Averrhoa bilimbi L. leaf Aqueous Extract Modulates both Cardiac Contractility and Frequency in the Guinea-pig Atrium by the Activation of Muscarinic Receptors

Background: Averrhoa bilimbi has been used in the traditional medicine for treatment of hypertension, diabetes and as an antihypercholesterolemic. This study investigated the inotropic and chronotropic effects of Averrhoa bilimbi aqueous extract (AqE) on the guinea pig atrium. Methods: Left and right atria isolated from guinea pig were used to evaluate the atrial contractility and atrial rate, respectively. Results: In left atria, AqE showed a negative inotropic effect and delaying the time to peak without change relaxation time. In right atria, AqE reduced the atrial rate (67%). Furthermore, AqE induced a rightward shift in the concentration-effect curve of CaCl2 and reduced by 61% the Bowditch phenomenon. To evaluate the mechanism involved in the effects evoked by AqE, concentration-effect curves were obtained in the presence of atropine (M2 muscarinic receptor antagonist) and TEA (non-selective potassium channels blocker). The results revealed that these antagonists shifted rightward the concentration-effect curve of AqE. Conclusion: In conclusion, AqE reduces both atrial contractility and heart rate by activation of M2 receptors increasing potassium efflux associated with decreased calcium entry in cardiomyocyte. These effects are important for its future pharmacological applications being a source of new drugs that can be use in treatment of cardiovascular disease.