AVP inhibits LPS- and IL-1β-stimulated NO and cGMP via V₁receptor in cultured rat mesangial cells

Abstract

The present study examined how arginine vasopressin (AVP) affects nitric oxide (NO) metabolism in cultured rat glomerular mesangial cells (GMC). GMC were incubated with test agents and nitrite, and intracellular cGMP content, inducible nitric oxide synthase (iNOS) mRNA, and iNOS protein were analyzed by the Griess method, enzyme immunoassay, and Northern and Western blotting, respectively. AVP inhibited lipopolysaccharide (LPS)- and interleukin-1β (IL-1β)-induced nitrite production in a dose- and time-dependent manner, with concomitant changes in cGMP content, iNOS mRNA, and iNOS protein. This inhibition by AVP was reversed by V1- but not by oxytocin-receptor antagonist. Inhibition by AVP was also reproduced on LPS and interferon-γ (IFN-γ). Protein kinase C (PKC) inhibitors reversed AVP inhibition, whereas PKC activator inhibited nitrite production. Although dexamethasone and pyrrolidinedithiocarbamate (PDTC), inhibitors of nuclear factor-κB, inhibited nitrite production, further inhibition by AVP was not observed. AVP did not show further inhibition of nitrite production with actinomycin D, an inhibitor of transcription, or cycloheximide, an inhibitor of protein synthesis. In conclusion, AVP inhibits LPS- and IL-1β-induced NO production through a V1 receptor. The inhibitory action of AVP involves both the activation of PKC and the transcription of iNOS mRNA in cultured rat GMC.

Review article: Organ per fusion/permeabilityrelated effects of norepinephrine and vasopressin in sepsis

“…Arginine-vasopressin preferentially induces vasoconstriction of efferent arterioles over afferent arterioles in isolated human kidney vessel preparations in vitro, as well as inhibiting lipopolysaccharidesand interleukin-(IL) 1ß-stimulated NO (inducible NO synthase) in cultured rat glomerular mesangial cells. 56,57 Therefore, AVP can restore renal blood flow (particularly cortical blood flow) and glomerular filtration pressure in septic/endotoxic conditions. 58 Consequently, urine output as well as creatinine clearance can be substantially improved in patients exhibiting severe septic shock and treated with AVP.…”

Défaillance rénale

“…L'arginine vasopressine inactive les canaux potassiques ATPdépendants [22] et, de ce fait, diminue la résistance des vaisseaux aux eff ets de la noradrénaline [14] et de l'angiotensine II [7]. L'arginine vasopressine diminue la synthèse du NO (en conséquence d'une diminution de l'expression de la NO synthétase inductible) et du guanosine monophosphate cyclique (GMPc) [23]. Il en résulte une atténuation de la vasodilatation artérielle et une diminution de la résistance au traitement vasopresseur durant le sepsis.…”

New Methods to Evaluate Endothelial Function: Evaluation of Endothelial Function by Hemoglobin-Nitric Oxide Complex Using Electron Paramagnetic Resonance Spectroscopy

“…HbNO has a characteristic EPR spectrum, and hence endogenous Hb acts as a spin trapping agent for NO in LPS-treated (24,25) and NO donor-administered (26,27) animals. In addition, the HbNO signal has been successfully detected in untreated animals and human blood using the EPR method (12,28,29,31). However, there were still some difficulties in obtaining a fine HbNO signal because of the existence of paramagnetic compounds that give a strong EPR signal overlapping the same region to HbNO (26, 33 -37).…”

“…Several methods for the quantitation of NO such as chemiluminescence (5), methemoglobin formation (6), and electron paramagnetic resonance (EPR) spectroscopy of nitrosyl-metal complexes (7) have been developed (8). The Griess and cGMP methods have been widely used to measure NO production in vivo (9,10) and in vitro (11,12), but these values do not always reflect the concentration of NO, because of their poor specificities for blood NO. EPR spectroscopy is a technique used for the detection and measurement of free radical species.…”