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N Taira

Publications and source records attributed to N Taira.

301 records · Page 17Linked to original sources
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Coronary vasodilator compared to cardiac effects of PY 108-068, a new dihydropyridine vasodilator, on isolated, blood-perfused dog-heart preparations.

We evaluated coronary vasodilator and cardiac effects of PY 108-068 on isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs. PY 108-068 was administered intra-arterially (i.a.). PY 108-068 increased (coronary) blood flow in all preparations. In SA node preparations, the drug produced a decrease in sinus rate and, in large doses, atrial standstill. In AV node preparations, the drug produced an increase in AV conduction time. Large doses caused second- or third-degree AV block, but only when injected into the artery supplying the AV node. The doses producing a 15% (nearly half maximum) decrease in sinus rate or a 15% (nearly half maximum) increase in AV conduction time were two to three times the doses that doubled coronary blood flow. In paced papillary muscle preparations, the drug produced a decrease in the force of contraction. However, the dose required to reduce the force of contraction of the papillary muscle by 50% was about 30 times the dose that doubled coronary blood flow. The drug was entirely ineffective on rate of ventricular automaticity. We conclude that PY 108-068 is not likely to produce reflex tachycardia when administered systemically in coronary vasodilator doses.

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PubMedDate not supplied

Separation of the coronary vasodilator from the cardiac effects of PN 200-110, a new dihydropyridine calcium antagonist, in the dog heart.

Coronary vasodilator and cardiac effects of PN 200-110 were compared by use of isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs. PN 200-110 was administered intraarterially. In all preparations PN 200-110 produced an increase in coronary blood flow. In SA node preparations, the drug produced a decrease in sinus rate and atrial standstill as well, but only in large doses. The dose that produced a 15% (nearly half-maximum) decrease in sinus rate was about three times the dose that doubled coronary blood flow. In AV node preparations, the drug produced an increase in AV conduction time and, in large doses, second- or third-degree AV block only when it was injected into the artery supplying the AV node. The dose that produced a 15% (nearly half-maximum) increase in AV conduction time was approximately 12 times the dose that doubled coronary blood flow. In paced papillary muscle preparations, the drug produced a decrease in the force of contraction. However, the dose that produced a 50% decrease in the force of contraction of the papillary muscle was approximately 14 times the dose that doubled coronary blood flow. These effects of PN 200-110 were of long duration. The drug was entirely ineffective in changing the rate of ventricular automaticity. The order of selectivity of PN 200-110 was as follows: coronary blood flow greater than SA nodal automaticity greater than AV nodal conduction greater than ventricular muscle contraction. This cardiovascular profile of PN 200-110 is slightly different from that of PY 108-068, a compound closely related to PN 200-110 in chemical structure.

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PubMedDate not supplied

The mechanism underlying the vasodilator action of bunitrolol: contribution of alpha 1-adrenoceptor blocking action.

The mechanism of the vasodilator action of bunitrolol was investigated in pentobarbital-anesthetized dogs. When injected intraarterially, bunitrolol increased blood flow through the femoral arterial bed more effectively than that through the vascular bed of the left anterior descending coronary artery (LAD). The former is rich in alpha-adrenoceptors and tonically controlled by the sympathetic nerves, whereas the latter is not. Intraarterial prazosin increased femoral flow but not LAD flow, whereas intraarterial nitrendipine increased equieffectively both femoral and LAD flows. In the saphenous arterial bed of dogs that also underwent spinal anesthesia and received atropine and nadolol, intravenous bunitrolol suppressed more effectively vasoconstrictor responses to saphenous nerve stimulation than those to intraarterial norepinephrine. These effects of bunitrolol were similar to those of prazosin and dissimilar to those of yohimbine. In similarly treated dogs, bunitrolol suppressed more effectively increases in mean systemic arterial pressure in response to methoxamine than those to B-HT 920. From these results, it was concluded that an alpha 1-adrenoceptor blocking action is mainly involved in the acute vasodilator effect of bunitrolol. This action may also contribute to the decrease in total peripheral resistance seen in hypertensive patients treated chronically with bunitrolol.

Anesthesia, Spinal↗
PubMedDate not supplied

Effects of quinidine on blood flow rate and developed tension in blood-perfused canine papillary muscle.

1. The effects of quinidine on blood flow rate and developed tension were studied in isolated, blood-perfused papillary muscle preparations of the dog. Drugs were injected into the anterior septal artery. 2. Quinidine caused a dose-related increase in blood flow rate; the mean dose producing a 100% increase in blood flow rate was about 0-3 mg. 3. Quinidine in doses of 0-01-0-1 mg produced a positive inotropic response. With 0-3--1 mg of quinidine the positive inotropic response was preceded by a transient negative inotropic response. With 3 mg there was a monophasic negative inotropic response, the developed tension being reduced by about 40% of control. 4. Propranolol had no statistically significant effects on the responses of the blood flow rate and developed tension caused by quinidine. 5. These results indicate that quinidine has an action on coronary vessels in lower doses than on the myocardium, and that in low doses it has a positive inotropic action rather than the well-known negative inotrophic action exerted with higher doses.

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Inhibition of excitation-contraction coupling in the ventricular myocardium of the dog by SKF 24260.

1. The effects of SKF 24260 on the coronary vasculature and on the electrical and mechanical activities of the ventricular myocardium were studied by the use of papillary muscle preparations of the dog. The preparation was cross-circulated from a donor dog through the anterior septal artery, and driven at a rate of 120 beats/min. Drugs were injected into the anterior septal artery. 2. SKF 24260, in doses of 0-01-100 mug, caused a dose-dependent increase in the rate of blood flow through the anterior septal artery; the mean dose producing a 100% increase in blood flow rate was about 0-7 mug. 3. SKF 24260 in doses of 0-01-0-03 mug produced a slight increase in developed tension of papillary muscles. With 0-1-0-3 mug of SKF 24260 the increase was preceded by a transient decrease, and with doses larger than 1 mug the drug caused a dose-dependent decrease. The mean dose producing a 50% decrease in developed tension was about 2-8 mug. 4. SKF 24260 failed to affect the amplitude and shape of bipolar electrograms even in doses of 39-100 mug which completely abolished the developed tension. 5. The decrease in the developed tension caused by SKF 24260 was overcome by exogenous calcium; the increase in the developed tension in response to exogenous calcium was antagonized by SKF 24260. 6. These results indicate that the dilator action of SKF 24260 on the coronary vasculature is more prominent than the negative inotropic action on the ventricular myocardium, and suggest that the negative inotropic action is probably due to antagonism of the role of calcium in excitation-contraction coupling.

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Positive inotropic action of glyceryl trinitrate as observed in the blood-perfused papillary muscle preparation of the dog heart.

1. The effects of glyceryl trinitrate on the coronary vasculature and on the contractility of the ventricular myocardium were investigated by the use of papillary muscle preparations of the dog, and that on the sino-atrial node activity by the use of sino-atrial node preparations of the dog. The papillary muscle preparation was cross-circulated through the anterior septal artery and the sino-atrial node preparation through the sinus node artery from a donor dog. The papillary muscles were driven at a rate of 120 beats/min. Drugs were injected close-arterially. 2. Glyceryl trinitrate, in doses of 0-03-100 microgram, produced dose-related increases in blood flow and developed tension. An increase in developed tension caused by 100 microgram of glyceryl trinitrate amounted to about 24% of the basal developed tension. Large doses of glyceryl trinitrate (100-300 microgram) produced a negative inotropic effect after a positive one in some preparations. 3. The positive inotropic effect of glyceryl trinitrate was not modified by propranolol, excluding a possible participation of an adrenergic mechanism. 4. Glyceryl trinitrate in large doses failed to modify the positive inotropic effect of calcium chloride. 5. Glyceryl trinitrate in a wide range of doses (0-03-100 microgram) had virtually no effect on sino-atrial node activity.

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PubMedDate not supplied

Assessment of the coronary vasodilator action of SK&F 24260 in the dog.

1. The effects of SK&F 24260 administered intravenously or intraduodenally on the coronary outflow, coronary arteriovenous oxygen difference (A-V O2), myocardial oxygen consumption (MVO2), systemic blood pressure, heart rate and atrioventricular (AV) conduction time were examined in open-chest dogs. 2. SK&F 24260 in doses of 0.3-10 microgram/kg, i.v., caused a dose-dependent increase in coronary sinus outflow, but the increase was smaller with 30 microgram/kg, i.v., than with 10 microgram/kg, i.v. 3. SK&F 24260 (0.3-30 microgram/kg, i.v.) decreased A-V O2 and MVO2 in a dose-dependent manner. 4. SK&F 24260 (0.3-30 microgram/kg, i.v.) decreased systemic blood pressure and heart rate, and increased AV conduction time. 5. Intraduodenal administration of SK&F 24260 (1 mg/kg) produced almost the same effects on coronary sinus outflow, A-V O2, MVO2, systemic blood pressure, heart rate and AV conduction time as did the intravenous administration of the compound (10 microgram/kg). 6. The property of SK&F 24260 to increase the coronary blood flow and to moderately decrease MVO2, systemic blood pressure and heart rate indicates that this agent is a potential antianginal drug.

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PubMedDate not supplied

Pharmacological profile of a new coronary vasodilator drug, 2-nicotinamidoethyl nitrate (SG-75).

1. In anaesthetized, open-chest dogs, 2-nicotinamidoethyl nitrate (SG-75) administered intravenously (0.3-1 mg/kg) or intraduodenally (3 mg/kg) produced decrease in systemic blood pressure, coronary resistance, heart rate and an increase in coronary sinus outflow, but virtually no change in myocardial oxygen consumption and atrioventricular conduction. The effects of SG-75 administered intraduodenally emerged within a few minutes after dosing and lasted over about 1 h. 2. In isolated, blood-perfused sino-atrial node preparations of the dog SG-75 administered into the sinus node artery decreased slightly sinus rate at the dose which doubled blood flow through the artery. 3. In isolated, blood-perfused atrioventricular node preparations of the dog SG-75 administered into the atrioventricular node artery did not impair atrioventricular conduction even in doses which increased blood flow through the artery to more than twice the basal level. 4. In isolated, blood-perfused papillary muscle preparations of the dog SG-75 administered into the anterior septal artery scarely affected force of contraction of the papillary muscle at the dose which doubled blood flow through the artery, although in further large doses it produced a transient decrease in the force of contraction. In extremely large doses it produced ventricular fibrillation. 5. In anaesthetized, open-chest dogs in which cardiac input was kept constant SG-75 (0.01-1 mg/kg) administered into the ascending aorta increased venous return without changing systemic output. 6. 2-Nicotinamidoethyl alcohol, a denitrated compound of SG-75, had no vasodilator action in doses comparable to those of the parent compound. 7. These results indicate SG-75 to be a potential antianginal drug having no cardiodepressant actions but having properties uncharacteristic of the nitrates.

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PubMedDate not supplied

Mechanisms underlying the cardiovascular action of a new dihydropyridine vasodilator YC-93.

1. The mechanisms underlying the cardiovascular action of YC-93, a new dihydropyridine vasodilator with cyclic AMP phosphodiesterase inhibitory activity, was investigated by comparing its effects with those of papaverine in various isolated, blood-perfused heart preparations of the dog. 2. In all preparations YC-93 injected into the nutrient arteries produced a dose-dependent increase in blood flow, and in this respect YC-93 was about twenty times more potent than papaverine on a weight basis. 3. In sinoatrial node preparations YC-93 injected into the sinus node artery decreased sinus rate in a dose-dependent manner, and in large doses produced atrial standstill. 4. In atrioventricular (a.v.) node preparations YC-93 injected into the a.v. node artery increased a.v. conduction time in a dose-dependent manner, and in large doses produced a second or third degree block of a.v. conduction. However YC-93 injected into the anterior septal artery scarcely affected a.v. conduction. 5. In spontaneously contracting papillary muscle preparations YC-93 injected into the anterior septal artery failed to affect ventricular automaticity in doses which markedly decreased developed tension of papillary muscles. 6. In papillary muscle preparations driven at a fixed rate YC-93 injected into the anterior septal artery produced a dose-dependent decrease in developed tension of papillary muscles. 7. Unlike YC-93, papaverine decreased a.v. conduction time in a.v. node preparations and increased developed tension of papillary muscle preparations. 8. The cardiac effects of YC-93 elucidated in the present experiments are characteristic of calcium-antagonistic vasodilators. The action of YC-93 as an inhibitor of cyclic AMP phosphodiesterase does not appear to play a role in its cardiac action.

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Vitamin D3 analogue KH1060 combined with TPA synergistically induces mature macrophages in human myeloblastic leukemia ML-1 cells.

A human myeloblastic leukemia cell line, ML-1, was induced to differentiate along the monocytic lineage following exposure to a 1,25-dihydroxyvitamin D3 analogue, 20-epi-22-oxa-24a,26a,27a-tri-homo-1,25-dihydroxyvitam in D3 (KH1060) or 12-O-tetradecanoylphorbol-13-acetate (TPA). The combination of KH1060 and TPA synergistically induced differentiation of ML-1 cells into mature macrophages with multinuclei. Maturation was also observed in other differentiation characteristics such as phagocytic activity, a-naphthyl acetate esterase activity, and expression of surface antigen CD14. Differentiated ML-1 cells showed attenuation of telomerase activity and cessation of proliferating activity based on evaluation of the expression of genes related to cell growth potential. Remarkable synergism was observed in TNF production. Treatment with TPA prior to KH1060 resulted in only slight production of TNF; however, treatment with KH1060 preceding TPA induced a substantial amount of TNF.

Calcitriol↗
PubMedDate not supplied

K+ channel-opening action and KRN2391-induced reduction of Ca2+ sensitivity of arterial smooth muscle.

To clarify the vasodilating mechanism of KRN2391, a novel vasodilator having a combined nitrate-like and K+ channel-opening action, we investigated its effects on membrane potentials, intracellular Ca2+ concentrations ([Ca2+]i) and force of contraction in canine coronary artery. KRN2391 hyperpolarized the membrane of arterial smooth muscle cells in 5 and 30 mM KCl-physiological salt solutions. KRN2391 reduced the increases in [Ca2+]i and force of contraction induced by 30 mM KCl-physiological salt solution and the effect on [Ca2+]i was almost abolished by 10(-5) M glibenclamide, although the effect on force of contraction was only partially inhibited. The [Ca2+]i-force curves in the presence of KRN2391 or the selective K+ channel openers Ki4032 and cromakalim were shifted to the right, as compared to the control curve determined by varying the extracellular Ca2+ concentration ([Ca2+]o). This finding indicates that these substances reduce the Ca2+ sensitivity of contractile elements (Ca2+ desensitization). The Ca(2+)-desensitizing action of KRN2391 was partly antagonized by 10(-5) M glibenclamide. There was no interaction between nitroglycerin and cromakalim or Ki4032. These results suggest that, in addition to the nitrate-like action, the opening of the K+ channel by KRN2391 reduces not only [Ca2+]i but also the Ca2+ sensitivity of contractile elements, resulting in vasodilatation.

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