Arginine vasopressin receptor 2 activation promotes microvascular permeability in sepsis

Lopez, Ernesto; Fukuda, Seisuke; Módis, Katalin; Fujiwara, Osamu; Enkhtaivan, Baigal; Trujillo-Abarca, Raul; Ihara, Kenji; Lima-Lopez, Francisco; Pérez-Bello, Dannelys; Szabó, Csaba; Prough, Donald S.; Enkhbaatar, Perenlei

doi:10.1016/j.phrs.2020.105272

Cited by 7 publications

(8 citation statements)

References 51 publications

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“…Literature evidences have recently indicated that short-term incubations (1, 3, 6 h) with dDAVP have no cytotoxic effect on human endothelium in vitro [10]. Consistently, we observed here no change in cell viability at any concentration tested at any time, even for longer incubations, excluding both acute and chronic cytotoxic effects.…”

Section: Discussionsupporting

confidence: 91%

“…Literature evidences have recently indicated that short-term incubations (1, 3, 6 h) with dDAVP have no cytotoxic effect on human endothelium in vitro [10]. Consistently,…”

Section: Discussionsupporting

confidence: 63%

“…The most likely hypothesis is, hence, that whether the induction of iNOS is beneficial or detrimental depends on many variables, such as the type of insult, the level and duration of expression, and the redox state of the tissue [41]. Interestingly, the activation of V2R in septic shock has been proposed to associate with adverse effects, such as selective vasodilation, prothrombosis, antidiuresis, and central nervous system changes [42]; as a consequence, a beneficial role has been recently ascribed to the inhibition of this receptor in the treatment of sepsis [10]. On these bases, the desmopressin-dependent induction of iNOS that we observed in HLMVECs appears particularly intriguing and its potential involvement in the adverse effects of V2R activation deserves to be addressed.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the centrality of dDAVP in clinical practice, much remains thus far to be understood about the impact of the drug on the integrity of endothelium [9]. Recently, Lopez and colleagues showed that the AVP-V2R axis is critical in the pathophysiology of severe microvascular hyperpermeability in sepsis, raising particular attention toward the dynamics of V2R activation in the microvasculature that may directly impact the outcome of septic patients [10]. In this context, we evaluate the effects of treatment with V2R agonist desmopressin on the viability and function of human pulmonary microvascular endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

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Desmopressin Stimulates Nitric Oxide Production in Human Lung Microvascular Endothelial Cells

et al. 2022

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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.

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Section: Discussionsupporting

confidence: 91%

“…Literature evidences have recently indicated that short-term incubations (1, 3, 6 h) with dDAVP have no cytotoxic effect on human endothelium in vitro [10]. Consistently,…”

Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Desmopressin Stimulates Nitric Oxide Production in Human Lung Microvascular Endothelial Cells

et al. 2022

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“…Therefore, copeptin is regarded as a predictor biomarker for assessment severity and prognosis of acquired pneumonia [26] . Lopez et al, showed that high AVP in bacterial sepsis and pneumonia is associated with increased pulmonary microvascular permeability, thus AVP antagonist tolvaptan may reduce the severity in septic patients [27] . Similarly, copeptin serum level is correlated with severity of ventilator associated pneumonia [28] .…”

Section: Physiological Profile Of Arginine Vasopressinmentioning

confidence: 99%

Arginine vasopressin and pathophysiology of COVID-19: An innovative perspective

Al-Kuraishy¹,

Al-Gareeb²,

Qusti

et al. 2021

Biomedicine & Pharmacotherapy

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In Covid-19, systemic disturbances may progress due to development of cytokine storm and dysregulation of and plasma osmolarility due to high release of pro-inflammatory cytokines and neuro-hormonal disorders. Arginine vasopressin (AVP) which is involve in the regulation of body osmotic system, body water content, blood pressure and plasma volume, that are highly disturbed in Covid-19 and linked with poor clinical outcomes. Therefore, this present study aimed to find the potential association between AVP serum level and inflammatory disorders in Covid-19. It has been observed by different recent studies that physiological response due to fever, pain, hypovolemia, dehydration, and psychological stress is characterized by activation release of AVP to counter-balance high blood viscosity in Covid-19 patients. In addition, activated immune cells mainly T and B lymphocytes and released pro-inflammatory cytokines stimulate discharge of stored AVP from immune cells, which in a vicious cycle trigger release of pro-inflammatory cytokines. Vasopressin receptor antagonists have antiviral and anti-inflammatory effects that may inhibit AVP-induced hyponatremia and release of pro-inflammatory cytokines in Covid-19. In conclusion, release of AVP from hypothalamus is augmented in Covid-19 due to stress, high pro-inflammatory cytokines, high circulating AngII and inhibition of GABAergic neurons. In turn, high AVP level leads to induction of hyponatremia, inflammatory disorders, and development of complications in Covid-19 by activation of NF-κB and NLRP3 inflammasome with release of pro-inflammatory cytokines. Therefore, AVP antagonists might be novel potential therapeutic modality in treating Covid-19 through mitigation of AVP-mediated inflammatory disorders and hyponatremia.

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Ultrasound evaluation of endothelial dysfunction in immunoglobulin-resistant children with acute Kawasaki disease

et al. 2022

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Purpose Clinically, some children with Kawasaki disease (KD) who do not respond to the rst application of gamma globulin therapy have a longer course of disease and a higher risk of coronary artery damage. The characteristics of vascular endothelial dysfunction in intravenous immune globulin (IVIG)-resistant patients during the acute phase are not well described. We aimed to determine whether indicators that detect the situation of the endothelium are useful parameters that can accurately re ect subclinical dysfunction in resistant patients and may assist in differentiating patients with KD at a higher risk of IVIG resistance.Methods Fifty IVIG-resistant KD children, 120 IVIG-responsive KD children, 70 febrile children with acute upper respiratory infection and 100 healthy controls were recruited, and indicators re ecting endothelial in ammation, including ow-mediated dilation (FMD), were measured. Receiver operating characteristic (ROC) curve analysis was utilized to determine the threshold values of these parameters associated with IVIG resistance. Multiple logistic regression analysis was performed to determine whether FMD was an independent predictor of IVIG-resistant patients.Results Compared with normal children, febrile children and IVIG-sensitive KD patients, IVIG-resistant patients had lower FMD (P<0.05) and higher carotid artery intima-media (CIMT) (P<0.05). Laboratory data demonstrated that the percentage of neutrophils (N %) and the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and serum procalcitonin (PCT) were signi cantly higher in the IVIG-resistant group than in the IVIG-responsive group, while the levels of albumin (ALB) and serum sodium were signi cantly lower (P< 0.05). PCT, Na+ and FMD exhibited AUCs of 0.727, 0.653 and 0.698, respectively, in predicting IVIG resistance in KD through ROC analysis. PCT > 1.69 ng/ml, Na+ <133.2 mmol/l and FMD <5.79% were independent predictors of IVIG resistance in KD (OR, 95% CI, P< 0.05).Conclusion More severe endothelial dysfunction, especially lower FMD, was present in IVIG-resistant patients than in IVIGresponsive patients. It is a helpful diagnostic tool that provides supportive criteria to detect KD patients at a higher risk of IVIG resistance when FMD<5.79% in children. What Is KnownChildren with Kawasaki disease have declined FMD and Stiffness index (SI) values, as well as raised carotid intima media thickness (CIMT) which are related to the severity of endothelial dysfunction in later stage after the onset.What is new 1. FMD is lower and CIMT is higher in KD patients with IVIG-resistance than those without, in the acute stage. 2. FMD and PCT have a negative relationship with each other, and FMD<5.79% reminds a chance of IVIG-resistance.

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Arginine vasopressin receptor 2 activation promotes microvascular permeability in sepsis

Cited by 7 publications

References 51 publications

Desmopressin Stimulates Nitric Oxide Production in Human Lung Microvascular Endothelial Cells

Desmopressin Stimulates Nitric Oxide Production in Human Lung Microvascular Endothelial Cells

Arginine vasopressin and pathophysiology of COVID-19: An innovative perspective

Ultrasound evaluation of endothelial dysfunction in immunoglobulin-resistant children with acute Kawasaki disease

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