Blood-Pressure-Lowering and Endothelium-Dependent Vasorelaxant Effects of Nutgall Tree in Rats

Abstract

Hypertension is the crucial modifiable risk factor for cardiovascular diseases, and efforts to identify functional foods that are effective for hypertension control are increasing. The nutgall tree (NT, Rhus chinensis Mill.) is used in traditional medicine and food because of its medicinal value. However, the role of NT in hypertension has not been investigated. Therefore, the hypotensive effect of NT leaf ethanol extract (NTE) was investigated in spontaneously hypertensive rats (SHRs). SHRs were allocated to three groups (control, 300, or 1000 mg/kg NTE), and blood pressure was measured before and after oral administration. Systolic and diastolic blood pressure significantly decreased in the NTE 1000 mg/kg group and was the lowest at 2 h after administration (-26.4 ± 10.3, -33.5 ± 9.8%, respectively). Daily NTE administration for five days also resulted in a similar effect. Further, the vasorelaxant effects and related mechanisms were investigated in the aortas of Sprague Dawley rats. NTE showed the dose-dependent blood-vessel-relaxing effect, and its mechanism involves the NO-sGC-cGMP pathway, activation of K⁺ channels, and reduction in the vasoconstrictive action of angiotensin II. Therefore, our study provides basic data indicating the potential use of NTE as a functional food for high blood pressure.

Keywords: NO/cGMP pathway; Rhus chinensis; angiotensin II; blood pressure; endothelium; hypertension; hypotensive effect; nutgall tree; vasorelaxant.

Figure 1

Systolic blood pressure (SBP) and diastolic blood pressure (DBP) values and percent changes via oral administration of 50% ethanolic extract of nutgall tree leaf (NTE) in spontaneously hypertensive rats (SHRs). (A) SBP, (B) DBP, (C) percent changes in SBP, (D) percent changes in DBP. Symbols and vertical lines indicate means ± SEM (n = 6). * p < 0.05, ** p < 0.01 vs. control.

Figure 2

Systolic blood pressure (SBP) and diastolic blood pressure (DBP) values and percent changes via oral administration (1000 mg/kg) of 50% ethanolic extract of nutgall tree leaf (NTE) in spontaneously hypertensive rats (SHRs) for 5 days. (A) SBP, (B) DBP, (C) percent changes in SBP, (D) percent changes in DBP. Symbols and vertical lines indicate means ± SEM (n = 4). * p < 0.05, ** p < 0.01, *** p < 0.001 vs. control.

Figure 3

Vascular relaxation by 50% ethanolic extract of nutgall tree leaf (NTE) on aortic rings contracted with phenylephrine (PE, 1 μM). (A) Cumulative contraction curves and (B) representative traces. Symbols and vertical lines indicate means ± SEM (n = 5). *** p < 0.001 vs. control.

Figure 4

Vascular relaxation by 50% ethanolic extract of nutgall tree leaf (NTE) on aortic rings pre-constricted with phenylephrine (PE, 1 μM) depending on the presence of endothelium. (A) Cumulative contraction curves and (B) representative traces. Symbols and vertical lines indicate means ± SEM (n = 5). *** p < 0.001 vs. [Endothelium (+)].

Figure 5

Effects of N^G-nitro-L-arginine methyl ester (L-NAME, 100 μM) or indomethacin (10 μM) pretreatment on 50% ethanolic extract of nutgall tree leaf (NTE)-induced vasorelaxation. (A) Cumulative contraction curves and (B) representative traces. Symbols and vertical lines indicate means ± SEM (n = 4–5). *** p < 0.001 vs. control.

Figure 6

Effects of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 μM) or methylene blue (MB, 10 μM) pretreatment on 50% ethanolic extract of nutgall tree leaf (NTE)-induced vasorelaxation. (A) Cumulative contraction curves and (B) representative traces. Symbols and vertical lines indicate means ± SEM (n = 4–5). *** p < 0.001 vs. control.

Figure 7

Effects of tetraethylammonium (TEA, 1 mM), 4-aminopyridine (4-AP, 1 mM), glibenclamide (10 μM), or barium chloride (BaCl₂, 10 μM) pretreatment on 50% ethanolic extract of nutgall tree leaf (NTE)-induced vasorelaxation. (A) Cumulative contraction curves and (B) representative traces. Symbols and vertical lines indicate means ± SEM (n = 4–5). *** p < 0.001 vs. control.

Figure 8

Inhibitory effect of 50% ethanolic extract of nutgall tree leaf (NTE) on vasoconstrictive action induced by CaCl₂. (A) Changes in vascular tone via Ca²⁺-induced vasoconstriction and (B) representative traces. Symbols and vertical lines indicate means ± SEM (n = 5).

Figure 9

Inhibitory effect of 50% ethanolic extract of nutgall tree leaf (NTE) on vasoconstrictive action induced by angiotensin II (Ang II). (A) Changes in vascular tone via Ang II-induced vasoconstriction and (B) representative traces. Symbols and vertical lines indicate means ± SEM (n = 4–5). *** p < 0.001 vs. control.