Biomedical subjects

N Taira

Publications and source records attributed to N Taira.

At least 55 records · Page 3Linked to original sources

PubMed1994

Vasodilator mechanisms of action of amrinone do not involve the opening of either ATP-sensitive or Ca(2+)-activated K+ channels.

Amrinone is more coronary vasodilatory than positive inotropic compared with other newer phosphodiesterase inhibitors. In order to explore possible involvements of ATP-sensitive K+ (KATP) and large-conductance Ca(2+)-activated K+ (KCa) channels in the vasodilator effect of amrinone, we investigated whether amrinone-induced vasodilation would be antagonized by glibenclamide, a blocker of KATP channels, or by charybdotoxin or tetraethylammonium, blockers of KCa channels. In isolated, blood-perfused canine papillary muscle preparations, the amrinone-induced increase in blood flow was not affected by glibenclamide given to support dogs. In canine large coronary arteries contracted with high (25 mM) KCl, amrinone-induced relaxation was not affected by glibenclamide, charybdotoxin and tetraethylammonium. These results suggest that the vasodilator mechanisms of amrinone do not involve the opening of either KATP or KCa channels.

Adenosine Triphosphate↗

PubMed1993

Opening of ATP-sensitive K+ channels responsible for adenosine A2 receptor-mediated vasodepression does not involve a pertussis toxin-sensitive G protein.

Whether the opening of ATP-sensitive K+ channels responsible for adenosine A2 receptor-mediated vasodepression involves a pertussis toxin (PTX)-sensitive G protein was investigated in pithed rats. Adenosine and levcromakalim were used as reference substances. The blood pressure of pithed rats was kept elevated with an i.v. infusion of methoxamine. 2-(1-Octynyl)-adenosine (YT-146; 0.1-10 micrograms/kg i.v.), a selective adenosine A2 receptor agonist, produced a dose-dependent and long-lasting decrease in mean blood pressure (MBP) scarcely affecting heart rate (HR). Levcromakalim (0.3-10 micrograms/kg per min i.v. for 20 min) produced a dose-dependent and slowly developing decrease in MBP. The vasodepressor effects of YT-146 and levcromakalim were antagonized by glibenclamide (20 mg/kg i.v.), a blocker of ATP-sensitive K+ channels; the ED50 values for YT-146 and levcromakalim both increased about 2.5-fold. In rats pretreated with PTX (10 micrograms/kg i.v.), in which vagally induced bradycardia was nearly abolished, the vasodepressor effects of YT-146 and levcromakalim were slightly enhanced. Adenosine (0.3-10 mg/kg per min i.v. for 1 min) produced a dose-dependent and long-lasting decrease in MBP accompanied by a transient decrease in HR. The vasodepressor effect of adenosine was antagonized by glibenclamide; the ED50 value for adenosine increased about 3.2-fold, but not after PTX pretreatment. In contrast, the transient bradycardia was antagonized by PTX pretreatment but not by glibenclamide. These results suggest that the opening of ATP-sensitive K+ channels in vascular smooth muscle following stimulation of adenosine A2 receptors by YT-146 and adenosine does not involve a PTX-sensitive G protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1993

Involvement of ATP-sensitive K+ channels in the sustained coronary vasodilator response to adenosine in dogs.

Coronary vasodilator mechanisms of adenosine were investigated in isolated canine papillary muscle preparations cross-circulated through the anterior septal artery with support dogs. Infusions of adenosine (1-3000 nmol/min) for 3 min into this artery caused a transient increase (the initial phase) in blood flow followed by a sustained increase (the sustained phase), and single-bolus intra-arterial injections of adenosine (0.3-1000 nmol) produced only a transient increase in blood flow. The force of contraction of the papillary muscle was virtually unaffected. The increase in blood flow in the sustained phase was antagonized by glibenclamide (6 mumol/kg i.v.), a blocker of ATP-sensitive K+ channels, administered to support dogs whereas increases in both phases were antagonized by 8-phenyltheophylline (12 mumol/kg i.v.), a non-selective adenosine receptor antagonist, administered in a similar way. The transient increase in blood flow caused by single-bolus injections of adenosine was reduced in duration rather than in peak value by glibenclamide. Thus, it appears that opening of ATP-sensitive K+ channels gradually becomes involved in the vasodilator mechanisms for adenosine A2 receptor-mediated, sustained vasodilation.

Adenosine↗

PubMed1993

BRL 38227 (levcromakalim)-induced hyperpolarization reduces the sensitivity to Ca2+ of contractile elements in canine coronary artery.

Potassium (K+) channel openers decrease intracellular free Ca2+ concentrations ([Ca2+]i by hyperpolarizing the membrane and deactivating the Ca(2+)-channels. To examine whether the hyperpolarization produced by K(+)-channel openers has other effects on the mechanical activity of vascular smooth muscle, we investigated the effects of levcromakalim (BRL 38227) on membrane potential, [Ca2+]i, as measured with fura-2, and force of contraction induced by 30 mmol/l KCl-physiological salt solution (PSS), in canine coronary arteries. BRL 38227 hyperpolarized the membrane and reduced increases in [Ca2+]i and in contractile force induced by 30 mmol/l KCl-PSS. The [Ca2+]i-contractile force curve, determined in the presence of BRL 38227, was located to the right of the control curve determined by decreasing extracellular Ca2+ concentrations ([Ca2+]o) in 30 mmol/l KCl-PSS. The [Ca2+]i-contractile force curve, determined by decreasing extracellular K+ concentrations ([K+]o), was also located to the right of that determined by decreasing [Ca2+]o in 30 mmol/l KCl-PSS. The effect of BRL 38227, a reduction in the Ca(2+)-sensitivity of contractile elements, was antagonized by the ATP-sensitive K(+)-channel blocker, glibenclamide (10(-6) or 10(-5) mol/l). These results suggest that the membrane hyperpolarization induced by BRL 38227, or the repolarization caused by reducing [K+]o, decreases the Ca(2+)-sensitivity of contractile elements of vascular smooth muscle.

Animals↗

PubMed1993

Nicorandil as a nitrate, and cromakalim as a potassium channel opener, dilate isolated porcine large coronary arteries in an agonist-nonselective manner.

Nicorandil is an antianginal vasodilator having a hybrid property between nitrates and potassium channel openers, and cromakalim is a relatively specific potassium channel opener. We investigated whether or not the vasorelaxant actions of the two drugs would be selective for certain vasoconstrictor agonists (simply agonists hereafter), and the underlying mechanisms in isolated porcine large coronary arteries. Both nicorandil and cromakalim produced a complete relaxation in the arteries precontracted with seven agonists, i.e., Bay-K-8644, endothelin, histamine, 5-hydroxytryptamine (5-HT), phenylephrine, PGF2 alpha, and U 46619. The EC50 values (-log M) of nicorandil and cromakalim were 5.20-5.44 and 6.43-6.87, respectively, toward the seven agonists, indicating that the vasorelaxant actions of the two drugs were agonist nonselective. In the arteries precontracted with Bay-K-8644, endothelin, 5-HT, and U 46619, the vasorelaxant action of cromakalim was antagonized by glibenclamide, an antagonist of potassium channel openers, and Schild analysis of these antagonisms yielded pA2 values of 7.10-7.41 for glibenclamide. The vasorelaxant actions of nicorandil in the arteries precontracted with the four agonists each were not antagonized by glibenclamide. Instead, the vasorelaxant action of nicorandil was antagonized by methylene blue (10 microM), an inhibitor of guanylate cyclase, and slightly potentiated by M&B 22,948 (10 microM), an inhibitor of cyclic-GMP phosphodiesterase, in the arteries precontracted with U 46619. These results indicate that the vasorelaxant actions of nicorandil and cromakalim in the porcine large coronary artery are agonist nonselective and that nicorandil exerts such an action entirely as a nitrate, whereas cromakalim does so entirely as a potassium channel opener.

Animals↗

PubMed1993

Sudden death of calves by experimental infection with Strongyloides papillosus. IV. Electrocardiographic and pneumographic observations at critical moments of the disease.

Electrocardiographic and pneumographic observations at critical moments were carried out on five calves that died suddenly following experimental infections with Strongyloides papillosus. Time which elapsed during these critical moments was calculated from the time of observation of ventricular flutter (VF) to the appearance of accelerated respiration and cessation of respiration. The beginning of accelerated respiration ranged from -19 to 41 s after VF. Time (minutes:seconds) of cessation of respiration ranged from 2:10 to 3:50 after VF. The results of the experiment suggested sudden cardiac death as the cause of death in calves following infection with Strongyloides papillosus.

Animals↗

PubMed1993

Sudden death of calves by experimental infection with Strongyloides papillosus. III. Hematological, biochemical and histological examinations.

Nine calves infected percutaneously with graded doses of Strongyloides papillosus (SPL) were examined for hematological, biochemical and histological changes during the infection. Six of the calves infected with the highest larval doses died suddenly and the three calves given lower doses survived. No changes were observed in blood cell counts except for a transient eosinophilia. Parameters of the blood coagulation system and blood gas remained normal. A decrease in blood glucose was observed in four of the calves that died after the prepatent period of the parasite. However, endotoxic shock could be ruled out as a cause of death because of normal platelet counts, no intravascular coagulation and low levels of serum endotoxin. A transient increase of creatine kinase was observed in three of the calves that died; however, myocardial infarction or myocarditis were not observed. No lesions were observed except for minor inflammatory changes in the lungs and slight cellular infiltrations in the heart. In the absence of any consistent hematological, biochemical or histological changes in the calves that died, the present study failed to demonstrate mechanisms underlying sudden death due to SPL infection.

Animals↗

PubMed1993

ICI 147,798 causes insurmountable antagonism against T-0509, a selective beta 1-adrenoceptor agonist, but surmountable antagonism against isoproterenol.

In canine right ventricular muscle, the influence of ICI 147,798, a slowly dissociable beta 1-adrenoceptor antagonist, on the positive inotropic effect and cyclic AMP production of T-0509, a selective beta 1-agonist, and isoproterenol, a nonselective beta-agonist, were examined to elucidate the properties of the high- and low-affinity states or subtypes of beta 1-adrenoceptor. ICI 147,798 (1 x 10(-8) - 1 x 10(-5) M) produced biphasic concentration-response curves for the positive inotropic effect of T-0509 that were due to its insurmountable antagonism against the lower concentrations of T-0509. The maximum of the biphasic curves were almost the same as Camax. Analysis of hemiequilibrium antagonism by ICI 147,798 against T-0509 showed the dissociation constant (pKB) of ICI 147,798 to be approximately 8. On the other hand, ICI 147,798 produced a parallel rightward shift of the curves of isoproterenol. Schild analysis showed pA2 to be 7.98 +/- 0.04, suggesting competitive antagonism. The concentration-response curve for the increase in cyclic AMP elicited by T-0509 in the presence of 1 x 10(-6) M ICI 147,798 was also biphasic, but slightly depressed as compared with that of control, whereas that elicited by isoproterenol was shifted to the right. The positive inotropy and increase in cyclic AMP produced by T-0509 and isoproterenol in the presence of ICI 147,798 may be mediated by the low-affinity state of beta 1-adrenoceptor, which mechanism may be different from that producing the positive inotropy through the high-affinity state of beta 1-adrenoceptor.

Adrenergic alpha-Agonists↗

PubMed1993

Cardiovascular profile of Ro 40-5967, a new nondihydropyridine calcium antagonist, delineated in isolated, blood-perfused dog hearts.

Coronary and cardiac effects of Ro 40-5967 were compared in isolated, blood-perfused dog heart preparations. Intraarterial Ro 40-5967 increased blood flow in all preparations. In sinoatrial preparations, Ro 40-5967 decreased sinus rate and produced atrial stand-still when administered at high doses. In paced atrioventricular (AV) node preparations, Ro 40-5967 injected into the posterior septal artery (which perfuses the AV node) increased AV conduction time and at high doses produced second- or third-degree AV block. In the same preparations, Ro 40-5967 had little effect on AV conduction time, even at higher doses, when injected into the anterior septal artery (which perfuses the His-Purkinje ventricular system). In paced papillary muscle preparations, Ro 40-5967 reduced the force of contraction only at high doses. In spontaneously beating papillary muscle preparations, Ro 40-5967 decreased the force of contraction only at high doses and had no effect on the rate of automaticity even at higher doses. The dose that doubled blood flow was about one-fifth of the dose that produced a 15% decrease in sinus rate and also one-fifth of the dose that produced a 15% increase in AV conduction time. The dose that reduced the force of contraction by half was > 10 times the dose that doubled blood flow. The results indicate that the cardiovascular profile of Ro 40-5967 differs from those of verapamil and diltiazem but instead resembles that of dihydropyridine derivatives, which are classified as vasoselective calcium antagonists.

Animals↗

PubMed1993

Absence of effects of class III antiarrhythmic agents on cloned cardiac K channels.

We investigated the effects of class III antiarrhythmic agents, d-sotalol, E-4031 and MS-551, on the currents of two cloned K channels, Kv1.2 (IKv1.2) and Kv1.4(IKv1.4), by using the Xenopus oocyte expression system. Both IKv1.2 and IKv1.4 were sensitive to 4-aminopyridine and quinidine, but insensitive to tetraethylammonium, d-sotalol, E-4031 and MS-551. The results suggest that some types of structural proteins may be necessary for class III agents to inhibit the cardiac cloned K channels.

4-Aminopyridine↗

PubMed1993

Improvement of cardiac performance by pimobendan, a new cardiotonic drug, in the experimental failing dog heart.

The cardiotonic effect of pimobendan was studied in 6 dog heart-lung preparations in which cardiac function had been severely depressed by pentobarbital. Pimobendan in doses of 1-10 mg improved cardiac function in a dose-dependent manner and at 10 mg improved it beyond the control. These doses of pimobendan, however, produced neither a significant increase in heart rate nor arrhythmias. The results indicate that the drug may be of use in the treatment of heart failure.

Animals↗

PubMed1993

Calcitonin gene-related peptide relaxes porcine coronary arteries via cyclic AMP-dependent mechanisms, but not activation of ATP-sensitive potassium channels.

We investigated the relaxant mechanisms of calcitonin gene-related peptide (CGRP) in endothelium-denuded porcine coronary arteries. Intracellular free calcium concentration ([Ca++]i) was measured simultaneously with force by the fura-2 microfluorimetric method. CGRP (10(-9) to 10(-7) M) or isoproterenol (10(-8) to 10(-5) M) produced a concentration-dependent relaxation of arterial rings precontracted with 30 mM KCl with only a slight decrease in [Ca++]i. In contrast, cromakalim (3 x 10(-7) to 3 x 10(-5) M), an ATP-sensitive potassium channel opener, reduced [Ca++]i and force in a parallel manner. When the arteries were precontracted with 90 mM KCl, the relaxant effects of CGRP and isoproterenol were attenuated, whereas that of cromakalim was abolished. In arteries precontracted with 90 mM KCl, reduction of extracellular calcium concentrations from 2.5 to 0.1 mM recovered the relaxant effects of CGRP and isoproterenol, but not that of cromakalim. All three relaxants reduced both [Ca++]i and force in arteries precontracted with endothelin-1 (10(-8) M). Glibenclamide (10(-5) M) inhibited the decrease in [Ca++]i and the relaxation caused by cromakalim, but had virtually no effect on those produced by CGRP or isoproterenol. In arteries precontracted with 30 mM KCl and relaxed maximally by isoproterenol (10(-5) M), CGRP (10(-7) M) failed to produce any relaxant effect, whereas cromakalim (10(-5) M) reduced [Ca++]i and force further. The inhibitor of phosphodiesterase, 3-isobutyl-1-methylxanthine, potentiated the decreases in [Ca++]i and relaxations caused by CGRP and isoproterenol, but not those by cromakalim.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗

PubMed1993

Long-lasting parasitism of Strongyloides venezuelensis in Mongolian gerbils (Meriones unguiculatus).

Mongolian gerbils (Meriones unguiculatus) were infected with 100, 1,000 and 10,000 Strongyloides venezuelensis infective larvae (L3) to determine the duration of fecal egg output. Eggs per gram of feces (EPG) were counted chronologically, and adult worms in the small intestine were recovered on 100 days after infection. Changes of EPG in Mongolian gerbils infected with 10,000 L3 also were observed for 450 days. EPG was stable for each dose after the peak value noted 9 or 10 days after the infection. The EPG and number of worms recovered were dependent on the dose. The high EPG value continued for 450 days. These results demonstrate that Mongolian gerbils allowed a long-lasting parasitism of S. venezuelensis. Strongyloides venezuelensis-Mongolian gerbil systems may be useful for parasitological study of S. venezuelensis.

Animals↗

PubMed1992

Modulation of transient type K channel cloned from rat heart.

We have cloned a transient type K channel from rat heart (RH10) and coexpressed a metabotropic glutamate receptor (mGluR5) to study the functional modulation of RH10 coupled to the phosphatidylinositol (PI) hydrolysis. Stimulation of mGluR5 suppressed peak amplitude of RH10 current and affected voltage dependence of activation and inactivation of the channel.

Animals↗

PubMed1992

Activation of phospholipase C by the agonist U46619 is inhibited by cromakalim-induced hyperpolarization in porcine coronary artery.

We measured inositol 1,4,5-trisphosphate (IP3) production, intracellular calcium concentration ([Ca2+]i) and force of contraction induced by a thromboxane A2 analogue U46619 in porcine coronary artery to elucidate the relaxant effect of a K+ channel opener cromakalim. Cromakalim (10 microM) significantly inhibited the production of IP3, Ca2+ release from intracellular stores and contraction induced by 300 nM U46619. The inhibitory effect of cromakalim on IP3 was blocked by a K+ channel blocker tetrabutylammonium (TBA, 3 mM) and counteracted by 20 mM KCl-induced depolarization. These results suggest that the hyperpolarization of the plasma membrane by cromakalim inhibits the activation of phospholipase via the stimulation of the thromboxane A2 receptor to result in vasodilation.

Animals↗

PubMed1992

E4080 has a dual action, as a K+ channel opener and a Ca2+ channel blocker, in canine coronary artery smooth muscle.

To clarify the vasodilating mechanism of action of E4080, which possesses vasodilating and bradycardic effects, we investigated its effects on intracellular Ca2+ concentrations ([Ca2+]i), as measured with fura-2, and force of contraction in canine coronary artery. E4080 reduced the increase in [Ca2+]i and force of contraction induced by 30 and 90 mM KCl physiological salt solution (PSS) in a concentration-dependent manner. The effects of E4080 in 30 mM KCl-PSS were inhibited by 10(-5) M glibenclamide. In 30 mM KCl-PSS, the slope of the [Ca2+]i-force relationship in the presence of E4080 was steeper than that of control, suggesting that E4080 decreased the sensitivity of contractile elements to Ca2+, as an effect which was also inhibited by glibenclamide. However, the [Ca2+]i-force curve was not changed by E4080 in 90 mM KCl-PSS. These results suggest that E4080 is a vasodilator in canine coronary artery, having K+ channel opening and Ca2+ channel blocking actions. The membrane hyperpolarization induced by E4080 may reduce the sensitivity of contractile elements to Ca2+.

Analysis of Variance↗

PubMed1992

Cloning and modulation by endothelin-1 of rat cardiac K channel.

We have cloned a delayed rectifier type K channel from rat heart (RH1). RH1 was identical to the rat brain K channel BK2 and differed from recently cloned rat cardiac K channel RAK by one amino acid residue. Endothelin receptors(ETRs)-mediated modulation of RH1 current (IRH1) was studied using Xenopus oocyte expression system. Activation of two different subtypes of ETRs by endothelin-1 equally suppressed the amplitude of IRH1. Stimulation of phosphatidylinositol turnover will probably be responsible for the suppression.

Animals↗

PubMed1992

Vasodepressor mechanisms of 2-(1-octynyl)-adenosine (YT-146), a selective adenosine A2 receptor agonist, involve the opening of glibenclamide-sensitive K+ channels.

The vasodepressor mechanism of 2-(1-octynyl)-adenosine (YT-146), a selective adenosine A2 receptor agonist, was compared with that of adenosine in spinally anaesthetized dogs whose blood pressure was kept elevated with i.v. infusion of noradrenaline. Cumulative i.v. administration of YT-146 (1-1000 nmol/kg) caused a slowly developing and long-lasting decrease in mean blood pressure (MBP) and a small decrease in heart rate (HR) at high doses, whereas single i.v. administration of adenosine caused short-lived decreases in MBP and HR. In dogs given glibenclamide (6 mumol/kg i.v.) or theophylline (30 mumol/kg i.v.) dose-response curves for decrease in MBP due to YT-146 underwent parallel rightward shifts. The ED50 values for YT-146 were increased about 5.5-fold with glibenclamide and about 11.9-fold with theophylline. However, no further rightward shifts of the curves were obtainable in dogs given glibenclamide plus theophylline; the increase in ED50 values for YT-146 was about 6.8-fold, being close to the increase obtained with theophylline alone. The ED50 values for adenosine to lower MBP increased about 1.6-fold with theophylline but not with glibenclamide. Glibenclamide and theophylline failed to antagonize the negative chronotropic effects of both drugs. These results suggest that the vasodepressor effect of YT-146 involves two mechanisms following stimulation of adenosine A2 receptors; one is probably a cyclic AMP-dependent mechanism and the other is the opening of glibenclamide-sensitive K+ channels.

Adenosine↗