Bradykinin B1Receptor-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.