夏枯草醇提取物对正常大鼠离体胸主动脉环的舒张作用

目的：探讨夏枯草醇提取物对胸主动脉环的舒张作用及其作用机制。方法：采用大鼠离体胸主动脉环灌流模型法,观察夏枯草醇提取物（0.05,0.10和0.15mg.ml-1）对苯肾上腺素（PE）1.0μmol.L-1和KCl 50 mmol.L-1预收缩的胸主动脉环张力的影响。结果：夏枯草醇提取物对离体大鼠内皮完整和去内皮的胸主动脉环均有浓度依赖性的舒张作用,而对苯肾上腺素（PE）预收缩血管的舒张作用是内皮依赖性的。用一氧化氮合酶抑制L-NAME和岛苷酸环化酶抑制剂MB预处理后,两者的血管舒张作用均被阻断。但用环氧合酶抑制剂吲哚美辛,不能阻断夏枯草醇提取物引起的舒张血管作用。结论：夏枯草醇提取物可能是通过NO-鸟苷酸环化酶途径产生内皮依赖性的血管舒张作用。     

山楂水提取物对正常大鼠离体胸主动脉环的舒张作用及其机制

目的：探讨山楂水提取物对胸主动脉环的舒张作用及其作用机制。方法：采用累积加药法,检测山楂水提取物（0．1,0．3和0．5mg／m1）对苯肾上腺素（PE）1．0μmol．L^-1和KCl50mmol．L^-1预收缩的胸主动脉环张力的影响。结果：山植水提取物对离体大鼠内皮完整和去内皮的胸主动脉环均有浓度依赖性的舒张作用,而对苯肾上腺素（PE）预收缩血管的舒张作用是内皮依赖性的。用一氧化氮合酶抑制剂L-NAME和鸟苷酸环化酶抑制剂MB预处理后,两者的血管舒张作用均被阻断。但用环氧合酶抑制剂吲哚关辛,不能阻断山楂引起的舒张血管作用。结论：山楂水提取物可能是通过NO-鸟苷酸环化酶途径产生内皮依赖性的血管舒张作用。     

杜鹃素对大鼠离体主动脉的舒张作用及机制

目的探讨杜鹃素（DJS）对大鼠离体主动脉的舒张作用与机制。方法制备SD大鼠离体主动脉环。采用离体血管环实验方法,通过生物信号采集与分析系统测定血管环的变化。结果杜鹃素能够浓度依赖性地舒张大鼠离体主动脉环,对KCl预收缩的内皮完整的血管环最大舒张幅度明显强于对去除内皮血管环的舒张作用;预孵一氧化氮合酶抑制剂L-NAME后,DJS对内皮完整的血管环的最大舒张幅度明显降低（P〈0.05或P〈0.001）。结论 DJS能够浓度依赖性舒张大鼠离体主动脉,其作用机制可能与血管内皮细胞促进一氧化氮的释放有关。     

培哚普利对大鼠胸主动脉的舒张机制研究

目的观察培哚普利对大鼠离体胸主动脉张力的影响,并探讨其舒张作用机制。方法采用离体血管张力实验方法,观察培哚普利在1×10^-9mol／L,1×10^-8mol／L,1×10^-7mol／L,1×10^-6mol／L,1×10^-5mol／L,1×10^-4mol／L浓度时,对去甲肾上腺素（NE,1×10^-6mol／L）诱发大鼠离体胸主动脉环收缩的影响。观察内皮、一氧化氮合酶（eNOS）抑制剂N-硝基-L-精氨酸甲酯（L—NAME,10^-4mol／L）、环氧合酶抑制剂吲哚美辛（indometacin,10mol／L）、乌苷酸环化酶抑制剂亚甲蓝（MB,10^-6mol／L）对培哚普利舒血管作用的影响。结果培哚普利对NE（1×10^-6 m0l／L）预收缩的大鼠离体胸主动脉环产生浓度依赖性的舒张作用。去内皮、L—NAME、Indo及MB可显著减弱培哚普利对血管环的舒张作用（P〈0．05或P〈0．01）。结论培哚普利对NE预收缩的大鼠胸主动脉环具有浓度依赖性的舒张作用,其舒张反应有内皮依赖性,可能与内皮产生的一氧化氮（NO）及前列环素（PGI2）的合成有关,可能通过NO-鸟苷酸环化酶（sGC）途径产生内皮依赖性的舒张作用。     

丹参对离体大鼠主动脉环舒张作用的机制

目的研究中药丹参(SM)对离体大鼠胸主动脉环舒缩张力的作用及其可能途径。方法采用大鼠离体胸主动脉灌流技术,以累积浓度法观测SM对基础状态、去甲肾上腺素(10μmol/L)和氯化钾(60 mmol/L)预收缩的血管环张力的影响;运用一氧化氮合酶抑制剂左旋硝基精氨酸甲酯(0.1 mmol/L)、鸟苷酸环化酶抑制剂亚甲蓝(10μmol/L)及环氧合酶抑制剂吲哚美辛(10μmol/L)处理血管环,探讨SM影响血管环张力的机制。结果SM(0.1,0.3,1.0,3.0,10.0 g/L)对基础状态或氯化钾预收缩的血管环无影响,而对去甲肾上腺素预收缩的内皮完整血管环产生浓度依赖性的舒张作用,并且去除内皮后,SM的舒张作用被取消。用左旋硝基精氨酸甲酯和亚甲蓝预处理后,均可阻断SM的舒张血管作用,而用吲哚美辛(10μmol/L)预处理后未能阻断SM的血管舒张作用。结论SM通过一氧化氮-鸟苷酸环化酶途径产生内皮依赖的血管舒张作用。     

替米沙坦对大鼠离体胸主动脉环的舒张作用

目的观察替米沙坦对大鼠离体胸主动脉环张力的影响,并探讨其作用机制。方法采用离体血管张力实验方法。观察替米沙坦在1×10-9mol/L,1×10^-8mol/L,1×10^-7mol/L,1×10^-6mol/L,1×10^-5mol/L浓度时,对去甲肾上腺素（NE,1×10^-6mol/L）诱发大鼠离体胸主动脉环收缩的影响。观察内皮型一氧化氮合酶（eNOS）抑制剂N-硝基-L-精氨酸甲酯（L-NAME,10-4mol/L）、环氧合酶抑制剂吲哚美辛（10^-5mol/L）对替米沙坦作用的影响,以及替米沙坦对血管环外钙依赖性收缩和内钙依赖性收缩的影响。结果替米沙坦对NE（1×10^-6mol/L）预收缩的离体胸主动脉环产生浓度依赖性的舒张作用。用Indo预处理的血管环对替米沙坦的舒张反应与未经处理时比较无统计学意义（P〉0.05）。去内皮及L-NAME可显著减弱替米沙坦对血管环的舒张作用（P〈0.05）。替米沙坦对血管环外钙依赖性收缩和内钙依赖性收缩无影响作用。结论替米沙坦对NE预收缩的大鼠胸主动脉环具有浓度依赖性的舒张作用,其舒张反应可能有内皮依赖性,与内皮产生的NO有关,与前列环素的合成无关,不通过抑制外钙内流和内钙释放发挥舒张作用。     

大蓟水提取物对正常大鼠离体胸主动脉环的舒张作用及其机制

目的：探讨大蓟水提取物对胸主动脉环的舒张作用及其作用机制。方法：采用累积加药法,检澳4大蓟水提取物（0．1,0．3和1．0mg／ml）对苯肾上腺素（PE）1．0umol／L预收缩的胸主动脉环张力的影响。结果：大蓟水提取物对离体大鼠内皮完整的胸主动脉环均有浓度依赖性的舒张作用,并对苯肾上腺素（PE）预收缩血管的舒张作用是内皮依赖性的。用一氧化氮合酶抑制剂L-NAME年口鸟苷酸环化酶抑制剂MB预处理后,两者的血管舒张作用均被阻断。但用环氧舍酶抑制剂吲哚关辛,不能阻断大蓟引起的舒张血管作用。结论：大蓟水提取物可能是通过NO-鸟苷酸环化酶途径产生内皮依赖性的血管舒张作用。     

人参皂甙CompoundK对离体大鼠胸主动脉平滑肌的作用研究

目的：研究人参皂甙compoundK（CK）对大鼠胸主动脉平滑肌作用。方法：使用血管张力测定仪,制备大鼠离体胸主动脉环,置于浴槽内,从有无内皮、一氧化氮合酶（NOS）抑制剂,a受体三个方面研究人参皂甙CK对离体大鼠胸主动脉平滑肌的作用。结果：浓度为1～45μg/ml的人参皂甙Rb1对大鼠胸主动脉平滑肌无明显舒张作用,其代谢产物人参皂甙CK（浓度为3,6,12,24μg/ml）对大鼠离体胸主动脉平滑肌有明显的舒张作用,与空白对照有显著性差异（P〈0.01）,且呈剂量依赖性,浓度为24μg/ml的人参皂甙CK对血管平滑肌的舒张率达到51.1%;去除血管内皮组织或NOS抑制剂L-NNA的存在下,人参皂甙CK的血管舒张作用消失。结论：人参皂甙CK对离体大鼠胸主动脉平滑肌具有内皮依赖性舒张作用。其机制可能与内皮舒张因子有关,其作用机制有待于进一步深入研究。     

三黄泻心汤水提取液对大鼠离体胸主动脉环的舒张作用及机制

目的：研究三黄泻心汤水提取液舒血管作用的可能机制。方法：记录苯肾上腺素（PE）和KCl预收缩的离体大鼠主动脉环张力变化,观察三黄泻心汤水提取液舒血管作用及不同工具药对舒血管作用的影响。结果：三黄泻心汤水提取液（0.1,0.3,0.5mg/ml）对PE（1.0μmol·L^-1）和KCl（50mmol·L^-1）预收缩的大鼠主动脉环均有非内皮依赖的、浓度依赖性的舒张作用。对PE（1.0μmol·L^-1）预收缩的去内皮血管环,三黄泻心汤水提取液（0.5mg/ml）呈舒张作用,分别用一氧化氮合酶抑制剂左旋硝基精氨酸甲酯（L-NAME）（0.1mmol·L^-1）和鸟苷酸环化酶抑制剂亚甲蓝（MB）（10μmol·L^-1）预处理无明显影响。在无钙营养液（含EGTA）环境下,三黄泻心汤预处理对苯肾上腺素（PE）收缩有明显抑制作用。结论：三黄泻心汤有浓度依赖性的血管舒张作用,此作用即不依赖血管内皮,又和内皮源性的舒张因子NO无关,可能与抑制血管平滑肌细胞内质网储存钙的释放有关。     

金丝桃苷对离体大鼠腹主动脉的舒张作用及其机制研究

目的研究金丝桃苷对离体大鼠腹主动脉环的舒张作用并探讨其可能的作用机制。方法在大鼠离体腹主动脉环上,分别观察累积浓度的金丝桃苷(1×10-6.5~1×10-4mol/L)对KCl(30mmol/L)和U46619(血栓素类似物,1×10-7mol/L)预收缩血管环的作用。结果金丝桃苷能够浓度依赖性舒张由KC1和U46619预收缩的血管环,最大舒张率分别为(52.2±7.2)%、(80.7±4.1)%;去除血管内皮后,最大舒张率分别降为(15.4±1.2)%、(21.6±1.2)%,与内皮完整组比较有显著差异(P0.01)。在30mmol/L KCl和1×10-7mol/L U46619预收缩的内皮完整血管环,用一氧化氮(NO)合酶抑制剂(L-NAME,3×10-4mol/L)预温育后,金丝桃苷的最大舒张率分别降为(23.0±3.0)%、(40.3±3.6)%,与未加L-NAME组比较有显著差异(P0.01);用环氧酶抑制剂吲哚美辛(1×10-5mol/L)预温育对金丝桃苷的舒张血管作用没有明显的影响;在U46619预收缩的血管环,合用L-NAME和吲哚美辛不能完全阻断金丝桃苷引起的血管舒张,最大舒张率为(36.6±1.9)%,与去内皮组比较差异显著(P0.01)。结论金丝桃苷具有内皮依赖性和较弱的非内皮依赖性血管舒张作用,其内皮依赖性血管舒张可能涉及到内皮NO和内皮依赖性超极化因子(endothelium-derived hyperpolarizing factor,EDHF)的释放。     

The Lignan (‐)‐Cubebin Inhibits Vascular Contraction and Induces Relaxation Via Nitric Oxide Activation in Isolated Rat Aorta

Cubebin, the most abundant lignan in Piper cubeba, has been described as having several effects as trypanocidal, antimycobacterial, antispasmodic, antimicrobial, anti‐inflammatory, and analgesic. This study investigated the vasorelaxant effect produced by (‐)‐cubebin in isolated rat aortic rings pre‐contracted with phenylephrine (Phe), and the possible mechanism involved in this event was evaluated. Endothelium‐dependent relaxation was evoked by acetylcholine and (‐)‐cubebin in intact aortic rings, while endothelium‐independent vasorelaxation was elicited by sodium nitroprusside and (‐)‐cubebin in denuded rings. Cumulative concentration–response curves for Phe (10^?10–10^?5 M) were determined for endothelium‐intact and endothelium‐denuded aortic rings in either the presence or absence of (‐)‐cubebin. Dose–response curves were also constructed for pre‐incubation of vascular rings with Nω‐nitro‐L‐arginine methyl ester (L‐NAME) (a non‐specific nitric oxide synthase inhibitor), indomethacin (an unspecific cyclooxygenase inhibitor), and 1H‐[1,2,4] oxadiazolo [4,3‐a]quinoxalin‐1‐one (ODQ) (a guanylyl cyclase inhibitor). (‐)‐Cubebin was found to exert a vasorelaxant effect irrespective of the presence of endothelium, which was abolished by pretreatment with L‐NAME and ODQ, but not with indomethacin. In addition, (‐)‐cubebin was able to reduce Phe contraction in the case of intact rings. These results suggest that (‐)‐cubebin promotes vasorelaxation via NO/cGMP pathway in rat aorta, without prostacyclin involvement. Copyright © 2013 John Wiley & Sons, Ltd.     

补肾活血浸膏的舒张血管作用及其机理研究

目的:通过观察补肾活血浸膏对豚鼠肠系膜微血管、大鼠胸主动脉环、门静脉环及其血浆的NO、血管的NO和NOS、cNOS、iNOS的影响,研究本方的舒张血管作用及其效应机制.方法:去甲肾上腺素致豚鼠肠系膜微血管收缩研究其整体的舒张血管作用;观察药物对苯肾上腺素收缩离体大鼠胸腔主动脉环或静脉环的作用,以及在预加优降糖或普萘洛尔或去血管内皮后其作用的影响;硝酸还原酶法测定给予药物后大鼠血浆和血管的NO及血管NOS、cNOS、iNSO的含量变化.结果:补肾活血浸膏有扩张去甲肾上腺素致豚鼠肠系膜微血管收缩的作用;松弛苯肾上腺素引起的离体大鼠胸腔主动脉环或静脉环的收缩作用,预加优降糖仍然有松弛作用.然而对预加普萘洛尔后补肾活血浸膏剂量低时保持舒张血管作用,剂量增加时反而引起收缩血管作用,大鼠胸腔主动脉环去内皮后药物无松弛作用,反而引起收缩作用;补肾活血浸膏高、低剂量组均能升高血浆NO水平,但只有高剂量组有显著性差异(P＜0.01);高、低剂量组均能显著性升高大鼠主动脉NO(P＜0.001,P＜0.05);高剂量组显著性升高NOS(P＜0.05)和cNOS(P＜0.001),低剂量组有升高NOS作用,但无显著性差异,对cNOS有显著性升高作用.结论:补肾活血浸膏的舒张血管作用机制与血管内皮释放NO和促进NOS、cNOS合成有关.     

Vascular effects and antioxidant activity of two Combretum species from Democratic Republic of Congo

Ethnopharmacological relevance

Combretum racemosum P. Beauv (Combretaceae) leaves (CrLv) and root bark (CrRB) and Combretum celastroides subsp. laxiflorum Welw (Combretaceae) leaves (ClLv) are used in Congolese traditional medicine for several therapeutic purposes, notably for the treatment of conditions consistent with hypertension. The present study aims to investigate the vasorelaxant and in vitro antioxidant activities of these plants polar extracts and to examine the in vivo antihypertensive effect of the extract which displays the most potent vasorelaxant effect.

Material and methods

The vasorelaxant effect of CrLv, CrRB and ClLv methanolic extracts was studied on rat aorta rings pre-contracted with phenylephrine (PE, 1 μM) in the presence or absence of the endothelium. In some experiments, prior to the addition of the extract, rings were incubated for 30 min with either L-N^G-nitroarginine methyl ester (L-NAME; 100 μM), a nitric oxide synthase (NOS) inhibitor, indomethacin (10 μM), a cyclooxygenase inhibitor, or 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 μM), a guanylate cyclase inhibitor. The antioxidant activity was determined by the measurement of the scavenging ability of extracts towards the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). Blood pressure was measured on normotensive Wistar rats and spontaneously hypertensive rats (SHR) treated orally with a daily dose (40 mg/kg) of the CILv extract for 5 weeks. Tested extracts have been characterised by TLC profiles targeted at flavonoids.

Results

All tested extracts showed an important DPPH scavenging activity, ranging from 0.6 to 1.1 quercetin-equivalents. They caused a concentration-dependent vasorelaxation on intact aortic rings pre-contracted with PE (1 μM). The responses to CrRB and CrLv methanolic extracts reached 74.0±5.1% and 62.2±8.6% at a cumulative concentration of 50 μg/ml, respectively. The ClLv (10 μg/ml) extract was more active and, in the same conditions, relaxed aortic rings by 90.3±5.8%. The vasorelaxant activity of all extracts disappeared or was significantly attenuated by removal of the endothelium or after pretreatment with L-NAME or ODQ. Indomethacin only inhibited the activity of CrLv and CrRB extracts. The ClLv extract was able to lower the systolic blood pressure in SHR rats by 7% after a 5-week treatment.

Conclusions

The present study shows that methanolic extracts from ClLv, CrRB and CrLv have an antioxidant activity and an endothelium-dependent vasorelaxant effect. ClLv induces the vasorelaxant effect through the NO-cGMP pathway while CrLv and CrRB extracts also act via a prostanoid pathway. ClLv extract demonstrated a modest but significant antihypertensive activity in SHR rats.     

五种中药提取物的血管活性作用实验研究

目的:观察川芎、大蓟、元参、红花和绞股蓝抽提物的血管活性作用。同时研究了绞股蓝的正丁醇、氯仿及水提取物对离体血管的影响。方法:实验是在有内皮和无内皮的离体大鼠主动脉上完成的。离体大鼠主动脉置于浴槽内,各种中药提取物所引起的血管张力改变被测定。结果:除红花外,其他4种中药引起剂量依赖性舒张作用,内皮存在时舒张反应更明显。绞股蓝的正丁醇提取物引起内皮依赖性扩张反应。而氯仿及水提取物无血管活性作用。结论:川芎、大蓟、元参、绞股蓝可引起内皮源舒张因子增加。红花无此作用。     

Ethanol extract of seeds of Oenothera odorata induces vasorelaxation via endothelium-dependent NO-cGMP signaling through activation of Akt-eNOS-sGC pathway

Aim of study

The vasorelaxant effect of ethanol extract of seeds of Oenothera odorata (Onagraceae) (one species of evening primroses) (ESOO) and its mechanisms involved were defined.

Materials and methods

Changes in vascular tension, guanosine 3′,5′-cyclic monophosphate (cGMP) levels, and Akt expression were measured in carotid arterial rings from rats. Seeds of Oenothera odorata were extracted with ethanol (94%) and the extract was filtered, concentrated and stored at −70 °C.

Results

ESOO relaxed endothelium-intact, but not endothelium-denuded, carotid arterial rings in a concentration-dependent manner. Similarly, ESOO increased cGMP levels of the carotid arterial rings. Pretreatment of endothelium-intact arterial rings with L-NAME, an inhibitor of nitric oxide synthase (NOS), or ODQ, an inhibitor of soluble guanylyl cyclase (sGC), blocked the ESOO-induced vasorelaxation and increase in cGMP levels. Nominally Ca²⁺-free but not L-typed Ca²⁺ channel inhibition attenuated the ESOO-induced vasorelaxation. Thapsigargin, Gd³⁺, and 2-aminoethyl diphenylborinate, modulators of store-operated Ca²⁺ entry (SOCE), significantly attenuated the ESOO-induced vasorelaxation and increase in cGMP levels. Further, wortmannin, an inhibitor of Akt, attenuated the ESOO-induced vasorelaxation and increases in cGMP levels and phosphorylated Akt2 expression. K⁺ channel blockade with TEA, 4-aminopyridine, and glibenclamide attenuated the ESOO-induced vascular relaxation.

Conclusion

Taken together, the present study demonstrates that ESOO relaxes vascular smooth muscle via endothelium-dependent NO-cGMP signaling through activation of the Akt-eNOS-sGC pathway.     

原花青素舒张家兔主动脉和降低动脉血压的研究

目的：研究葡萄籽提取物原花青素(procyanidins，PC)舒张家兔离体主动脉和降低其动脉血压的作用及机制。方法：采用家兔离体胸主动脉环灌流模型，将标本分6组：去内皮、内皮完整、吲哚美辛(1×10^-1 mol·L^-1)、普萘洛尔(1×10^-5 mol·L^-1)、左旋硝基精氨酸N^ω-nitro-L-arginine(L-NNA 1×10^-4 mol·L^-1)或甲烯蓝(MB 1×10^-5 mol·L^-1)，分别累积加入1.25，2.5，5.0 mg·L^-1 PC观察血管张力变化；并观察40 mg·L^-1 PC对去甲肾上腺素（NA）(1×10^-8～1×10^-5 mol·L^-1)、KCl(6.3～100 mmol·L^-1)和CaCl₂ (1×10^-5～1×10^-2 mol·L^-1)诱导血管环收缩曲线的影响。另用家兔颈总动脉插管法，经静脉累积注射4.0，8.0，16，32，64，84 mg·kg^-1 PC后观察血压变化。结果：PC能舒张主动脉血管，并有量效依赖性(r=0.63，P<0.001)，去内皮、L-NNA或MB可减弱PC的舒张作用。PC能抑制NA，KCl和CaCl₂的量效收缩反应。PC能降低家兔正常动脉血压并有量效依赖性(r=0.92，P<0.001)。结论：PC舒张血管的作用是通过抑制细胞内Ca²⁺释放和电压依赖性Ca²⁺通道而减少Ca²⁺内流；也与内皮释放的NO有关；PC可降低家兔正常的动脉血压。     

大黄素对血管紧张素Ⅱ诱导血管平滑肌细胞增殖的影响

目的:观察大黄素对血管紧张素Ⅱ(AngⅡ)诱导血管平滑肌细胞(VSMC)增殖的影响及机制。方法:斑贴法培养大鼠主动脉VSMC,AngⅡ刺激VSMC建立细胞增殖模型。采用MTT法检测细胞增殖,观察大黄素(10,20,40,80μmol.L^-1)、亚硝基-精氨酸甲酯(L-NAME,100μmol.L^-1)对AngⅡ诱导VSMC增殖的影响。免疫组化法检测增殖细胞核抗原(PCNA)表达;硝酸还原酶及化学比色法测细胞上清液中一氧化氮(NO)、一氧化氮合酶(NOS)、诱导型一氧化氮合酶(iNOS)水平。半定量逆转录聚合酶链反应(RT-PCR)检测VSMC iNOS mRNA的表达。结果:大黄素在10~80μmol.L^-1呈剂量及时间依赖性抑制VSMC增殖,但可被100μmol.L^-1的L-NAME部分抵消;大黄素能减少PCNA阳性细胞表达,升高NO,NOS,iNOS水平,增加iNOS mRNA的表达。结论:大黄素对AngⅡ诱导的VSMC增殖有抑制作用,抑制VSMC PCNA的表达,上调iNOS基因表达,升高NO水平可能是其发挥作用的机制。     

Water extract of Zanthoxylum piperitum induces vascular relaxation via endothelium-dependent NO-cGMP signaling

Aim of the study

The aim of the present study was to define the effects of extracts of leaves of Zanthoxylum piperitum (ZP) on the vascular tension and its mechanisms responsible in rat thoracic aortic rings.

Materials and methods

Methanol extract of ZP and aqueous fraction of the methanol extract (AZP) were examined for their vascular relaxant effects in isolated phenylephrine-precontracted aortic rings.

Results

Methanol extract of ZP and aqueous fraction of the methanol extract (AZP) induced relaxation of the phenylephrine-precontracted aortic rings in a concentration-dependent manner. Endothelium-denudation abolished the AZP-induced vasorelaxation. Pretreatment of the endothelium-intact aortic rings with N^G-nitro-l-arginine methylester (L-NAME) and 1H-[1,2,4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ) inhibited the AZP-induced vasorelaxation. Inhibition of Ca²⁺ entry via L-type Ca²⁺ channels failed to block the AZP-induced vasorelaxation. Extracellular Ca²⁺ depletion slightly but significantly attenuated the AZP-induced vasorelaxation. Thapsigargin significantly attenuated the AZP-induced vasorelaxation. Further, Gd³⁺ and 2-aminoethyl diphenylborinate (2-APB), inhibitors of store-operated Ca²⁺ entry (SOCE), markedly attenuated the AZP-induced vasorelaxation. Also, wortmannin, an inhibitor of Akt, an upstream signaling molecule of eNOS, attenuated the AZP-induced vasorelaxation. AZP increased cGMP levels of the aortic rings in a concentration-dependent manner and the effect was blocked by L-NAME, ODQ, thapsigargin, Gd³⁺, 2-APB, and wortmannin. K⁺ channel inhibition with glibenclamide and tetraethylammonium, cyclooxygenase inhibition with indomethacin, and adrenergic and muscarinic receptors blockade had no effects on the AZP-induced vasorelaxation.

Conclusion

Taken together, the present study suggests that AZP relaxes vascular smooth muscle via endothelium-dependent activation of NO-cGMP signaling through the Akt- and SOCE-eNOS pathways.