Desmopressin Stimulates Nitric Oxide Production in Human Lung Microvascular Endothelial Cells.

Bianca Maria Rotoli,Amelia Barilli,Valeria Dall’Asta,Francesca Ferrari,Rossana Visigalli,Marianna Ranieri,Grazia Tamma

doi:10.3390/biom12030389

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.

Highlights

Desmopressin (1-deamino-8-D-arginin vasopressin; deamino-8-D-arginine vasopressin (dDAVP)) is a synthetic analogue of vasopressin (AVP)
Intracellular calcium sible for the regulation of NOS2 expression in many cell types [29], this finding further were in cells in treated for the indicated times at times steady-state and calibrated as described in levelsmeasured were measured cells treated for the indicated at steady-state and calibrated as desupports a role for the inducible isoform of the enzyme in the desmopressin-mediated scribed inand
Despite the large use in the clinical practice, little is still known about the impact of the

Summary

Introduction

Desmopressin (1-deamino-8-D-arginin vasopressin; dDAVP) is a synthetic analogue of vasopressin (AVP). The latter, called an “antidiuretic hormone” (ADH), is a natural hormone with potent vasoconstrictive effects and the key endocrine regulator of water balance [1]. The activity of AVP and its analogues depends on the binding to specific receptors on the cell surface, such as AVPR1A/V1aR, AVPR2/V2R, and AVPR1B/V1bR. V1aR is mainly expressed on smooth muscle cells where its activation increases intracellular Ca2+ content via phosphatidyl-inositol intracellular cascade, leading to vasoconstriction.

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