Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, PE, Brazil.
Eur J Pharm Sci. 2013 Mar 12;48(4-5):709-16. doi: 10.1016/j.ejps.2012.12.033. Epub 2013 Jan 10.
The present study investigated the mechanisms underlying the vasorelaxant effects of the essential oil of Aniba canelilla (EOAC) and its main constituent 1-nitro-2-phenylethane (NP) in isolated superior mesenteric artery from spontaneously hypertensive rats (SHRs). At 0.1-1000 μg/mL, EOAC and NP relaxed SMA preparations pre-contracted with 75 mMKCl with IC(50) (geometric mean [95% confidence interval]) values of 294.19 [158.20-94.64] and 501.27 [378.60-624.00] μg/mL, respectively); or with phenylephrine (PHE) (IC(50)s=11.07 [6.40-15.68] and 7.91 [4.08-11.74) μg/mL, respectively). All these effects were reversible and remained unaltered by vascular endothelium removal. In preparations maintained under Ca(2+)-free conditions, EOAC and NP (both at 600 μg/mL) reduced the PHE-, but not the caffeine-induced contraction. In Ca(2+)-free and high K(+) (75 mM) medium, the contractions produced by CaCl(2) or BaCl(2) were reduced or even abolished by EOAC and NP at 100 and 600 μg/mL, respectively. EOAC and NP (both at 10-1000 μg/mL) also relaxed the contraction evoked by phorbol dibutyrate (IC(50)=52.66 [10.82-94.64] and 39.13 [31.55-46.72] μg/mL, respectively). It is concluded that NP has a myogenic endothelium-independent vasorelaxant effects and appears to be the active principle of the EOAC. Vasorelaxant effect induced by both EOAC and NP is preferential to receptor-activated pathways and it appears to occur intracellularly more than a superficial action restricted to the membrane environment such as a simple blocking activity on a given receptor or ion channel.
本研究旨在探讨香桃木油(EOAC)及其主要成分 1-硝基-2-苯乙烷(NP)在自发性高血压大鼠(SHR)离体肠系膜上动脉中的血管舒张作用机制。在 0.1-1000μg/mL 浓度下,EOAC 和 NP 分别以 294.19[158.20-94.64]和 501.27[378.60-624.00]μg/mL 的 IC50 值舒张预收缩于 75mM KCl 的 SMA 标本;或预收缩于苯肾上腺素(PHE)(IC50 分别为 11.07[6.40-15.68]和 7.91[4.08-11.74]μg/mL)的 SMA 标本。所有这些作用均为可逆的,且不受血管内皮去除的影响。在维持于无钙条件下的标本中,EOAC 和 NP(均为 600μg/mL)降低 PHE 引起的收缩,但不降低咖啡因引起的收缩。在无钙和高钾(75mM)介质中,100 和 600μg/mL 的 EOAC 和 NP 分别降低或甚至消除由 CaCl2 或 BaCl2 引起的收缩。EOAC 和 NP(均为 10-1000μg/mL)也舒张佛波醇二丁酸(PDBu)引起的收缩(IC50 分别为 52.66[10.82-94.64]和 39.13[31.55-46.72]μg/mL)。综上所述,NP 具有肌源性内皮非依赖性血管舒张作用,似乎是 EOAC 的活性成分。EOAC 和 NP 引起的血管舒张作用优先于受体激活途径,似乎发生在细胞内,而不是仅限于膜环境的浅表作用,例如对特定受体或离子通道的简单阻断作用。