Kinin B1 Receptor Promotes Neurogenic Hypertension Through Activation of Centrally Mediated MechanismsNovelty and Significance [Brain]

In this study, we tested the hypothesis that activation of B1R in the brain is involved in the pathogenesis of hypertension, using the deoxycorticosterone acetate–salt model of neurogenic hypertension in wild-type and B1R knockout mice. Deoxycorticosterone acetate–salt treatment in wild-type mice led to significant increases in B1R mRNA and protein levels and bradykinin levels, enhanced gene expression of carboxypeptidase N supporting an increase in the B1R ligand, associated with enhanced blood pressure, inflammation, sympathoexcitation, autonomic dysfunction, and impaired baroreflex sensitivity, whereas these changes were blunted or prevented in B1R knockout mice. B1R stimulation was further shown to involve activation of the ASK1-JNK-ERK1/2 and NF-κB pathways in the brain. To dismiss potential developmental alterations in knockout mice, we further used B1R blockade selectively in the brain of wild-type mice. Supporting the central origin of this mechanism, intracerebroventricular infusion of a specific B1R antagonist, attenuated the deoxycorticosterone acetate-salt–induced increase in blood pressure in wild-type mice. Our data provide the first evidence of a central role for B1R-mediated inflammatory pathways in the pathogenesis of deoxycorticosterone acetate–salt hypertension and offer novel insights into possible B1R-targeted therapies for the treatment of neurogenic hypertension.

Source: Hypertension - November 8, 2017 Category: Cardiology Authors: Srinivas Sriramula, Eric Lazartigues Tags: Animal Models of Human Disease, Inflammation, Oxidant Stress, High Blood Pressure, Hypertension Original Articles Source Type: research