The Curcumin-Induced Vasorelaxation in Rat Superior Mesenteric Arteries.

BACKGROUND

Curcumin (Cur) is a natural lipophilic polyphenol compound extracted from the rhizome of turmeric. Recently, protective effect of Cur on cardiovascular system is paid close attention. Some researches demonstrated that Cur could induce vascular relaxation in many arterial beds. However, relaxant effect of Cur on rat superior mesenteric artery is not clear. This present study will investigate the vasorelaxant effect of Cur on rat superior mesenteric arteries and the mechanisms involved.

METHODS

The isometric tension of rat superior mesenteric arterial rings was recorded by a sensitive myograph system in vitro. The vasodilation of Cur at various concentrations (range: 10-10 M) on potassium chloride (KCl; 60 mmol/L)-precontracted or phenylephrine hydrochloride (PE; 10 μmol/L)-precontracted arterial rings were observed. We also observed vasorelaxant effect of Cur on KCl (60 mM)-preconstricted rat superior mesenteric arterial rings after incubating the inhibitors of endothelial mechanism, including the endothelial nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester, the guanylate cyclase inhibitor 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one, and the cyclooxygenase inhibitor indomethacin, and inhibitors of potassium ion channel, including 4-aminopyridine (Voltage-sensitive K channel blockers), and tetraethylammonium chloride (Ca activated K channel blockers), and BaCl (Inward rectifying K channel blockers), and glibenclamide (ATP -sensitive K channel blockers), respectively. The effects of Cur are expressed as percentage of relaxation from the precontraction induced by KCl (60 mmol/L) or PE (10 μmol/L). The E value refers to the maximum relaxation. The pD value refers to the negative logarithmic value of the drug concentration that produces 50% E.

RESULTS

Cur concentration dependently relaxed the superior mesenteric artery rings with endothelium precontracted by PE (E = 84.33 ± 1.11 and pD = 5.03 ± 0.02) or KCl (E = 80.96 ± 2.12% and pD = 4.32 ± 0.01). The vasorelaxant effect of Cur on the superior mesenteric artery rings relied on endothelium partially. Indomethacin (5 μM) significantly inhibited the effect. However, 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (10 μM) and Nω-nitro-L-arginine methyl ester (100 μM) had no effect on the action. In artery rings without endothelium, vasorelaxation induced by Cur was attenuated by 4-aminopyridine (100 μM). However, barium chloride dehydrate (10 μM), glibenclamide (10 μM), and traethylammonium chloride (1 mM) did not affect vasorelaxation induced by Cur. Moreover, Cur also significantly inhibited contraction induced by increasing external calcium in Ca-free medium plus K (60 mM) and releasing intracellular Ca in the Ca-free solution.

CONCLUSIONS

Our results suggested that Cur induces relaxation in superior mesenteric arterial rings through an endothelium-dependent pathway, involving prostanoid, and also through an endothelium-independent pathway, opening K channel, and blockade of Ca influx and intracellular Ca release.