Desmopressin Stimulates Nitric Oxide Production in Human Lung Microvascular Endothelial Cells

Abstract

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.

Perioperative water and electrolyte balance and water homeostasis regulation in children with acute surgery

“…31,32 Even more importantly, studies conducted in animals have shown that nitric oxide modulates water and electrolyte handling along nephron partly via non-cGMPdependent mechanisms, 34 and decreases AVP-stimulated water and sodium reabsorption in the collecting duct. 35 It is also noteworthy to mention that in rats exposed to a continuous intravascular infusion of l-deamino-8-arginine-vasopressin, 36 which may increase nitric oxide formation, 37 plasma volume expansion was accompanied by a progressive increase in urine flow and decreases in urine osmolality and free water reabsorption despite the presence of AVP, 36 a phenomenon known as renal "escape". 38,39 Taken together, these data suggest that the process of escape from AVP-induced antidiuresis might have occurred in our patients.…”

Cytokine-Induced iNOS in A549 Alveolar Epithelial Cells: A Potential Role in COVID-19 Lung Pathology

“…The production of nitric oxide (NO) was determined by means of a fluorimetric approach, addressing the production of the fluorescent molecule 1-(H)-naphtotriazole from 2,3-diaminonaphthalene (DAN) in an acid environment, as previously described [32]. In total, 100 µL of the cell medium was mixed with 20 µL of DAN (0.025 mg/mL in 0.31 M HCl).…”