Antihypertensive Effects of Lindera erythrocarpa Makino via NO/cGMP Pathway and Ca2+ and K+ Channels

Abstract

Studies have demonstrated the therapeutic effects of Lindera plants. This study was undertaken to reveal the antihypertensive properties of Lindera erythrocarpa leaf ethanolic extract (LEL). Aorta segments of Sprague-Dawley rats were used to study the vasodilatory effect of LEL, and the mechanisms involved were evaluated by treating specific inhibitors or activators that affect the contractility of blood vessels. Our results revealed that LEL promotes a vasorelaxant effect through the nitric oxide/cyclic guanosine 3',5'-monophosphate pathway, blocking the Ca²⁺ channels, opening the K⁺ channels, and inhibiting the vasoconstrictive action of angiotensin II. In addition, the effects of LEL on blood pressure were investigated in spontaneously hypertensive rats by the tail-cuff method. LEL (300 or 1000 mg/kg) was orally administered to the rats, and 1000 mg/kg of LEL significantly lowered the blood pressure. Systolic blood pressure decreased by -20.06 ± 4.87%, and diastolic blood pressure also lowered by -30.58 ± 5.92% at 4 h in the 1000 mg/kg LEL group. Overall, our results suggest that LEL may be useful to treat hypertensive diseases, considering its vasorelaxing and hypotensive effects.

Keywords: Lindera erythrocarpa; NO/cGMP pathway; angiotensin II; blood pressure; endothelium; hypertension; hypotensive effect; spontaneously hypertensive rat; vasorelaxant.

Figure 1

Effect of Lindera erythrocarpa leaf 50% ethanol extract (LEL) on endothelium-intact [E(+)] or endothelium-absent [E(−)] aorta, which underwent induced constriction with phenylephrine (PE, 1 μM). To confirm the endothelium, relaxation of pre-constricted aortas was induced by acetylcholine (ACh, 10 μM). (A,C) Relaxation response to LEL and (B,D) representative tracing. Data shown are the mean ± standard error of the mean (SEM) (n = 5). * p < 0.05, ** p < 0.01, *** p < 0.001 vs. control.

Figure 2

Effect of LEL on aortic rings which underwent induced constriction by PE (1 μM) without (Control) or with the incubation of L-NAME (100 μM) or indomethacin (10 μM). (A) Relaxation response to LEL and (B) representative tracing. Data shown are the mean ± SEM (n = 5–6). *** p < 0.001 vs. control.

Figure 3

Effect of LEL on aortic rings with induced contraction by PE (1 μM), without (Control) or with the incubation of ODQ (10 μM) or MB (10 μM). (A) Relaxation response to LEL and (B) representative tracing. Data shown are the mean ± SEM (n = 5–6). *** p < 0.001 vs. control.

Figure 4

Effect of LEL on Ca²⁺ influx in the thoracic aorta. The rings were treated with PE (1 μM) before the constriction caused by CaCl₂. (A) Contraction response to CaCl₂ and (B) representative tracing. Data shown are the mean ± SEM (n = 4–6). *** p < 0.001 vs. control.

Figure 5

Effect of LEL on Ca²⁺ influx via L-type Ca²⁺ channel. LEL were applied to the rings (1000 µg/mL) before inducing contractions using Bay K8644 (10 µM). (A) Contraction response by Bay K8644 and (B) representative tracing. Data are presented as mean ± SEM (n = 5). *** p < 0.001 vs. control.

Figure 6

Effect of LEL on aortic rings with induced contraction by PE (1 μM) without (Control) or with the incubation of BaCl₂ (10 μM), 4-AP (1 mM), or TEA (1 mM). (A) Relaxation response to LEL and (B) representative tracing. Data shown are the mean ± SEM (n =5–6). *** p < 0.001 vs. control.

Figure 7

Effect of LEL on rings constricted by angiotensin II. (A) Contraction response to angiotensin II and (B) representative tracing. Data shown are the mean ± SEM (n = 4–5). * p < 0.05 vs. control.

Figure 8

The effect of LEL on blood pressure. (A) SBP, (B) DBP, (C) MBP, (D) percent changes in SBP, (E) percent changes in DBP and (F) percent changes in MBP. Data shown are the mean ± SEM (n = 5). ** p < 0.01 vs. control.