Vasodilatory effects of cinnamaldehyde and its mechanism of action in the rat aorta

Abstract

The vasodilatory effect of cinnamaldehyde was investigated for its mechanism of action using isolated rings of rat aorta. Cinnamaldehyde relaxed aortic rings precontracted with phenylephrine in a dose-dependent manner, was not affected by either the presence or removal of the endothelium. Pretreatment with NG-nitro-L-arginine methyl ester and 1H-[1,2,4]-oxadiazole-[4,3-a]-quinoxalin-1-one could not block vasodilation by cinnamaldehyde, indicating that nitric oxide signaling is not involved. Potassium channel blockers, such as glibenclamide, tetraethylammonium, and BaCl2, had no effect on the relaxation produced by cinnamaldehyde. In addition, treatment with either indomethacin or propranolol did not affect cinnamaldehyde-induced vasodilatation. On the other hand, pretreatment of endothelium-denuded rings with cinnamaldehyde significantly inhibited vasoconstriction induced by endogenous vasoconstrictors, including angiotensin II, 5-hydroxytryptamine, dopamine, endothelin-1, and phenylephrine. In a Ca2+-free experimental setting, this natural vasodilator not only blocked Ca2+ influx-dependent vasoconstriction by either phenylephrine or KCl, but also inhibited phenylephrine-induced tonic contraction, which relies on intracellular Ca2+ release. This study shows that endothelium-independent, Ca2+ influx and/or an inhibitory release mechanism contributes to the vasodilatory effect of cinnamaldehyde.

Keywords: cinnamaldehyde; endothelium; vascular smooth muscle cell; vasodilation.

Figures

Figure 1

A) The Cinnamomum cassia plant. B) The chemical structure of cinnamaldehyde.

Figure 2

Concentration-response curves showing dilation by acetylcholine of endothelium-intact and endothelium-denuded rings. Acetylcholine induced endothelium-dependent relaxation at the indicated dose in phenylephrine precontracted rat aortic rings (n = 6).

Figure 3

Dose-dependent vasodilatory effect of cinnamaldehyde on rat aorta rings. Cinnamaldehyde dilated both endothelium-intact and endothelium-denuded rings precontracted with phenylephrine, in a dose-dependent manner. The effect of cinnamaldehyde on this dilation was not different between the two groups (A, n = 6). Endothelium-intact rings preincubated with NG-nitro-L-arginine methyl ester (L-NAME) 10−4 M or indomethacin 10−5 M did not affect cinnamaldehyde function (B, n = 6). Endothelium-denuded rings preincubated with 1H-[1,2,4]-oxadiazole-[4,3-a]-quinoxalin-1-one (ODQ) 10−5 M did not inhibit the effects of cinnamaldehyde (C, n = 6).

Figure 4

Effect of cinnamaldehyde on K+ channels and the β-receptor. After preincubation with tetraethylammonium 3 × 10−3 M, BaCl2 10−4 M, or glibenclamide 10−5 M for 25 minutes, the effects of cinnamaldehyde were not inhibited by tetraethylammonium (A, n = 6), BaCl2 (B, n = 6), or glibenclamide (C, n = 6). After preincubation with propranolol 10−5 M, the vasodilatory effect of cinnamaldehyde was not inhibited (D, n = 6).

Figure 5

Concentration-response curves showing the vasoconstriction of dopamine A), 5-hydroxytryptamine B), angiotensin II C), endothelin-1 D), and phenylephrine E) in the absence or presence of cinnamaldehyde (Cin). The contraction curves of all the vasoconstrictors can be inhibited by cinnamaldehyde at the indicated concentration. Notes: *P < 0.05 versus controls, #P < 0.01 versus controls, n = 6.

Figure 6

Effect of cinnamaldehyde on the Ca2+ channel. Rat aortic rings were preincubated with or without cinnamaldehyde for 10 minutes, and the curves of CaCl2 in Ca2+-free solution containing 10−4 M EGTA and 60 mM KCl were inhibited by cinnamaldehyde (A, #P < 0.01 versus controls, n = 6). Comparison of contraction percentage between the cinnamaldehyde-preincubated and control groups on cumulative concentration-response curves of KCl. The constriction curve of KCl was inhibited by cinnamaldehyde (B, *P < 0.05 versus control, #P < 0.01 versus control, n = 6). Effect of cinnamaldehyde on the transient contraction effect of phenylephrine in Ca2+-free solution containing 10−4 M EGTA. With cinnamaldehyde preincubation for 10 minutes, the contraction effect of phenylephrine in Ca2+-free solution was inhibited by cinnamaldehyde (C, #P < 0.01 versus controls, n = 6).