. The arterial bed of the left anterior descending coronary artery (LAD) was perfused with autologous arterial blood at a constant pressure close to systolic arterial blood pressure. Single injections of nicorandil (10-300 micrograms) into the LAD produced a dose-dependent increase in blood flow without affecting either systemic arterial blood pressure or heart rate. With continuous infusion of acetylcholine into the LAD, the LAD flow decreased to nearly half the basal level, indicating sustained coronary arterial constriction. Under these conditions intra-LAD nicorandil increased the LAD flow virtually to the same extent as before acetylcholine-infusion. These effects of nicorandil resemble those of the Ca++-antagonists, diltiazem and nifedipine, but differ from those of nitroglycerin, which is less effective during sustained coronary arterial constriction. The results imply that nicorandil may be as effective as Ca++-antagonists in the treatment of vasospastic angina.

Acetylcholine↗
PubMed1984

Improvement of cardiac performance by AR-L 115 BS, a new cardiotonic drug, in the experimental failing dog heart.

The cardiotonic effect of AR-L 115 BS was assessed in 5 dog heart-lung preparations in which cardiac function had been severely depressed by pentobarbital. AR-L 115 BS in doses of 1-60 mg improved cardiac function in a dose-dependent manner and at 30 and 60 mg improved it beyond control values. These doses of AR-L 115 BS, however, produced neither a significant increase in heart rate nor arrhythmias. The results indicate that the drug would be of use in the treatment of heart failure.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1984

Comparison of the cardiovascular and biochemical profiles of a new positive inotropic drug, AR-L 115 BS, with those of theophylline.

Cardiac and coronary vasodilator effects of AR-L 115 BS and theophylline were compared in isolated, blood-perfused papillary muscle, sino-atrial (SA) node, and atrioventricular (AV) node preparations of dogs. Furthermore, the inhibitory effects of both drugs on crude cyclic AMP phosphodiesterase (PDE) prepared from the dog heart ventricle were examined. In the blood-perfused dog-heart preparations, AR-L 115 BS (3 micrograms-1 mg) and theophylline (3 micrograms-1 mg) were injected intra-arterially. Both drugs increased sinus rate and force of contraction and rate of automaticity of the papillary muscle, and decreased AV nodal conduction time in the respective preparations. The 2 drugs both increased blood flow. However, AR-L 115 BS was far more selective for inotropy than for chronotropy as compared with theophylline. AR-L 115 BS was also more selective for inotropy than for coronary blood flow as compared with theophylline, whereas the latter had the opposite selectivity. Both drugs were less effective on ventricular automaticity. Both drugs (0.3-3 mM) inhibited PDE activity; however, AR-L 115 BS was less effective than theophylline in this respect, although the former was about 3 times as potent as the latter in producing a positive inotropic effect. The present results suggest that unknown mechanisms other than PDE-inhibition greatly contribute to the positive inotropic effect of AR-L 115 BS.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1984

Mode and mechanism of action of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)- quinolinone (OPC-8212), a novel positive inotropic drug, on the dog heart.

Mode and mechanism of action of 3,4-dihydro-6-[4-(3,4- dimethoxybenzoyl )-1-piperazinyl]-2(1H)- qu inolinone ( OPC -8212) were investigated exclusively on dogs both in vivo and in vitro. When assessed by intra-arterial administration in isolated, blood-perfused papillary muscle, sinoatrial node and atrioventricular (AV) node preparations, OPC -8212 produced a positive inotropic effect scarcely causing either positive or negative chronotropic and coronary vasodilator effects. AV nodal conduction was slightly facilitated with OPC -8212, whereas ventricular automaticity was rather suppressed. No arrhythmias were produced. Thus, OPC -8212 is highly specific for force. In heart-lung preparations OPC -8212 improved cardiac function depressed with pentobarbital, and caused bradycardia. In trabecular muscles of the right ventricle (hereafter simply called ventricular muscles) OPC -8212 produced a concentration-dependent positive inotropic effect in the presence of the beta 1-adrenoceptor antagonist, atenolol. This indicates that the positive inotropic effect of OPC -8212 is not mediated through a beta-adrenoceptor mechanism. In ventricular muscles OPC -8212 increased plateau potentials of normal action potentials in the presence of atenolol. In K+-depolarized ventricular muscles OPC -8212 increased overshoot potentials and durations of slow response action potentials in the presence of atenolol. These suggest an increase in the slow inward current to underlie the positive inotropic effect of OPC -8212. In ventricular muscles OPC -8212 shortened total duration of contraction and time to peak tension in the presence of atenolol. In ventricular muscles OPC -8212 increased force of contraction and intracellular concentrations of cyclic AMP in a parallel way in time course in the presence of atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Selectivity of alinidine, a bradycardic agent, for SA nodal automaticity versus other cardiac activities in isolated, blood-perfused dog-heart preparations.

Selectivity of alinidine for SA nodal automaticity vs. other cardiac activities was investigated using isolated, blood-perfused SA node, AV node and papillary muscle preparations of the dog. The drug was administered intra-arterially. In SA node preparations alinidine (1 microgram-1 mg) produced a dose-dependent decrease of sinus rate down to about 74% of the basal value at 1 mg, but no atrial standstill. In AV node preparations alinidine, injected into the posterior septal artery (PSA) which supplies the AV node, prolonged AV conduction time up to about 124% of the basal value but only in large doses (30 micrograms-1 mg). In the same preparations, when injected into the anterior septal artery, which supplies structures from the His bundle down to the ventricular septum (the intraventricular conduction system), alinidine in large doses (300 micrograms-1 mg) also prolonged AV conduction time nearly to the same extent as when injected into the PSA. In both cases neither second- nor third-degree AV block occurred. In paced papillary muscle preparations alinidine reduced the force of contraction down to about 64% of the basal value but in large doses (100 micrograms-1 mg). In spontaneously beating papillary muscle preparations alinidine reduced the rate of ventricular automaticity down to about 78% of the basal value but in large doses (100 micrograms-1 mg). Alinidine (100 micrograms-1 mg) produced a transient increase in blood flow in these preparations but not in SA node preparations. The cardiac effects of alinidine were longer-lasting than its vascular effect and the reduction of sinus rate was particularly long-lasting. The order of selectivity of alinidine determined from the above results is as follows: SA nodal automaticity much greater than ventricular automaticity greater than intraventricular conduction divided by AV nodal conduction divided by cardiac muscle contraction divided by coronary blood flow. Such a cardiovascular profile of alinidine is different from that of AQ-A 39, another bradycardic agent, which is nearly equi-effective on both SA nodal and ventricular automaticity.

Animals↗
PubMed1984

Cardiovascular actions of the dihydropyridine calcium antagonist nimodipine in the dog.

When injected i.v. into anaesthetized, open-chest dogs, isopropyl (2-methoxyethyl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3, 5-pyridinedicarboxylate (nimodipine, Bay e 9736) (0.3-10 micrograms/kg) produced an increase in coronary sinus outflow and decreases in mean arterial blood pressure, coronary resistance, arterio-venous oxygen difference and heart rate in a dose-dependent manner, but virtually no change in myocardial oxygen consumption. At 3 micrograms/kg i.v. of the drug coronary resistance fell nearly to half the pre-drug value, coronary sinus outflow nearly doubled and heart rate decreased by about 10 beats/min. Myocardial oxygen consumption was slightly reduced at 30 micrograms/kg i.v. and atrioventricular (AV) conduction time was slightly increased at 10 and 30 micrograms/kg i.v. of the drugs. When the coronary vascular and cardiac effects of nimodipine were assessed in isolated, blood-perfused dog heart preparations, i.e., sinoatrial node, AV node and papillary muscle preparations, by intra-arterial administration, the following was revealed. In nearly twice the dose doubling coronary arterial blood flow, nimodipine produced a 15% decrease in sinus rate and a 15% increase in AV conduction time. However, in reducing the force of contraction of the papillary muscle by half the pre-drug value was needed nearly 17 times the dose of nimodipine doubling coronary arterial blood flow. Suppression of AV conduction by large doses of nimodipine was evident only when it was injected into the artery supplying the AV node but not into the artery supplying the His-Purkinje-ventricular system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Analyses of the cardiac action of the bradycardic agent, AQ-A 39, by use of isolated, blood-perfused dog-heart preparations.

The cardiac and coronary vasodilator actions of AQ-A 39 were investigated in various isolated, blood-perfused dog-heart preparations. AQ-A 39 was injected i.a. In sinoatrial (SA) node preparations, AQ-A 39 (3 micrograms-3 mg) decreased sinus rate but rarely produced atrial standstill even in large doses (1-3 mg). In paced atrioventricular (AV) node preparations, AQ-A 39 injected into the posterior septal artery (which supplies the AV node) increased AV conduction time (i.e., AV nodal conduction time) in rather large doses (100 micrograms-1 mg), but produced neither second-nor third-degree AV block even with the largest dose examined (1 mg). In the same preparations, AQ-A 39 injected into the anterior septal artery (which supplies the His-Purkinje-ventricular system) prolonged AV conduction time (i.e., intraventricular conduction time) in rather large doses (0.3-1 mg). In paced papillary muscle preparations, AQ-A 39 reduced force of contraction only in large doses (1-3 mg). In spontaneously beating papillary muscle preparations, AQ-A 39 (10 micrograms-3 mg) decreased rate of automaticity and force of contraction only with large doses (1-3 mg). In all preparations, AQ-A 39 (30 micrograms-3 mg) increased blood flow. The order of effectiveness of AQ-A 39 on the above cardiovascular variables is as follows: ventricular automaticity not equal to SA nodal automaticity much greater than AV nodal conduction not equal to intraventricular conduction not equal to coronary blood flow not equal to ventricular muscle contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Relationship between relaxation and cyclic GMP formation caused by nicorandil in canine mesenteric artery.

In the isolated canine mesenteric artery relaxation caused by nicorandil [N-(2-hydroxyethyl)nicotinamide nitrate ester; SG-75] in the presence of noradrenaline was accompanied by a concomitant elevation of cGMP level, whilst the cAMP level was not changed by the drug. The relaxation and cGMP level after the administration of nicorandil showed a good correlation. In this respect nicorandil is very similar to nitrogen oxide-containing vasodilators.

Animals↗
PubMed1983

Effects of manganese ions and diltiazem on the spontaneous action potential of the canine atrio-ventricular node cell.

Effects of Mn2+ (10(-4) to 10(-3) M) and diltiazem (10(-7) to 10(-6) M) on the spontaneous action potential were studied in small preparations of the canine atrio-ventricular (A-V) node. Mn2+ and diltiazem decreased the maximum rate of rise (Vmax), amplitude of the action potential and rate of depolarization of the slow diastolic depolarization in a concentration-dependent manner. The spontaneous action potentials were depressed by the drugs, and were changed into abortive action potentials. Decrease in the rate of depolarization of the slow diastolic potential was much more prominent with Mn2+ than with diltiazem. These results indicate that the slow inward current may not play an important role in the initiation of the slow diastolic depolarization of the A-V node cell.

Action Potentials↗
PubMed1983

Improvement by trapidil of cardiac function of the dog heart-lung preparation depressed by pentobarbital.

The effect of trapidil on depressed cardiac function was investigated in 5 dog heart-lung preparations. Trapidil at a dose of 60 mg improved cardiac function which had been severely depressed by 70 +/- 32 (S.D.) mg of sodium pentobarbital. This dose of trapidil, however, produced no significant increase in heart rate. The results suggest that trapidil would be useful in the treatment of heart failure.

Animals↗
PubMed1983

Sustained coronary constriction and its antagonism by calcium-blocking agents in monkeys and baboons.

Experiments were performed on five Japanese monkeys and one anubis baboon anesthetized initially with ketamine hydrochloride and subsequently with sodium pentobarbital, and maintained on artificial respiration. The left anterior descending coronary artery (LAD) was cannulated and its vascular bed was perfused with arterial blood. Perfusion pressure was kept constant at a value slightly higher than the mean systemic arterial pressure. Blood flow through the LAD was measured by an electromagnetic flow meter. All drugs were administered into the LAD. Single injections of acetylcholine produced a biphasic change in blood flow; an initial decrease (vasoconstriction) followed by an increase (vasodilation). Infusion of acetylcholine produced a sustained decrease in blood flow in all the animals used except one Japanese monkey in which oscillatory changes in blood flow were induced. With infusions of acetylcholine, however, left ventricular pressure (LVP), and maximum rate of rise of LVP (LV dP/dt max), heart rate, and systemic arterial pressure remained unchanged. Single injections of diltiazem and nifedipine, calcium-blocking agents, and nitroglycerin produced a dose-related increase in blood flow. Diltiazem and nifedipine exerted no effects on other cardiohemodynamic variables, whereas nitroglycerin produced a decrease in systemic arterial pressure and an increase in heart rate. When blood flow through the LAD was reduced to nearly half of the basal value by infusion of acetylcholine, diltiazem and nifedipine produced an increase in blood flow as much as in control, whereas nitroglycerin produced less of an increase than in control.

Acetylcholine↗
PubMed1982

alpha-Adrenoceptors mediating the positive inotropic effect of phenylephrine in the right ventricular muscle of the monkey (Macaca fuscata).

The property of adrenoceptors mediating the positive inotropic effect (PIE) in the ventricular muscle of the Japanese monkey (Macaca fuscata) was investigated by the use of phenylephrine (PE) and adrenoceptor antagonists. The intrinsic activity (0.6) and the pD2-value (5.41) for PE were comparable to those in other mammalian species. The beta-adrenoceptor antagonist, pindolol (3 x 10(-8) mol/l) shifted only the upper part of the concentration-response curve (CRC) for PE to the right; the pD2-value for PE was not significantly affected by pindolol. On the other hand, phentolamine (10(-6) mol/l) shifted the lower part of the CRC for PE more than the upper part. In the presence of both pindolol and phentolamine the curve was shifted to the right in a parallel manner. The time required for twitch relaxation was negatively correlated to the degree of PIE of PE in the presence of phentolamine but not pindolol. These results indicate that both beta- and alpha-adrenoceptors mediate the positive inotropic action in the ventricular muscle of the Japanese monkey and that in contrast to the action via beta-adrenoceptors the action via alpha-adrenoceptors is not accompanied by the "relaxant effect".

Animals↗
PubMed1982

Further evidence for postganglionic actions of prostaglandin F2 alpha and histamine in the submandibular gland of the dog.

To test the possibility that prostaglandin F2 alpha and histamine might produce salivary and vasodilator responses by stimulation of preganglionic parasympathetic nerve fibers in the submandibular gland the responses to the two substances of chronically decentralized glands were compared with those of acutely decentralized ones in anesthetized dogs. No significant differences in responses to either prostaglandin F2 alpha or histamine were noted between chronically decentralized glands and acutely decentralized ones. Thus, it was concluded that prostaglandin F2 alpha and histamine only stimulate parasympathetic postganglionic neurons within the gland and neither of the responses is related to non-cholinergic ganglionic transmission.

Acetylcholine↗
PubMed1982

Effects of nicorandil and its congeners on musculature and vasculature of the dog trachea in situ.

In anesthetized dogs, the tracheal vascular bed in situ was perfused with arterial blood through the cannulated cranial thyroid arteries. The effects of nicorandil, a coronary vasodilator, and its congeners (SG-212, GS-209 and SG-103; in which the nitroxy group of nicorandil was substituted for other groups) on the tracheal musculature and vasculature were examined. All drugs were injected intra-arterially. Nicorandil (10-300 micrograms), SG-212 (100 micrograms-3 mg), SG-209 (100 micrograms-3 mg) and SG-103 (100 micrograms-3 mg) all produced a decrease in tracheal tone elevated by neostigmine (tracheal dilatation) and an increase in tracheal blood flow (tracheal vasodilatation). Relative potencies of these effects were in the descending order: nicorandil greater than SG-212 = SG-209 = SG=103 in producing tracheal vasodilatation. These results suggest that nicorandil would also be a potential bronchodilator and that the nitrate site in nicorandil plays a role in potentiating the pharmacological activity of congeners of nicorandil.

Animals↗