Huerta de la Cruz Saúl, Medina-Terol Grecia J, Sánchez-López Araceli, Centurión David
Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Del. Tlalpan, C.P. 14330 México D.F., Mexico.
Peptides. 2022 Nov;157:170861. doi: 10.1016/j.peptides.2022.170861. Epub 2022 Aug 13.
Hydrogen sulfide (HS) is a gasotransmitter that modulates the peripheral transmission regulating the vascular tone. In vitro studies have suggested that HS induces vasodilation by stimulating capsaicin-sensitive sensory neurons. This study was designed to determine the effects of HS on the non-adrenergic/non-cholinergic (NANC) outflow in the pithed rat, and the underlying mechanisms. For that purpose, 72 male Wistar rats were anesthetized, pithed and the carotid, femoral and jugular veins were cannulated and then divided into two main sets. The first set of animals (n = 48) was used to determine the effect of NaHS (HS donor) on the vasodepressor responses induced by: 1) NANC outflow electrical stimulation (n = 24); and 2) i.v. bolus of α-CGRP (n = 24) and subdivided into 4 groups (n = 6 each): 1) control group (without infusion); continuous infusion of: 2) PBS (vehicle; 0.02 ml/kg·min); 3) NaHS 10 μg/kg·min; and 4) NaHS 18 μg/kg·min. The second set of animals (n = 24) received an i.v. bolus of either (1) HC 030031 (TRPA1 channel antagonist; 18 μg/kg; n = 12) or (2) capsazepine (TRPV1 channel antagonist; 100 μg/kg; n = 12) in presence and absence of 18 µg/kg·min NaHS i.v. continuous infusion to determine the underlying mechanism of the NaHS effect on the NANC outflow. Our results show that NaHS infusion increased the vasodepressor responses induced by electrical stimulation, but not by α-CGRP, effect that was abolished by HC030031 and remained unaffected after capsazepine. These data suggest that activation of TRPA1 channels, but no TRPV1, is responsible for the NaHS-induced NANC neurotransmission stimulation.
硫化氢（HS）是一种气体递质，可调节外周传导，调控血管张力。体外研究表明，HS通过刺激辣椒素敏感的感觉神经元诱导血管舒张。本研究旨在确定HS对脊髓毁损大鼠非肾上腺素能/非胆碱能（NANC）传出神经的影响及其潜在机制。为此，将72只雄性Wistar大鼠麻醉、脊髓毁损，然后将颈静脉、股静脉和颈动脉插管，再分为两组。第一组动物（n = 48）用于确定硫氢化钠（NaHS，HS供体）对以下因素诱导的血管减压反应的影响：1）NANC传出神经电刺激（n = 24）；2）静脉注射α - 降钙素基因相关肽（α - CGRP，n = 24），并再细分为4组（每组n = 6）：1）对照组（无输注）；持续输注：2）磷酸盐缓冲液（PBS，溶剂；0.02 ml/kg·min）；3）10 μg/kg·min的NaHS；4）18 μg/kg·min的NaHS。第二组动物（n = 24）静脉注射以下物质之一：（1）HC 030031（TRPA1通道拮抗剂；18 μg/kg；n = 12）或（2）辣椒平（TRPV1通道拮抗剂；100 μg/kg；n = 12），同时存在或不存在18 μg/kg·min的NaHS静脉持续输注，以确定NaHS对NANC传出神经作用的潜在机制。我们的结果表明，输注NaHS可增强电刺激诱导的血管减压反应，但对α - CGRP诱导的反应无影响，HC030031可消除该效应，而辣椒平对此无影响。这些数据表明，TRPA1通道而非TRPV1通道的激活介导了NaHS诱导的NANC神经传递刺激。
