Bradykinin B1 Receptor-Mediated Changes in Renal Hemodynamics during Endotoxin-Induced Inflammation

Abstract

Abstract. Kinins have been shown to influence renal hemodynamics and function. Under physiologic conditions, most kinin effects involve bradykinin B2receptors, but bradykinin B1receptors are often induced during inflammation. The purpose of this study was to examinein vivothe effects of bradykinin B1receptor activation on renal hemodynamics under normal and inflammatory conditions. In anesthetized rats, activation of bradykinin B1receptors by arterial infusion of bradykinin B1receptor agonist des-Arg9-bradykinin reduced renal plasma flow and GFR. Prior administration (18 h) of lipopolysaccharide to induce inflammation resulted in a larger bradykinin B1receptor-induced reduction in renal plasma flow. Values of other parameters remained unchanged, thus resulting in an increased filtration fraction. The presence and the functionality of the bradykinin B1receptor at the level of glomerular afferent and efferent arterioles were studied by mRNA expression analysis and intracellular calcium ([Ca2+]i) mobilization studies. Stimulation with des-Arg9-bradykinin of microdissected afferent arterioles from control and lipopolysaccharide-treated rats induced [Ca2+]imobilization without any significant difference in amplitude between control and lipopolysaccharidetreated rats. However, des-Arg9-bradykinin only induced [Ca2+]imobilization in efferent arterioles from lipopolysaccharide-treated rats. It is suggested that activation of bradykinin B1receptors located along the efferent arteriole may participate in the modification of renal hemodynamics in inflammatory states.

Angiotensin-Converting Enzyme 2 in the Pathogenesis of Renal Abnormalities Observed in COVID-19 Patients

“…Under physiological conditions, most of the KKS actions are mediated by B2 activation and the B1 is induced in inflammatory processes (Klein et al, 2010). Infusion of low concentrations of desArg 9 BK in anesthetized rats decreased renal blood flow and GFR, which was associated with increased renal vascular resistance and opposite effects to those of BK (Schanstra et al, 2000;Zhang et al, 2018). B1 activation is associated with enhanced transcription of NFκB, which has a positive feedback on B1 expression and promotes the release of cytokines and chemokines, ultimately resulting in the accumulation of leukocytes (Klein et al, 2010).…”

ACE2: Its potential role and regulation in severe acute respiratory syndrome and COVID‐19

“…Bradykinin mediates its biological effects via receptors B1 and B2 and is degraded by two key kinases, ACE and neutral endopeptidase (Imai et al, 2007). Inflammatory cytokines may also induce the expression of B1 receptors (Schanstra et al, 2000), although the function of bradykinin and B1 receptors in inflammation caused by Ang II remains unclear. Unlike ACE, ACE2 does not metabolize bradykinin but catalytically inactivates the (des‐Arg9)‐bradykinin and lys(des‐Arg9)‐bradykinin metabolites (Donoghue et al, 2000; Vickers et al, 2002).…”