Possible mechanisms of action of the hypotensive effect of Annona muricata (soursop) in normotensive Sprague-Dawley rats.

CONTEXT: Annona muricata Linn (Annonaceae) (soursop) is a food plant reported to have antihypertensive properties. OBJECTIVE: We investigated the blood pressure reducing effect of its aqueous leaf extract and the possible mechanisms that may be responsible. METHODS: Intravenous administration of an aqueous leaf extract (9.17-48.5 mg/kg) of A. muricata on the mean arterial pressure and heart rate were recorded invasively on anaesthetized, normotensive Sprague-Dawley rats. Contractile responses of rat aortic rings to the extract (0.5-4.0 mg/mL) were studied using standard organ bath techniques. RESULTS: A. muricata (9.17-48.5 mg/kg) caused significant (p < 0.05) dose-dependent reduction in blood pressure without affecting the heart rates. The hypotensive effects were unaffected by atropine (2 mg/kg), mepyramine (5 mg/kg), propranolol (1 mg/kg) and L-NAME (5 mg/kg). A. muricata leaf aqueous extract significantly (p < 0.05) relaxed phenylephrine (10(-9)-10(-4) M) and 80 mM KCl induced contractions in endothelium intact and denuded aortic rings; and caused a significant (p < 0.05) rightward shift of the Ca(2+) dose response curves in Ca(2+)-free Kreb's solution containing 0.1 mM EGTA. CONCLUSIONS: The hypotensive effects of A. muricata are not mediated through muscarinic, histaminergic, adrenergic and nitric oxide pathways, but through peripheral mechanisms involving antagonism of Ca(2+).

Possible mechanisms of action of the aqueous extract of Artocarpus altilis (breadfruit) leaves in producing hypotension in normotensive Sprague-Dawley rats.

CONTEXT AND OBJECTIVES: Artocarpus altilis (Parkinson) Fosberg (Moraceae) (breadfruit) leaves are used as an antihypertensive remedy. We investigated the possible mechanisms of action of its aqueous extract and its effect on cytochromes P450 (CYP) enzyme activities. MATERIALS AND METHODS: Intravenous administration of an aqueous leaf extract (20.88-146.18 mg/kg) of A. altilis on mean arterial pressure and heart rate were recorded via cannulation of the carotid artery on anaesthetized normotensive Sprague-Dawley rats. Recordings of the contractile activity of the aortic rings to the extract (0.71-4.26 mg/mL) were studied using standard organ bath techniques. Inhibitions of human CYP3A4 and CYP2D6 enzyme activities were evaluated by means of a fluorometric assay in 96 well plates using heterologously expressed microsomes. RESULTS: A. altilis caused significant (p < 0.05) hypotensive and bradycardiac responses unaffected by atropine (2 mg/kg) and mepyramine (5 mg/kg), but attenuated by propranolol (1 mg/kg) and N(G)-nitro-L-arginine methyl ester (5 mg/kg). The extract (0.71-4.26 mg/mL) significantly (p < 0.05) relaxed phenylephrine (10⁻9-10⁻4 M) and 80 mM KCl-induced contractions in endothelium intact and denuded aortic rings; and caused a significant (p < 0.05) rightward shift of the Ca²âº dose-response curves in Ca²âº-free Kreb's solution. Moderate inhibitions of cytochrome P450s (CYP3A4 and CYP2D6) enzyme activities with IC50 values of 0.695 ± 0.187 and 0.512 ± 0.131 mg/mL, respectively, were produced. CONCLUSION: A. altilis exhibits negative chronotropic and hypotensive effects through α-adrenoceptor and Ca²âº channel antagonism. Drug adversity effects are unlikely if the aqueous leaf extract is consumed with other medications reliant on CYP3A4 and CYP2D6 metabolism. This study thus provides scientific evidence for the use of the breadfruit in the treatment of hypertension.