Rotoli Bianca Maria, Visigalli Rossana, Ferrari Francesca, Ranieri Marianna, Tamma Grazia, Dall'Asta Valeria, Barilli Amelia
Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy.
Department of Bioscience, Biotechnology and Biopharmaceutics, University of Bari, 70125 Bari, Italy.
Biomolecules. 2022 Mar 2;12(3):389. doi: 10.3390/biom12030389.
Desmopressin (dDAVP) is the best characterized analogue of vasopressin, the endocrine regulator of water balance endowed with potent vasoconstrictive effects. Despite the use of dDAVP in clinical practice, ranging from the treatment of nephrogenic diabetes insipidus to bleeding disorders, much remains to be understood about the impact of the drug on endothelial phenotype. The aim of this study was, thus, to evaluate the effects of desmopressin on the viability and function of human pulmonary microvascular endothelial cells (HLMVECs). The results obtained demonstrate that the vasopressor had no cytotoxic effect on the endothelium; similarly, no sign of endothelial activation was induced by dDAVP, indicated by the lack of effect on the expression of inflammatory cytokines and adhesion molecules. Conversely, the drug significantly stimulated the production of nitric oxide (NO) and the expression of the inducible isoform of nitric oxide synthase, NOS2/iNOS. Since the intracellular level of cAMP also increased, we can hypothesize that NO release is consequent to the activation of the vasopressin receptor 2 (V2R)/guanylate cyclase (Gs)/cAMP axis. Given the multifaceted role of NOS2-deriving NO for many physio-pathological conditions, the meanings of these findings in HLMVECs appears intriguing and deserves to be further addressed.
去氨加压素（dDAVP）是血管加压素特征最明确的类似物，血管加压素是一种具有强大血管收缩作用的水平衡内分泌调节因子。尽管dDAVP在临床实践中有广泛应用，从治疗肾性尿崩症到出血性疾病，但关于该药物对内皮细胞表型的影响仍有许多有待了解之处。因此，本研究的目的是评估去氨加压素对人肺微血管内皮细胞（HLMVECs）活力和功能的影响。所获得的结果表明，这种血管加压素对内皮细胞没有细胞毒性作用；同样，dDAVP也未诱导内皮细胞活化迹象，这表现为对炎性细胞因子和黏附分子表达没有影响。相反，该药物显著刺激了一氧化氮（NO）的产生以及一氧化氮合酶诱导型异构体NOS2/iNOS的表达。由于细胞内cAMP水平也升高，我们可以推测NO的释放是血管加压素受体2（V2R）/鸟苷酸环化酶（Gs）/cAMP轴激活的结果。鉴于NOS2衍生的NO在许多生理病理状况中具有多方面作用，这些在HLMVECs中的发现的意义显得很有趣，值得进一步探讨。
