Division of Pharmacology, Cardiff School of Pharmacy & Pharmaceutical Sciences, Cardiff University, King Edward Vll Avenue, Cathays Park, Cardiff, Wales CF10 3NB, UK.
Division of Pharmacology, Cardiff School of Pharmacy & Pharmaceutical Sciences, Cardiff University, King Edward Vll Avenue, Cathays Park, Cardiff, Wales CF10 3NB, UK.
Vascul Pharmacol. 2019 Oct;121:106580. doi: 10.1016/j.vph.2019.106580. Epub 2019 Jul 23.
Acetylcholine (Ach) causes vasodilatation by nitric oxide (NO) release from the vascular endothelium. Vasoconstrictors such as α-adrenoceptor agonists (phenylephrine) or thromboxane TxA mimetics (U46619) also release endothelial NO. Inhibition of nitric oxide synthase (NOS) with N-nitro-L-arginine (L-NAME) potentiates vasoconstriction by phenylephrine and the trace amine, β-phenylethylamine (PEA), indicating underlying opposing vasodilatation. However, the roles of the endothelium and NO in vasodilator and constrictor responses of guinea-pig aorta have not been examined and are the subject of this study. Guinea-pig thoracic aorta rings were set up in aerated Krebs solution (37 °C) and isometric tension recorded. Contractions to phenylephrine were fast onset, rapidly waned and antagonised by prazosin. PEA contractions were slow onset, sustained and not antagonised by prazosin and therefore not α-adrenoceptor-mediated. PEA and phenylephrine contractions were enhanced by L-NAME whether endothelium was present or not. Ach produced only weak relaxation in a small proportion of endothelium intact U46619-constricted aortae, which were abolished by endothelium removal. In uncontracted aortae Ach caused small contractions, which like PEA contractions were potentiated by endothelium removal. α-Adrenoceptor agonists and trace amines release NO from non-endothelial sites causing underlying opposing vasodilatation. The endothelium plays only a minor role in vasodilator and vasoconstrictor responses of guinea-pigs aorta.
乙酰胆碱 (Ach) 通过血管内皮释放一氧化氮 (NO) 引起血管舒张。血管收缩剂，如 α-肾上腺素受体激动剂（苯肾上腺素）或血栓烷 TxA 模拟物（U46619），也会释放内皮 NO。用 N-硝基-L-精氨酸 (L-NAME) 抑制一氧化氮合酶 (NOS) 可增强苯肾上腺素和微量胺 β-苯乙胺 (PEA) 的血管收缩作用，表明存在潜在的相反的血管舒张作用。然而，内皮和 NO 在豚鼠主动脉舒张和收缩反应中的作用尚未被研究，这是本研究的主题。在充氧 Krebs 溶液（37°C）中建立豚鼠胸主动脉环，并记录等长张力。苯肾上腺素引起的收缩具有快速起始、迅速衰减的特点，并被哌唑嗪拮抗。PEA 收缩起始缓慢，持续时间长，不受哌唑嗪拮抗，因此不是 α-肾上腺素受体介导的。无论内皮是否存在，L-NAME 均增强 PEA 和苯肾上腺素的收缩。Ach 仅在一小部分内皮完整的 U46619 收缩的主动脉中产生微弱的舒张作用，内皮去除后该舒张作用被消除。在未收缩的主动脉中，Ach 引起小的收缩，与 PEA 收缩一样，内皮去除后增强。α-肾上腺素受体激动剂和微量胺从非内皮部位释放 NO，导致潜在的相反的血管舒张。内皮在豚鼠主动脉舒张和收缩反应中仅起次要作用。
