Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Dubravska Cesta 9, 845 05 Bratislava, Slovakia.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, 832 32 Bratislava, Slovakia.
Int J Mol Sci. 2020 Sep 12;21(18):6685. doi: 10.3390/ijms21186685.
We characterized modes of action of NO-donor S-nitrosoglutathione (GSNO) and NO-synthase inhibitor l-NAME derived from dicrotic (DiN) and anacrotic (AnN) notches of rat arterial pulse waveform (APW) in the condition of increased/decreased NO bioavailability. The cross-relationship patterns of DiN and AnN with 34 hemodynamic parameters (HPs) induced by GSNO and l-NAME are presented. After GSNO bolus administration, approximate non-hysteresis relationships were observed in the difference between DiN-AnN (mmHg) blood pressure (BP) and other 19 HPs, suggesting that these HPs, i.e., their signaling pathways, responding to NO concentration, are directly connected. Hysteresis relationships were observed between DiN-AnN (mmHg) and other 14 HPs, suggesting that signaling pathways of these HPs are indirectly connected. The hysteresis relationships were only observed between the time interval DiN-AnN (ms) and other 34 HPs, indicating no direct connection of signaling pathways. The cross-relationship patterns of DiN-AnN (mmHg), but not DiN-AnN (ms), induced by l-NAME were in accordance to the increased NO bioavailability induced by GSNO. In conclusion, we found the non-hysteresis/hysteresis cross-relationship "patterns" of DiN-AnN intervals to other HPs in the presence of GSNO that revealed their direct or indirect signaling pathways connections. This may contribute to our understanding of biological effects of natural substances that modulate NO production and/or NO signaling pathways.
我们描述了一氧化氮供体 S-亚硝基谷胱甘肽（GSNO）和一氧化氮合酶抑制剂 l-NAME 的作用模式，这些模式来源于大鼠动脉脉搏波形（APW）的双峰（DiN）和单峰（AnN）切迹，在增加/减少 NO 生物利用度的情况下。本文呈现了 GSNO 和 l-NAME 诱导的 34 个血流动力学参数（HPs）与 DiN 和 AnN 的交叉关系模式。在 GSNO 推注给药后，在 DiN-AnN（mmHg）血压（BP）与其他 19 个 HPs 的差值中观察到近似无滞后关系，表明这些 HPs 及其对 NO 浓度做出反应的信号通路是直接相连的。在 DiN-AnN（mmHg）与其他 14 个 HPs 之间观察到滞后关系，表明这些 HPs 的信号通路是间接相连的。滞后关系仅在 DiN-AnN（ms）时间间隔与其他 34 个 HPs 之间观察到，表明信号通路之间没有直接连接。由 l-NAME 诱导的 DiN-AnN（mmHg）而不是 DiN-AnN（ms）的交叉关系模式与 GSNO 诱导的增加的 NO 生物利用度相符。总之，我们发现了在 GSNO 存在下，DiN-AnN 间隔与其他 HPs 的非滞后/滞后交叉关系“模式”，揭示了它们的直接或间接信号通路连接。这可能有助于我们理解调节 NO 产生和/或 NO 信号通路的天然物质的生物学效应。
