Positive inotropic action of dimethylamiloride in normal rat isolated hearts and papillary muscle and its primary mechanism / 中国药理学通报

Aim To study the inotropic action of DMA in normal rat isolated hearts and papillary muscle and search for its primary mechanism.Methods With Lansendorff-perfusion and isolated papillary muscle perfusion,cardiac performance and the systolic function of papillary muscle were measured to estimate the inotropic action of DMA;L-calcium channel blocker and sodium calcium exchanger(NCX)inhibitor were used to search for its primary mechanism.Results ①(1~20)?mol?L-1 DMA exerted a positive inotropic action in normal rat isolated hearts,that is in Langendorff-perfused hearts,DMA enhanced cardiac performance,i.e.LVSP-LVDP,+dp/dtmax,-dp/dtmax significantly(P

Effect of Tetrahydroisoquinoline Alkaloids on the alpha-adrenoceptors in Rat Aorta and Brain Homogenates

Tetrahydroisoquinoline(THI) alkaloids can be considered as cyclized derivatives of simple pthylamines and many of them, especially with 6,7-disubstitution, demonstrate relatively high affinity for catecholamines. In the present study, pharmacological action of limited series of THI has been examined using rat isolated atria and aorta. In addition, (H) prazosin displacement binding study with THI compounds using rat brain homogenates was performed to find out if these probes to have a-adrenoceptor affinity. In isolated rat atria, all THls and dobutamine increased heart rate and contractile force. In the presence of propranolol, the concentration response curves of YS 49 and YS 51 shifted to the right resulting in 8.07+0.84 and 7. 93+0.11 of pA values, respectively. The slope of each compound was not deviated from unity, indicating that these chemicals are highly competitive at the cardiac beta1-adrenoceptors. YS 49, YS 51 and higenamine showed alpha1- adrenoceptor affinity in rat brain in which the dissociation constant(K,) was 2.75, 2.81 and 1.02pM, respectively. It is concluded, therefore, that THI alkaloids have considerable affiniyt to alpha1-adrenoceptors in rat aorta and atria. while these probes show relatively high affinity for cardiac beta1-adrenoceptors. The authors speculate that it is worthy investigating whether these chemicals are useful in the management of vasospasm of aneurysmal subarachnoid hemorrhage.

Comparison of inodilator effect of higenamine, YS49, YS51, tetra-hydroisoquinoline analogs, and dobutamine in the rat

Tetrahydroisoquinoline (THI) alkaloids can be considered as cyclized derivatives of simple phenylethylamines. Many of them, especially with 6,7-disubstitution, demonstrate a relatively high affinity for catecholamines. Present study examines the pharmacological action of limited series of THI, using rats' isolated atria and aorta. In addition, a (3H) prazosin displacement binding study with THI compounds was performed, using rat brain homogenates to investigate whether these probes have a-adrenoceptor affinity. We also compared the vascular relaxation potency of these probes with dobutamine. YS 49, YS 51, higenamine and dobutamine, concentration-dependently, relaxed endothelium-denuded rat thoracic aorta precontracted with phenylephrine (PE, 0.1 micrometer) in which pEC50 were 5.56-0.32 and 5.55+/-0.21, 5.99+/- 1.16 and 5.57+/-0.34, respectively. These probes except higenamine also relaxed KCl (65.4 mM)-contracted aorta. In isolated rat atria, all THIs and dobutamine increased heart rate and contractile force. In the presence of propranolol, the concentration response curves of YS 49 and YS 51 shifted to the right and resulted in pA2 values of 8.07+/-0.84 and 7.93+/-0.11, respectively. The slope of each compound was not deviated from unity, indicating that these chemicals are highly competitive at the cardiac beta-adrenoceptors. YS 49 YS 51, and higenamine showed alpha-adrenoceptor affinity in rat brain, in which the dissociation constant (Ki) was 2.75, 2.81, and 1.02 micrometer, respectively. It is concluded, therefore, that THI alkaloids have weak affinity to alpha1-adrenoceptors in rat aorta and brain, respectively, while these probes show relatively high affinity for cardiac beta-adrenoceptors. Thus, these chemicals may be useful in the treatment of congestive heart failure.

CARDIOVASCULAR EFFECTS OF SOPHORAMINE / 中国药理学通报

Sophoramine ( Sa ) is an alkaloid from sophora alopecuroides. Linn., in anesthetize animals ( cat, rat and rabbit), intravenous adminstra-tion of Sa reduced rapidly and markly the arterial blood pressure. The mechanism of hypotension effect of Sa is mainly attributable to its sympathetic ganglionic blocking and direct vasodilatation. Experiment on the isolated hearts of guinea pig revealed that Sa produced negative chronotropic and positive inotropic action, and increased coronary flow simultaneously.In a study of experimental arrhythmia in animals,we observed that Sa could reduce the arrhythmia induced by aconitine in rats and decreased the incidence of ventricular fibrillation induced by chloroform in mice.

EFFECTS OF DEPHENETIN ON PERIPHERAL RESISTANCE AND CARDIOTONIC ACTION / 中国药理学通报

A study was made on the effects of Dephenetin on vascular resistance and cardiotonic action in anesthetized dogs. The results showed that Dephenetin reduced left coronary cifcumflexus, vertebral and femoral ateries resistance, it increased cardiac out put without significant heart rate changes.The results also showed that Dephenetin dilates peripheral vessels and produced positive inotropic action.