Hydro-alcoholic extract of Matricaria recutita exhibited dual anti-spasmodic effect via modulation of Ca2+ channels, NO and PKA2-kinase pathway in rabbit jejunum.

OBJECTIVE: Several studies have shown the antispasmodic activity of Matricariarecutita without detailing the underlying mechanism(s). The present study was designed to determine whether the antispasmodic mechanisms of M. recutita extract mediated via histaminergic/cholinergic receptors, Ca2+channels, activation of PKA2 and NO release in isolated rabbit jejunum. MATERIALS AND METHODS: The concentration- dependent (3 × 10-3-1.3 × 10-2 mg/ml) antispasmodic effect of the hydro-alcoholic extract of M. recutita flowers was studied in isolated rabbit jejunum. The isolated jejunum preparations were divided into seven groups, including the pharmacological probes that modulate cholinergic, histaminergic, and nitrergic receptors, as well as PKA2. RESULTS: M. recutita inhibited spontaneous smooth muscle contractility of the jejunum in a concentration-dependent manner (3 × 10-3-1.3 × 10-2 mg/ml) and reduced both K+- and Ca2+-induced contractions, which is similar to the effect of verapamil. The antispasmodic effect of M. recutita was inhibited by H89 (a PKA2 inhibitor). The myorelaxant effect of M. recutita increased in the presence of ACh/His and H89. CONCLUSION: M. recutita evoked antispasmodic and spasmolytic effects mediated through different signaling pathways. Our results have shown this dual inhibitory effect is mediated by blocking Ca2+ channels, activating His and ACh receptors, releasing NO, and activating PKA2.

The effects of serotonin on the electrophysiological properties of atrioventricular node during an experimental atrial fibrillation.

A few studies explored the atrioventricular (AV) nodal effects of 5-hydroxytyptamine (serotonin, 5-HT) during supraventricular tachyarrhythmia. The aims of the present study are to investigate (i) 5-HT effects on the rate-dependent electrophysiological functions of AV node during atrial fibrillation (AF) and (ii) the potential contribution of various 5-HT receptors and the role of the autonomic nervous system on 5-HT effects on AV nodal properties. The specific stimulation protocols were applied to detect the electrophysiological parameters of AV node in seven groups of isolated rabbit AV nodal preparations (N = 75) in the presence of 5-HT (0.5, 1, 5, 10, and 20 µM) and its receptor antagonists, nadolol and atropine. The simulated AF protocol was executed in a separate group, and specific indices, including mean His-His interval, a zone of concealment (ZOC), and concealed beats recorded. 5-HT (10-20 µM) increased significantly functional refractory period, Wenckebach cycle length, and excitability index (p < 0.05). The percentage of gap and echo beats was significantly decreased with increasing 5-HT concentrations (p < 0.05). Ketanserin and tropisetron increased significantly atrial-His conduction time, effective refractory period, and Wenckebach cycle length (p < 0.05). 5-HT effects on functional refractory period and Wenckebach cycle length were abrogated by tropisetron and nadolol (p < 0.05). 5-HT elicited prolongation of ZOC and nodal refractoriness (p < 0.05). We conclude that 5-HT elicited prolongation of the nodal refractoriness more than atrial-His conduction time leads to increase in the excitability index and ZOC without significant reduction of the ventricular rates during AF.

Frequency-dependent electrophysiological remodeling of the AV node by hydroalcohol extract of Crocus sativus L. (saffron) during experimental atrial fibrillation: the role of endogenous nitric oxide.

The study assessed the hydroalcohol extract effects of Crocus sativus L. (saffron) on (i) the basic and rate-dependent electrophysiological properties of the AV node, (ii) remodeling of the AV node during experimental atrial fibrillation (AF) and (iii) the role of nitric oxide (NO) in the effects of saffron on the AV node. Stimulation protocols in isolated AV node were used to quantify AV nodal recovery, facilitation and fatigue in four groups of rabbits (n = 8-16 per group). In addition, the nodal response to AF was evaluated at multiple cycle lengths and during AF. Saffron had a depressant effect on AV nodal rate-dependent properties; further, it increased Wenckebach block cycle length, functional refractory period, facilitation and fatigue (p < 0.05). A NO-synthase inhibitor (L-NAME) prevented the depressant effects of saffron on the AV node (p < 0.05). Saffron increased the zone of concealment in experimental AF (p < 0.05). The present research showed, for the first time, established electrophysiological remodeling of the AV node during AF by saffron. Saffron increased the AV nodal refractoriness and zone of concealment. These depressant effects of saffron were mediated by endogenous NO.