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T Akera

Publications and source records attributed to T Akera.

186 records · Page 11Linked to original sources
PubMedDate not supplied

Cassaine: mechanism of inhibition of Na+ +K+ -ATPase and relationship of this inhibition to cardiotonic actions.

The erythrophleum alkaloid cassaine shares many of the pharmacological actions of the cardiac glycosides but lacks the structural characteristics typical of cardiac glycosides. To further investigate the relationship between Na+ +K+ -ATPase inhibition and the cardiotonic actions of these drugs we investigated the interaction of cassaine with the Na+ +K+ -ATPase. Cassaine inhibited rat brain Na+ +K+ -ATPase with about one quarter of the apparent affinity of ouabain for this enzyme. This inhibition was non-competitive with respect to K+. Cassaine also inhibited this enzyme in the presence of Mg2+ and this inhibition was enhanced by Pi and antagonized by Na+. In the presence of Na+, Mg2+ and (gamma-32P)-ATP cassaine acted to stabilize the phosphorylated intermediate of Na+ +K+ -ATPase. Cassaine also acted to displace specifically bound (3H)-ouabain from this enzyme. These observations suggested that cassaine inhibited the Na+ +K+ -ATPase by interacting at the cardiotonic steroid binding sites of Na+ +K+ -ATPase. Consistent with this hypothesis, dog, guinea pig and rat heart Na+ +K+ -ATPase showed differing sensitivities to cassaine paralleling their differing sensitivities to ouabain. The principal difference between the interaction of cassaine and ouabain with Na+ +K+ -ATPase appeared to be the more rapid dissociation of cassaine from the cardiotonic steroid binding site(s) of Na+ +K+ -ATPase. In keeping with this the rates of offset of cassaine-induced inotropy in Langendorff perfused dog and guinea pig hearts were several times faster than those of ouabain-induced inotropy.

Abietanes↗
PubMedDate not supplied

The impact of side effects on hypertension management: a Japanese survey.

The purpose of this study was to assess medication compliance and to document side effects among a large number of Japanese patients receiving antihypertensive treatment. A total of 6289 patients being treated for hypertension returned completed questionnaires about their current blood pressure, therapy, side effects, and compliance with physicians' instructions. In addition, 4417 physicians returned completed questionnaires about their prescribing practices, side effects experienced by patients, and patient compliance. The antihypertensive agents they most often prescribed were calcium channel blockers, followed by angiotensin-converting enzyme inhibitors, beta-blockers, and diuretics. The proportion of patients who had well-controlled blood pressure, defined as systolic blood pressure < 160 mm Hg and diastolic blood pressure < 95 mm Hg, was similar regardless of the class of antihypertensive agent prescribed. Forty-nine percent of the patients with well-controlled blood pressure reported having at least one side effect while taking their current antihypertensive therapy, whereas a significantly greater percentage of patients (61%) with poorly controlled blood pressure reported side effects. Patients whose blood pressure was poorly controlled tended to have a higher incidence of most side effects than did those with well-controlled blood pressure. Also, the rate of intentional noncompliance was significantly higher in the group with poorly controlled blood pressure. In addition, the rate of noncompliance increased with the number of side effects reported. Although the causal relationship between side effects and non-compliance cannot be determined from this study, further investigation is warranted to better understand the impact these factors may have on overall cardiovascular morbidity and mortality.

Aged↗
PubMedDate not supplied

Cardiac actions of phencyclidine in isolated guinea pig and rat heart: possible involvement of slow channels.

The mechanisms responsible for the positive inotropic effect of phencyclidine were studied in isolated preparations of guinea pig and rat heart. In electrically paced left atrial muscle preparations, phencyclidine increased the force of contraction; rat heart muscle preparations were more sensitive than guinea pig heart muscle preparations. The positive inotropic effect of phencyclidine was not significantly reduced by a combination of phentolamine and nadolol; however, the effect was competitively blocked by verapamil in the presence of phentolamine and nadolol. Inhibition of the outward K+ current by tetraethylammonium chloride also produced a positive inotropic effect; however, the effect of tetraethylammonium was reduced by phentolamine and nadolol, and was almost insensitive to verapamil. The inotropic effect of phencyclidine was associated with a marked prolongation of the action potential duration and a decrease in maximal upstroke velocity of the action potential, with no change in the resting membrane potential. In partially depolarized atrial muscle preparations, which were reactivated by elevation of the extracellular Ca2+ level and stimulation at a high voltage, phencyclidine markedly increased the amplitude and the duration of the slow action potentials. Rat heart muscle preparations had higher sensitivity to these effects of phencyclidine. The specific [3H]phencyclidine binding observed with membrane preparations from guinea pig ventricular muscle was saturable with a single class of high-affinity binding site. This binding was inhibited by verapamil, diltiazem, or nitrendipine, but not by ryanodine or tetrodotoxin. These results suggest that the positive inotropic effect of phencyclidine results from enhanced Ca2+ influx via slow channels, either by stimulation of the channels or secondary to inhibition of outward K+ currents.

Animals↗
PubMedDate not supplied

Effect of ouabain on sodium movement in cardiac cells.

A computer simulation indicates that intracellular sodium concentration within a space near the inner surface of sarcolemma fluctuates during a cycle of myocardial function. The sodium transient (a transient increase in sodium ion concentration associated with membrane excitation) is enhanced by the inhibition of (Na+, K+)-ATPase by ouabain, but an accumulation of myocardial sodium does not occur until the inhibition exceeds a critical point. The critical magnitude of sodium pump inhibition that causes a progressive sodium accumulation is dependent on the heart rate.

Adenosine Triphosphatases↗