Experimental cardiovascular depressant effects of garlic (Allium sativum) dialysate.

The objectives of this work were to investigate the effects of a garlic dialysate on diastolic blood pressure (DBP), heart rate (HR) and electrocardiogram (ECG) of anaesthetized dogs and its effects on frequency and tension of isolated rat atria. Garlic dialysate led to a drop in DBP (from 112.5 +/- 3.67 to 70 +/- 3.16 mmHg) and a decrease in HR (from 198 +/- 9.81 to 164 +/- 16.59 beats/min) in a dose-dependent manner. The ECG showed a regular sinus bradycardic rhythm. The addition of garlic dialysate to isolated left rat atria evoked a decrease in tension development. Frequency, measured by spontaneous beating of the right atria, was also reduced. Both effects were dose-dependent. In addition to these effects, the positive inotropism and chronotropism induced by addition of isoproterenol 10(-9) M, were partially antagonized by preincubation of the rat atria with the garlic dialysate. The above findings can be explained by a depressant effect on automaticity and tension development in the heart, suggesting a beta-adrenoceptor blocking action produced by the garlic dialysate.     

Effects of aqueous extract of Baphia nitida on isolated cardiac tissues

The pharmacological action of cold aqueous extract of fresh leaves of Baphia nitida was studied on cardiac preparations. The extract (5.0 × 10^?3 g mL) reduced the rate and force of contraction of the isolated rabbit heart. The rate and force of contraction of the spontaneously beating rat atria was dose-dependently reduced by 5.0 × 10^?4 to 2.5 × 10^?2 g/mL of the extract and this effect was not antagonized by 3.45 × 10^?7 M atropine. The extract (5.0 × 10^?2 g mL) completely blocked the positive chronotropic and inotropic effects of 10 mM CaCI² but only reduced that of 1.61 × 10^?7 M isoprenaline. The effect of the extract on CaCI₂-induced responses of the rat atria was not affected by 3 × 10^?7 M propranolol. The use of this extract for treating palpitation locally may be related to its negative chronotropic and inotropic effects.     

Cardiovascular effects of plant secondary metabolites norarmepavine,coclaurine and norcoclaurine

The cardiovascular effects of (±)-norarmepavine, a benzylisoquinoline alkaloid of natural origin, have been determined on anaesthetized rats in vivo, on spontaneously beating atria and on aortic smooth muscle. In aorta, the effects of (±)-coclaurine and (±)-norcoclaurine, benzylisoquinolines with a related structure, were also compared. (±)-Norarmepavine (10 mg/kg i.v.) decreased the mean arterial pressure and heart rate by 45% and 21%, respectively. (±)-Norarmepavine (10⁻⁵–10⁻³ M ) showed a negative chronotropic effect on rat-isolated atria, decreasing the spontaneous frequency by about 54%. Aortic rings contracted with KCl 70 mM were relaxed in a concentration-dependent manner by (±)-norarmepavine, (±)-coclaurine and (±)-norcoclaurine (10⁻⁶–10⁻³ M ). The two earlier alkaloids exhibited an efficacy similar to verapamil, relaxing the aortic rings by 100%. (±)-Norcoclaurine exhibited a lower efficacy. These results point to the importance of methylation of these compounds. The rank order of potency was: (±)-verapamil > (±)-norarmepavine > (±)-norcoclaurine > (±)-coclaurine. The alkaloids shifted to the right the calcium-dependent contraction curves, denoting a calcium antagonist-like effect; however, only a 10-fold increment of (±)-norcoclaurine concentration produced an equivalent effect. Our results demonstrate the hypotensive and bradycardic properties of (±)-norarmepavine. It is proposed that this alkaloid could somehow modulate calcium entry, its intracellular release or the calcium sensitivity of the cell contractile-machinery, previously postulated for coclaurine. (±)-Norcoclaurine effects reported here are not in agreement with the proposal of (±)-norcoclaurine as a calcium channel activator or β₁-adrenoceptor agonist. © 1998 John Wiley & Sons, Ltd.     

Pharmacological screening of (+)-Multifloramine from Colchicum decaisnei

(+)-Multifloramine (1) isolated from Colchicum decaisnei (Liliaceae) exhibited significant positive inotropic and negative chronotropic effects on isolated rat atria. The positive inotropic effect was not antagonized by adding propranolol. The compound showed hypotensive and tocolytic activities. The LD₅₀ of the compound in mice was found to be 383 mg/kg body weight. Its quaternary methiodide derivative (2) produced less effect on atria, uterus and mean arterial blood pressure. The LD₅₀ of the derivative in mice was 31.6 mg/kg body weight.     

槐花对家兔体外心房肌的作用

目的 :观察槐花对家兔体外心房肌生理特性的影响 ,并探讨其作用机制。方法 :运用体外心脏实验法 ,摘取家兔心房肌 ,观察测定给药前后体外心房肌的收缩力、心率、功能性不应期、静息后加强及正性阶梯效应的变化。结果 :槐花煎液能显著降低心肌收缩力、减慢心率 ,阿托品可抑制槐花的负性心率作用 ,但不能抑制其负性肌力作用 ;槐花煎液可显著减弱家兔体外左心房肌的正性阶梯作用 ,并显著延长功能性不应期 ,但不影响静息后加强效应。结论 :槐花对心肌具有负性肌力和负性频率作用 ,其作用机制与其抑制胞外 Ca2 +跨膜内流有关。     

Effects of crinum glaucum aqueous extract on intestinal smooth muscle activity

Crinum glaucum aqueous extract (1–8 mg/mL) produced a concentration dependent, non-competitive inhibition of contractions induced by acetylcholine (1.1 × 10⁻⁸–3.3 × 10⁻⁷M ) and calcium chloride (CaCl₂, 0.05–2 mM ) on the rat duodenum. Contractions of the guinea-pig ileum induced by acetylcholine (1.1 × 10⁻⁸–3.3 × 10⁻⁷M ) and histamine (1.1 × 10⁻⁸–3.3 × 10⁻⁷M ) were inhibited by the extract (1–4 mg/mL). The extract (0.125–2.0 mg/mL) also, produced a concentration dependent relaxation of the guinea-pig taenia coli, precontracted with potassium chloride (40 mM ). It is concluded that the extract is a non-specific relaxant of the gastrointestinal smooth muscles used. © 1998 John Wiley & Sons, Ltd.     

Effects of Olea europaea L. extract on the rat isolated ileum and trachea

The effects of an Olea europaea L. dried leaf extract containing 3.2% of oleuropein were investigated on the rat isolated ileum and trachea. On basal tone rat isolated ileum, Olea europaea L. extract was shown to produce a dual effect characterized by a contraction at low doses (10^?7-10^?4g/mL) and a relaxation at high doses (3.10^?4-10^?3g/mL). The extract induced contractile effect was found to involve at least histamine, 5-hydroxytryptamine and thromboxane A₂. On precontracted rat isolated ileum, the extract only induced a relaxation that was not modified by nifedipine, diltiazem, dipyridamone, verapamil or papaverine (10^?6 M). The effects of the extract were also studied on the rat isolated trachea. On basal tone organs, Olea europaea L. extract did not produce any effect, whereas, when basal tone was raised by acetylcholine (ACh 10^?3 M), the drug caused a relaxation (maximal effect 39.01% ± 5.40%) of the response to theophylline; (3.10 ± 10^?3M n = 15). It is suggested that the induced relaxation is consecutive to an increase of intracellular 3′5′ cAMP.     

Bioactive substances from the Chinese daffodil,Narcissus tazetta

The cardiovascular activity of the aqueous (A) and 30% MeOH (B) fractions of an ethanol extract of the daffodil bulbs (Narcissus tazetta) was examined using in vivo and in vitro preparations of normotensive rats and in the presence/absence of various blockers: α, β-adrenergic, cholinergic, ganglionic, histaminergic, enzyme converson inhibitor, calcium channel. These fractions (A and B) produced similar dose-dependent hypotensive responses in the anesthetized animals. The responses induced by fraction B might be mediated via adrenergic and cholinergic receptor activation. In isolated atrial preparations, fraction A increased the atrial rate (+ ve chronotropism) but not the atrial tension (inotropism). Fraction B, however, produced negative chronotropic but positive inotropic responses. Fraction B had no effect on the untreated tail vascular smooth muscle but increased the tension on AVP-preconstricted helical strips. It is suggested that the daffodil bulb contains cardiovascular active substances, the sum total of the effects produced accounts for the hypotensive action. It is further shown that these substances are distinct from those of well-documented antimitotic narciclasine.     

Ginseng–Aconite Decoction elicits a positive inotropic effect via the reverse mode Na/Ca exchanger in beating rabbit atria

Ethnopharmacological relevance

Ginseng–Aconite Decoction (GAD), a traditional oriental medicine composed of Panax ginseng C.A. Mey. (Araliaceae) and Aconitum carmichaeli Debx. (Ranunculaceae) has been used as treatment for cardiovascular diseases from Song Dynasty of China. The purpose of the present study was to elucidate the possible mechanisms of GAD-induced positive inotropic effect.

Material and methods

GAD-induced changes in atrial dynamics and cAMP efflux were determined in isolated perfused beating rabbit atria.

Results

GAD significantly increased atrial dynamics such as stroke volume, pulse pressure and augmented cAMP efflux in beating rabbit atria. The inotropic effect was significantly attenuated by pre-treatment with KB-R7943, a reverse mode Na⁺/Ca²⁺ exchanger blocker. The GAD-induced increase in atrial dynamics was also markedly inhibited by staurosporine, a non-selective protein kinase inhibitor, and partly blocked by KT5720, a selective PKA inhibitor. The effect of GAD on atrial dynamics was not altered by pre-treatment with propranolol, a β-adrenergic receptor inhibitor, or diltiazem, an L-type Ca²⁺channel blocker. The phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX) failed to modulate the GAD-induced increase in atrial dynamics, but markedly attenuated cAMP efflux in the beating atria.

Conclusion

These results suggest that the GAD-induced positive inotropic effect in beating rabbit atria may be attributable to stimulation of the reverse mode Na⁺/Ca²⁺ exchanger, while PKA activity would, at least in part, be participated in the course.     

Aqueous extract of Zanthoxylum schinifolium elicits contractile and secretory responses via β1-adrenoceptor activation in beating rabbit atria

Aim of study

Although Zanthoxylum schinifolium has long been used in the traditional oriental medicine, cardiac effects have not well been documented. The aim of the present study was to investigate the effects of aqueous extract of leaves and stems from Zanthoxylum schinifolium (AZS) on inotropic effect and atrial natriuretic peptide (ANP) secretion.

Materials and methods

The AZS-induced changes in atrial dynamics, cAMP efflux and atrial ANP secretion were determined in isolated perfused beating rabbit atria.

Results

AZS increased atrial pulse pressure, stroke volume, and cAMP efflux concomitantly with inhibition of ANP secretion in a concentration-dependent manner. The AZS-induced increases in atrial dynamics and cAMP efflux, and decrease in ANP secretion were attenuated by pretreatment with propranolol and CGP 20712 but not ICI 118,551. Also, the AZS-induced changes in atrial dynamics and ANP secretion were attenuated by diltiazem and KT 5720. Diltiazem and KT 5720 had not significant effect on the AZS-induced increase in cAMP efflux.

Conclusion

These results suggest that AZS elicits a positive inotropic effect and decrease in ANP secretion via β₁-adrenoceptor-cAMP-Ca²⁺ signaling in beating rabbit atria.     

The interactions of paeoniflorin and veratrine on isolated rat atria

In this study, we attemped to identify the interactions and mechanisms between veratrine and paeoniflorin on isolated rat atria. Paeoniflorin alone showed no effect on the rat atria. Veratrine increased the atrial contraction and induced arrhythmia at 1×10⁻⁵ g/ml. Veratrine could directly induce contraction and elicit tetanic contraction at 1×10⁻⁴ g/ml in the left atria with or without electric stimulation. Paeoniflorin (4.8×10⁻⁶ to 4.8×10⁻³ g/ml), verapamil (2.2×10⁻⁶ g/ml), tetrodotoxin (TTX) (3.2×10⁻⁸ g/ml) and quinidine (7.5×10⁻⁶ g/ml) inhibited the increase of contraction and delayed the onset of contraction induced by veratrine (1×10⁻⁵ g/ml). The inhibitory effect of paeoniflorin combined with verapamil on the contraction induced by veratrine was more potent than that of paeoniflorin or verapamil alone. However, the inhibitory effect of paeoniflorin was not potentiated by TTX or quinidine. From the above results, the contraction evoked by veratrine in the rat atria may be concluded to be caused by the stimulation of Na⁺- and Ca²⁺-ion channels. The inhibition of paeoniflorin on the contraction induced by veratrine may primarily be related to the blockade of Ca²⁺ channels.     

Terminalia arjuna,an ayurvedic cardiotonic,increases contractile force of rat isolated atria

The direct effects of aqueous, ethanolic, chloroform and petroleum ether extracts of Terminalia arjuna (family: Combretaceae) bark, an ayurvedic remedy for cardiovascular disorders, were studied on isolated atria of rats. The aqueous extract produced a substantial positive inotropic effect (EC₅₀ = 0.25 mg/mL) but no change in the rate. The ethanol, chloroform and petroleum ether extracts all decreased the rate of contraction. A slight increase in force was seen with ethanol and chloroform extracts. Higher concentrations of the chloroform extract had a negative inotropic effect. The ethanol extract decreased the maximum following frequency of the left atria. It is concluded that Terminalia arjuna has a significant positive inotropic property on rat atria in vitro which could contribute to its efficacy in treating cardiovascular disorders.     

Effect of an aqueous extract of Portulaca oleracea leaves on smooth muscle and rat blood pressure

An aqueous extract of Portulaca oleracea leaves and stems produced a dose-dependent relaxation of guinea pig fundus, taenia coli and rabbit jejunum and a dose-dependent contraction of the rabbit aorta. On spontaneously-beating rabbit right atria and electrically-paced left atria, the extract produced a dose-dependent negative inotropic and chronotropic effects. On rat blood pressure, the extract produced dose-dependent pressor responses. Phentolamine reduced the relaxant effect of the extract on gut smooth muscle and abolished the contractile response on the aorta as well as the pressor response on blood pressure. Guanethidine and tetrodotoxin had no effect on extract-induced relaxant or contractile responses. On rat blood pressure atropine and cyproheptadine had no effect on extract-induced pressor response, whereas propranolol slightly reduced the pressor response. An increase in extracellular calcium reversed the inhibitory effect of the extract on the rabbit atria. The extract may, therefore, act in part on postsynaptic alpha-adrenoceptors and by interference with transmembrane calcium influx.     

白藜芦醇对豚鼠离体心房肌收缩力和心率的影响

目的：观察白藜芦醇(resvaratrol,Res)对豚鼠离体心肌收缩力(contraction force,CF)和窦房结功能的影响。方法：测定Res对离体豚鼠心房肌CF和心率(heart rate,HR)影响的量效曲线,并研究不同类型钾通道阻断剂在Res对心脏负性变时变力作用的影响。结果：Res可减慢心率(P<0.05),减弱心肌CF (P<0.05)；与Res组相比,ATP敏感性钾通道(K_ATP)阻断剂格列苯脲(Glibenclamide,Gli)、钙激活钾通道(K_Ca)阻断剂四乙胺(tetraethylammonium,TEA)可部分阻断Res的作用(P<0.05),电压依赖性钾通道(K_V)阻断剂4-氨基吡啶(4-aminopyridine,4-AP)、内向整流钾通道(K_IR)阻断剂氯化钡(barium chloride,BaCl₂)、乙酰胆碱(ACh)调节钾通道(K_ACh)阻断剂阿托品(Atropine)不能阻断Res的作用。结论：Res可呈剂量依赖性减慢HR、减弱CF,其作用是通过开放K_ATP及K_Ca有关,与K_V,K_IR和K_ACh无关。     

A drug used in traditional medicine: Harpagophytum procumbens DC II. Cardiovascular activity

In conscious normotensive rats the dried crude methanolic extract of Harpagophytum procumbens secondary roots caused a significant dosedependent reduction of arterial blood pressure. The decrease was significant only at higher doses given by gavage (dried extract = 400 $\text{mg}\text{kg}$). At the same time a decrease of heart rate was observed.In the same experimental conditions, harpagoside presented an activity lower than doses of Harpagophytum procumbens extract containing corresponding quantities of harpagoside.In spontaneously beating Langendorff preparations of rabbit heart, the Harpagophytum procumbens methanolic extract caused a mild decrease in the heart rate with a concomitant mild positive inotropic effect at lower doses but a marked negative inotropic effect at higher doses. The coronary flow decreased at higher doses only.The negative chronotropic and positive inotropic effects of harpagoside were comparatively higher with respect to that of the extract, whereas harpagide had only a slight negative chronotropic effect and a considerable negative inotropic one.Both in experiments on intact rats and on isolated rabbit heart, the Harpagophytum procumbens extract also demonstrated a protective action with regard to arrhythmias induced by aconitine, and particularly to those provoked by calcium chloride and epinephrine—chloroform.     

Pharmacological Actions of Naringin on Alpha,Beta-adrenoceptors and Uptake of Noradrenaline in Rat Isolated Vas Deferens

In normal Krebs solution, naringin (1×10⁻⁷ M sc–2×10⁻⁶ M ) enhanced noradrenaline-induced contractions in rat isolated vas deferens increasing this potentiation in a concentration dependent manner. This enhancing effect continued in the presence of yohimbine (10⁻⁶ M ) or propranolol (10⁻⁶ M ). Naringin did not modify significantly the dopamine dose-response curves. In a medium containing 10⁻⁸ M prazosin, naringin decreased noradrenaline dose-response curves underneath the control curve at all the doses tested. Naringin did not modify significantly the NA dose-response curve in a medium containing cocaine (10⁻⁵ M ) or oestradiol (10⁻⁵ M ). The potentiation produced by naringin on the NA-induced contractions in rat vas deferens may be due to alpha-1 receptor activation, together with an interference of naringin in catecholamine uptake process.     

Inhibitory effects of Cistus populifolius on contractile responses in the isolated rat duodenum

The medicinal plant Cistus populifolius L., shows an important dose-dependent spasmolytic activity. The ability of the Cistus extract to inhibit both acetylcholine (ACh) (3.4 × 10⁻⁸–6.8 × 10⁻⁵ M) and CaCl₂ (2 × 10⁻⁴–1.28 × 10⁻² M) -induced contractions and the relaxing effect on K⁺ (75 mM) -induced contractions may indicate a non-specific receptor antagonist. However, this action may be related to the influx of extracellular Ca²⁺. These antispasmodic effects are partly consistent with the use of C. populifolius in folk medicine for certain gastrointestinal disorders.     

Phytochemical and pharmacological investigation of the cardioactive constituents of the leaf of Dysoxylum lenticellare

The cardiac effects of the leaf extract and 11 isolated pure compounds have been examined on isolated, spontaneously beating, atrial muscles of the rat. Using nor-adrenaline (8 X 10(-7)M) and acetylcholine (4 X 10(-8)M) as reference drugs and normal saline (equivalent volume) as control, the crude extract of Dysoxylum lenticellare (8 X 10(-4) g/ml) induced negative chronotropic and positive inotropic responses on the isolated cardiac muscle preparations. The extract demonstrated significant (p less than 0.05-0.01) cardioactivity as attested to by its positive inotropic and/or negative chronotropic activities on the rat atrial preparations. Of the pure isolates tested, 7, 8, and 9 demonstrated significant cardiac effects. Although the precise mechanism of action of the extract or pure isolates on the atrial myocardium has not been fully determined, available experimental data suggest that the extract and pure isolates act directly on the cardiac muscle. Alkaloids 7, 8, and 9 manifest cardiac effects similar to that of the crude extract but of lesser magnitude. Some indirect effects of these isolates may, however, be associated with the manifested activities.     

The hypotensive action of Desmodium styracifolium and Clematis chinensis

The cardiovascular pharmacology of aqueous extracts of Desmodium styracifolium (DSE) and Clematis chinensis (CCE) were studied in rats both in vivo and in vitro. DSE produced two successive hypotensive actions: the first one via cholinergic receptor stimulation, while the second one potentiated by blockades of autonomic ganglion and alpha-adrenoceptor. In contrast to DSE, CCE produced only one hypotensive response which was mediated through histaminergic activity. Furthermore, both extracts relaxed isolated methoxamine preconstricted helical tail artery strips. CCE also produced both negative chronotropic and inotropic effects on isolated atria, while DSE was positive chronotropic without apparent effect on the contractile force.     

Effects of an aqueous extract of Terminalia arjuna on isolated rat atria and thoracic aorta

Terminalia arjuna (Combretaceae) is used traditionally in ayurveda, to treat a variety of cardiovascular disorders. The aims of this study were to characterize the positive inotropic effect of the aqueous extract of T. arjuna bark in isolated paced rat left atria and to study its effects on a vascular smooth muscle preparation, the rat thoracic aorta. The crude and semipurified aqueous extracts produced a positive inotropic effect of rat atria and the maximum contraction was comparable to that produced by isoprenaline. The positive inotropic effect of the extract was completely blocked by a β-adrenoceptor blocker, propranolol, and an uptake-1 blocker, cocaine. In precontracted aorta, the aqueous extract produced a contraction followed by relaxation. Propranolol did not block the relaxant effect of the aqueous extract. It is concluded that the positive inotropic effect of the aqueous extract was mediated via an action on β₁-adrenoceptors and was likely to be due to the release of noradrenaline from the sympathetic nerve endings. The vasorelaxant effect of the extract, however, was not mediated via an action on β₂ adrenoceptor.