Search PubMed⌕ Search

Biomedical subjects

M Endoh

Publications and source records attributed to M Endoh.

At least 487 records · Page 27Linked to original sources
PubMed1976

Effects of prostaglandin E1 on the positive inotropic actions of noradrenaline, nerve stimulation and calcium in the isolated blood-perfused papillary muscle of the dog.

The effects of PGE1 on the dog heart were studied using the blood-perfused sinus node and papillary muscle preparations isolated separately from the same animal. PGE1 administered into the papillary muscle artery as bolus injections in doses of 1-1000 ng caused a dose-dependent increase of the developed tension and dT/dt of the papillary muscle. The effect was not inhibited by the beta-adrenoceptor blocking agent pindolol. PGE1 injected into the sinus node artery in doses of 3-300 ng did not change the rate of contraction of the sinus node preparation. PGE1 in the blood concentrations of 4.4 X 10(-9) to 1.7 X 10(-7) M enhanced the positive inotropic responses to noradrenalin and field stimulation as well as to calcium. The influence of PGE1 on the positive inotropic effect of perivascular nerve stimulation was not consistent: the action of perivascular nerve stimulation was enhanced by PGE1 in the majority of preparations but was reduced in one third of preparations. PGE1 in the same blood concentrations as used in the papillary muscle significantly depressed the positive chronotropic responses to noradrenaline and dopamine. The present results indicate that PGE1 induces multiple actions on the dog heart. Its predominant effect on the ventricular myocardium appears to be enhancement of the adrenergic stimuli probably via the facilitation of calcium movement through the myocardial cell membrane. In addition, PGE1 may decrease the sensitivity of beta-adrenoceptors to adrenergic stimuli in the sinus node.

Animals↗
PubMed1976

alpha-Adrenoceptors mediating positive inotropic effects on the ventricular myocardium: some aspects of structure-activity relationship of sympathomimetic amines.

Experiments were carried out on the isolated papillary muscle of the rabbit in order to further characterize the alpha-adrenoceptors mediating the positive inotropic effect. For this purpose dose-response relations of seven sympathomimetic amines were compared under the influence of alpha- and/or beta-adrenolytic drugs. Phentolamine (10(-6) M) shifted the lower part of the dose-response curves for norfenephrine, synephrine and epinine as for phenylephrine and adrenaline to the right, while prindolol (10(-8) M) affected only the upper part of the curves. In the presence of both alpha- and beta-adrenoceptor blocking agents the entire dose-response curves for sympathomimetic amines were shifted in a parallel manner. Noradrenaline affected preferentially beta-adrenoceptors, whereas its effect on alpha-adrenoceptors was so weak that it could be detected only when the neuronal and extraneuronal uptake mechanism of amines were blocked by cocaine (3 X 10(-5) M) and corticosterone (4 X 10(-5) M), respectively. The effect of dopamine was not affected either by phentolamine or by prindolol, but was antagonized by the simultaneous application of both alpha- and beta-adrenoceptor blocking agents. From the present results, it appears that the following relationships are present between the structure of amines and the alpha-adrenoceptor stimulating activity in the heart: (1) N-methylation increases the potency: (2) Absence of the hydroxyl group either in 3 or in 4 position decreases the intrinsic and beta-adrenoceptor stimulating activities, but increases the alpha-adrenoceptor stimulating activity.

Adrenergic alpha-Agonists↗
PubMed1975

Frequency-dependence of the positive inotropic effect of methoxamine and naphazoline mediated by alpha-Adrenoceptors in the isolated rabbit papillary muscle.

Under the conditions of different stimulation frequencies the inotropic effects of the alpha-adrenoceptor stimulationg agents, methoxamine, naphazoling and oxymetazoline were studied on the isolated rabbit papillary muscle. 1. On the papillary muscle stimulated at 0.5 Hz methoxamine in concentrations from 10(-5)M caused a significant and dose-dependent positive inotropic effect. At 10(-3)M methoxamine decreased the developed tension. With increasing frequency of stimulation (0.5--1--1.5Hz), the positive inotropic effect became smaller, while the negative inotropic one was more pronounced. The time course of the disappearance of the negative inotropic effect of methoxamine by washout differed from that of the positive inotropic effect: the negative component disappeared within 30 min, whereas the positive one lasted for about 100 min. The positive inotropic effect of noradrenaline (10(-6)M), in contrast ot that of methoxamine, was not influenced by the frequency under the same conditions of stimulation. Also naphazoline (10(-5)M) caused a significant positive inotropic effect on the papillary muscle stimulated at 0.5 Hz, while oxymetazoline induced exclusively a negative inotropic effect. 2. The positive inotropic effect of metoxamine (10(-4)M) as well as of naphazoline (10(-5)M) evoked at a frequency of 0.5 Hz was abolished by phentolamine (10(-6)M). Methoxamine (10(-4)M) induced a significant negative inotropic effect in the presence of phentolamine. Phentolamine antagonized the positive inotropic effect of methoxamine in a non-competitive manner: the pD2-value was 7.76. 3. In the presence of methoxamine (10(-4)M) the developed tension in the lower range (0.05--1 Hz) of the frequency-force relationship was enhanced, while that in the higher range (greater that 1.5 Hz) was decreased. The enhancement was abolished by phentolamine (10(-6)M). 4. Papaverine (2x10(-5)M) did not affect the positive inotropic effect of methoxamine. 5. The present results show that methoxamine and naphazoline induced a positive inotropic effect via alpha-adrenoceptor in the ventricular myocardium of the rabbit. These effects were caused only at low, but not at high frequencies of stimulation.

Animals↗
PubMed1975

Effects of papaverine on isolated rabbit papillary muscle.

The effect of papaverine on the positive inotropic response to isopreqaline and to calcium was studied on the rabbit isolated papillary muscle; theophylline and the calcium antagonistic D600 were used for comparison. The dose-response curve for isoprenaline was shifted to the left by papaverine (3 times 10- minus 6 to 3 times 10- minus 5 M), in a dose-dependent manner, while that for calcium was not affected by the same concentration. In this respect papaverine was about 30 times more potent than theophylline. In the presence of papaverine isoprenaline induced arrhythmic contractions of the papillary muscle: the incidence of arrhythmic contractions was positively correlated to the concentration of papaverine. Papaverine 10- minus 5 to 10- minus 4 M caused only a positive inotropic response whereas 3 times 10- minus 4 to 10- minus 3 M induced a biphasic response, i.e., after a positive inotropic effect followed a negative one. In the presence of 3 times 10- minus 4 M papaverine isoprenaline failed to cause a positive inotropic response but exclusively induced arrhythmic contractions. Calcium, on the other hand, readily antagonized the negative inotropic effect of papaverine (3 times 10- minus 4 M) and caused a contracture of the papillary muscle. The results indicate that papaverine (3 times 10- minus 6 to 10- minus 5 M) like theophylline (10- minus 4 to 10- minus 3 M) produces its effect by phosphodiesterase inhibition and thereby specifically potentiates the response through beta-adrenoceptor stimulation. In higher concentrations (3 times 10- minus 4 to 10- minus 3 M) it acts as a calcium antagonistic, like D600, and furthermore may interact with calcium moving through myocardial cell membranes to cause a contracture via a mechanism which it shares with theophylline.

Animals↗
PubMed1975

Effects of dopamine on sinus rate and ventricular contractile force of the dog heart in vitro and in vivo.

1 Experiments were carried out on dog isolated papillary muscle and sinus node preparations perfused with arterial blood from a donor dog. The chronotropic and inotropic effects of dopamine were analysed by using reserpine, desmethylimipramine (DMI), cocaine and phenoxybenzamine, and the relative chronotropic and inotropic effects defined, the results being compared with those for noradrenaline (NA). 2 The effects of dopamine administered intra-arterially into the isolated preparations were reduced by pretreatment of animals with reserpine both in the papillary muscle and sinus node. The chronotropic effects, however, were affected less by pretreatment with reserpine than were the inotropic effects. 3 Desmethylimipramine (DMI) reduced the inotropic and chronotropic effects of dopamine, and enhanced the effects of NA and nerve stimulation; the chronotropic effects of the amines were less affected than the inotropic effects. 4 Cocaine enhanced considerably the inotropic and chronotropic effects of NA, and decreased the inotropic but not the chronotropic effect of dopamine. 5 Phenoxybenzamine enhanced the inotropic effects of dopamine, NA and nerve stimulation, but did not affect the chronotropic effects of the amines. 6 When dopamine (1 to 300 mug/kg) was administered intravenously to the donor dog, it increased preferentially the contractile force of the ventricular myocardium with a comparatively small change of the sinus rate in the isolated preparations as well as in the heart in vivo. NA (0.1 to 10 mug/kg) caused effects similar to those of dopamine. The maximal inotropic responses to these catecholamines were reached with lower doses than the chronotropic ones. 7 It is concluded that both the positive inotropic and the positive chronotropic responses to dopamine are mediated partially by a direct and partially by an indirect stimulant effect on beta-adrenoceptors in the dog heart. The present results suggest that the difference in activity of dopamine and NA between the ventricular myocardium and the sinus node may be ascribed to the unequal innervation with adrenergic nerve fibres of the atrium and the ventricle (Furnival, Linden & Snow, 1971). The sinus node which is densely innervated by adrenergic nerve fibres may inactivate noradrenaline and dopamine more effectively than the ventricular myocardium through the uptake into the nerve and thereby be less sensitive to the exogenous catecholamines.

Animals↗
PubMed1975

Influence of temperature on the positive inotropic effects mediated by alpha-and-beta-adrenoceptors in the isolated rabbit papillary muscle.

On the isolated rabbit papillary muscle experiments were carried out to determine whether the positive inotropic effects mediated by alpha- and by beta- adrenoceptors are brought about by different mechanisms or not.--For this reason the influence of temperature and the effect of the calcium antagonist D600 on the responses to phenylephrine and to isoprenaline were compared. 1. The maximal inotropic effects of phenylephrine, isoprenaline and calcium were not affected by raising the temperature of the organ bath from 37 degrees to 42 degrees C, wheras the basal developed tension of the muscle was significantly decreased. 2. The dose-response curve for phenylephrine was markedly shifted to the right by raising the temperature (pD2=0.89), while that for isoprenaline was also shifted to the right, but to a lesser extent (pD2=0.23). 3. In the presence of 1.5 times 10-8 M pindolol the shift of the dose-response curve for phenylephrine induced by elevation of temperature was more prominent (pD2=1,91), whereas phentolamine (3 times 10-6 M) inhibited the temperature-induced shift. 4. The positive inotropic effect of phenylephrine--mediated by alpha-adrenoceptors under blockade of beta-adrenoceptors by 1.5 times 10-8 M pindolol--was markedly depressed by D600 (10-7 and 3 times 10-7 M): the dose-response curve was shifted to the right ant the maximal response was depressed. On the other hand, the positive inotropic effect of isoprenaline--mediated by beta-adrenoceptors--was affected to a lesser extent by D600 and the maximal response was not changed. It indicates that the stimulation of alpha- adrenoceptors in the rabbit papillary muscle induces a positive inotropic response through a biochemical process different from that caused via beta- adrenoceptors, i. e., stimulation of alpha- adrenoceptors may increase the intracellular calcium level mainly by changing the transmembrane calcium flux.

Animals↗
PubMed1972

Effects of perivascular nerve stimulation on the contraction and automaticity of the blood-perfused canine papillary muscle.

1. Effects of ventricular perivascular nerve stimulation (p.n.s.) on the ventricular contractility and idioventricular rate were investigated with the blood-perfused papillary muscle of the canine right ventricle.2. Perivascular nerve stimulation of supramaximal voltage and 1 msec pulse-duration caused a definite positive inotropic response at a frequency of 1 Hz, which gradually reached a maximum at 15 to 20 Hz when the papillary muscle was electrically driven at 120 beats/min at a constant temperature of 38-39 degrees C. The frequency-response curve was sigmoid.3. The spontaneous regular idioventricular rate of 46+/-4 beats/min was accelerated to at most 60+/-4 beats/min (n=11) by p.n.s. The stimulus frequency-response relations between chronotropic and inotropic responses to p.n.s. were almost the same.4. Tetrodotoxin blocked completely the responses to p.n.s. while it had little or no effect on the inotropic response to exogenous noradrenaline.5. Positive inotropic responses to p.n.s. were diminished by beta-adrenoceptor blocking agents (alprenolol, propranolol and pindolol) and were enhanced during infusion of cocaine.6. In reserpine- or guanethidine-pretreated muscles, p.n.s. as well as field stimulation produced negative inotropic responses, which were enhanced by physostigmine and were blocked by atropine.7. Hexamethonium enhanced slightly the positive inotropic responses to p.n.s. as well as field stimulation.8. It was concluded that the perivascular nerves of the coronary artery of the canine ventricle are mainly composed of postganglionic adrenergic fibres but there are also pre- and postganglionic cholinergic nerve fibres.

Alprenolol↗
PubMedDate not supplied

Pharmacological characteristics of endothelin receptors in the rabbit ventricular myocardium: the nonselective endothelin receptor antagonist PD 145065 antagonizes the positive inotropic effect of endothelin-3 but not of endothelin-1.

Endothelin-3 (ET-3) elicited a concentration-dependent positive inotropic effect on rabbit papillary muscle, the maximal response being approximately 65% of the maximal response to isoproterenol. ET-1 induced a positive inotropic effect over the concentration range below 10(-9) M, at which ET-3 did not produce a positive inotropic effect, but the maximal response to ET-1 was equivalent to or slightly lower than that of ET-3. The nonselective ET receptor antagonist PD 145065 effectively antagonized the positive inotropic effect of ET-3 in a concentration-dependent manner and abolished it at 10(-5) M. PD 145065 decreased the positive inotropic effect induced by ET1 at lower concentrations (< 10(-9) M) but it did not affect the main portion of the concentration-response curve for the positive inotropic effect, i.e., the effect induced by high concentrations (> 10(-9) M) of ET-1. PD 145065 antagonized also the positive inotropic effect of sarafotoxin S6c. PD 145065 inhibited the specific binding of [125I]ET-1 and of [125I]ET-3 with a high- and a low-affinity site for competition. ETB selective ligands, RES-701-1 and sarafotoxin S6c, displaced [125Iuc]ET-3 with high affinity but they scarcely affected the [125I]ET-1 binding. These findings indicate that different subtypes of the ET receptor are responsible for the induction of the positive inotropic effect of ET-3 and ET-1. ET receptors involved in the production of the positive inotropic effect in the rabbit ventricular myocardium have pharmacological characteristics that are different from those of conventional ET receptors originally classified based on the pharmacological findings in noncardiac tissues. The positive inotropic effect of ET-3 in the rabbit ventricular muscle may be mediated predominantly by ETA1 receptors that are susceptible to PD 145065 as well as BQ-123 and FR139317, and partially mediated by ETB receptors that are inhibitable with RES-701-1. ETA2 receptors that are resistant to ETA selective as well as nonselective antagonists may mainly be responsible for the positive inotropic effect of ET-1 in the rabbit ventricular muscle.

Animals↗