Hypotensive and endothelium-independent vasorelaxant effects of methanolic extract from Curcuma longa L. in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma longa L. (CL) is a yellow rhizome that is used in African traditional medicine to treat palpitation, hypertension or other related blood circulation disorders. AIM OF THE STUDY: To justify the use of CL in ethnomedicine, we investigated the vasorelaxant effect of methanolic extract of CL (CLME) and its underlying mechanisms in isolated rat mesenteric artery. MATERIALS AND METHODS: The effect of CLME on the mean arterial pressure (MAP) and heart rate (HR) (pulse interval) were determined in vivo in non-anaesthetized rats. Superior mesenteric rings were isolated, suspended in organ baths containing Tyrode solution at 37 degrees C and gassed with 95% O(2)+5% CO(2), under a resting tension of 0.75 g. The vasorelaxant effects of CLME were studied by means of isometric tension recording experiments. RESULTS: In normotensive rats, CLME (10, 20 and 30 mg/kg, i.v.) induced dose-dependent hypotension (2.0+/-0.5%; 27.1+/-5.0% and 26.7+/-4.6%, respectively), and pronounced bradycardia (5.8+/-1.2%, 19.3+/-3.2% and 22.9+/-4.6%, respectively). CLME (1-1000 microg/mL) induced concentration-dependent relaxation of tonic contractions evoked by phenylephrine (Phe) (10 microM) and KCl (80 mM) in rings with intact-endothelium (E(max)=82.3+/-3.2% and 97.7+/-0.7%) or denuded-endothelium (E(max)=91.4+/-1.0% and 97.8+/-1.1%). Also, in a depolarized, Ca(2+) free medium, CLME inhibited CaCl(2) (1 microM-30 mM)-induced contractions and caused a concentration-dependent rightward shift of the response curves, indicating that CLME inhibited the contractile mechanisms involving extracellular Ca(2+) influx. In addition, in Ca(2+) free media containing EGTA (1 mM), CLME inhibited the transient contraction of denuded rings constricted with Phe, but not those evoked by caffeine (20 mM). In contrast, neither glibenclamide, BaCl(2), tetraethylammonium nor 4-aminopyridine affected CLME-induced relaxation. CONCLUSIONS: These results demonstrate the hypotensive and bradycardic effects of CLME, as well as its potent vasodilation of rat mesenteric arteries. These effects, may in part, be due to the inhibition of extracellular Ca(2+) influx and/or inhibition of intracellular Ca(2+) mobilization from Phe-sensitive stores.

Endothelium-independent vasodilation induced by kolaviron, a biflavonoid complex from Garcinia kola seeds, in rat superior mesenteric arteries.

Previous studies have established the hepatoprotective, gastroprotective, hypolipidemic and hypoglycemic effects of kolaviron (KV), a biflavonoid complex from Garcinia kola seeds. In this study, we investigated the mechanisms involved in the vasorelaxant effects of KV in isolated superior mesenteric arteries from normotensive rats. KV (1, 10, 30, 100, 300, 500 and 1,000 microg/ml) concentration-dependently inhibited the contractions induced by phenylephrine (PHE) (10 microM) and KCl (80 mM) in both endothelium-intact (E(max) = 58.3 +/- 1.7% and 51.4 +/- 1.3%, respectively) and -denuded rings (E(max) = 59.3 +/- 5.5% and 64.3 +/- 2.4%, respectively). Furthermore, KV reduced CaCl(2)-induced contraction in Ca(2+)-free medium containing KCl 60 mM, thus acting as a Ca(2+)-antagonist. In addition, KV inhibited the transient contraction by PHE in Ca(2+)-free medium containing EGTA, suggesting a possible action on the release of intracellular Ca(2+) via the inositol-1,4,5-triphosphate (IP(3)) pathway. KV is not a specific alpha-adrenoceptor blocker, since it also caused a concentration-dependent inhibition of contractile responses to KCl, suggesting that KV also blocks the L-type Ca(2+)-channel. As a Ca(2+) antagonist, KV (100 microg/ml) potentiates the relaxant effects of nifedipine in denuded rings (E(max) = 97.6 +/- 1.2%; control = 75.1 +/- 3.0%, P<0.05). Also, the vasorelaxation induced by KV was significantly inhibited after pre-treatment of the denuded rings with 4-aminopyridine (4-AP) 1 mM, a selective blocker of voltage-dependent K(+) (K(v)) channels and, tetraethylammonium (TEA) 1 mM or charybdotoxin (ChTX) 0.1 microM, non-selective blockers of large and intermediate conductance Ca(2+)-activated K(+) (BK(Ca)) channels. In contrast, neither glibenclamide (10 microM), BaCl2 (1 mM) nor apamin (0.1 microM), blockers of K(ATP), K(IR) and SK(Ca) channels, respectively affected the KV-induced vasorelaxation. In conclusion, our results provide functional evidence that the vasorelaxant effects by KV involve extracellular Ca(2+) influx blockade, inhibition of intracellular Ca(2+) release and the opening of K(+) channels sensitive to 4-AP and ChTX with a resultant membrane hyperpolarization/ repolarization.