Testai L, D'Antongiovanni V, Piano I, Martelli A, Citi V, Duranti E, Virdis A, Blandizzi C, Gargini C, Breschi M C, Calderone V
Department of Pharmacy, University of Pisa, Via Bonanno, 6. I-56126 Pisa, Italy.
Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 55. I-56126 Pisa, Italy.
Nitric Oxide. 2015 May 1;47:25-33. doi: 10.1016/j.niox.2015.03.003. Epub 2015 Mar 17.
Hydrogen sulfide (H2S) and nitric oxide (NO) play pivotal roles in the cardiovascular system. Conflicting results have been reported about their cross-talk. This study investigated their interplays in coronary bed of normotensive (NTRs) and spontaneously hypertensive rats (SHRs). The effects of H2S- (NaHS) and NO-donors (sodium nitroprusside, SNP) on coronary flow (CF) were measured in Langendorff-perfused hearts of NTRs and SHRs, in the absence or in the presence of propargylglycine (PAG, inhibitor of H2S biosynthesis), L-NAME (inhibitor of NO biosynthesis), ODQ (inhibitor of guanylate cyclase), L-Cysteine (substrate for H2S biosynthesis) or L-Arginine (substrate for NO biosynthesis). In NTRs, NaHS and SNP increased CF; their effects were particularly evident in Angiotensin II (AngII)-contracted coronary arteries. The dilatory effects of NaHS were abolished by L-NAME and ODQ; conversely, PAG abolished the effects of SNP. In SHRs, high levels of myocardial ROS production were observed. NaHS and SNP did not reduce the oxidative stress, but produced clear increases of the basal CF. In contrast, in AngII-contracted coronary arteries of SHRs, significant hyporeactivity to NaHS and SNP was observed. In SHRs, the vasodilatory effects of NaHS were only modestly affected by L-NAME and ODQ; PAG poorly influenced the effects of SNP. Then, in NTRs, the vascular actions of H2S required NO and vice versa. By contrast, in SHRs, the H2S-induced actions scarcely depend on NO release; as well, the NO effects are largely H2S-independent. These results represent the first step for understanding pathophysiological mechanisms of NO/H2S interplays under both normotensive and hypertensive conditions.
硫化氢（H₂S）和一氧化氮（NO）在心血管系统中发挥着关键作用。关于它们之间的相互作用，已有相互矛盾的研究结果报道。本研究调查了它们在正常血压大鼠（NTRs）和自发性高血压大鼠（SHRs）冠状动脉床中的相互作用。在NTRs和SHRs的Langendorff灌注心脏中，在不存在或存在炔丙基甘氨酸（PAG，H₂S生物合成抑制剂）、L - 硝基精氨酸甲酯（L - NAME，NO生物合成抑制剂）、1H - [1,2,4]恶二唑[4,3 - a]喹嗪 - 1 - 酮（ODQ，鸟苷酸环化酶抑制剂）、L - 半胱氨酸（H₂S生物合成底物）或L - 精氨酸（NO生物合成底物）的情况下，测量了H₂S供体（硫氢化钠，NaHS）和NO供体（硝普钠，SNP）对冠状动脉血流量（CF）的影响。在NTRs中，NaHS和SNP增加了CF；它们的作用在血管紧张素II（AngII）收缩的冠状动脉中尤为明显。L - NAME和ODQ消除了NaHS的舒张作用；相反，PAG消除了SNP的作用。在SHRs中，观察到心肌活性氧生成水平较高。NaHS和SNP并未降低氧化应激，但使基础CF明显增加。相反，在SHRs的AngII收缩冠状动脉中，观察到对NaHS和SNP的显著反应性降低。在SHRs中，NaHS的血管舒张作用仅受到L - NAME和ODQ的适度影响；PAG对SNP作用的影响较小。然后，在NTRs中，H₂S的血管作用需要NO，反之亦然。相比之下，在SHRs中，H₂S诱导的作用几乎不依赖于NO释放；同样，NO的作用在很大程度上也不依赖于H₂S。这些结果是理解正常血压和高血压条件下NO/H₂S相互作用病理生理机制的第一步。
