Systemic leukotriene B4 receptor antagonism lowers arterial blood pressure and improves autonomic function in the spontaneously hypertensive rat

Emma Hendy, Paul Marvar, Tom Cruise, Dawid Walas, Danielle DeCicco, Rajanikanth Vadigepalli, James Schwaber, Hidefumi Waki, David Murphy, Julian F R Paton

Research output: Contribution to journalArticle (Academic Journal)peer-review

11 Citations (Scopus)
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Abstract

Accumulating evidence indicates an association between hypertension and chronic systemic inflammation in both human hypertension and experimental animal models. Previous studies in the spontaneously hypertensive rat (SHR) supports a role for leukotriene B4 (LTB4), a potent chemoattractant involved in the inflammatory response. However the mechanism for LTB4 mediated inflammation in hypertension is poorly understood. Here we report in the SHR, increased brainstem infiltration of T cells and macrophages plus gene expression profiling data showing that LTB4 production, degradation and downstream signalling in the brainstem of the SHR are dynamically regulated during hypertension. Chronic blockade of the LTB4 receptor 1 (BLT1) receptor with CP-105,696, reduced arterial pressure in the SHR compared to the normotensive control and this reduction was associated with a significant decrease in low and high frequency spectra of systolic blood pressure, and an increase in spontaneous baroreceptor reflex gain (sBRG). These data provide new evidence for the role of LTB4 as an important neuroimmune pathway in the development of hypertension and therefore may serve as a novel therapeutic target for the treatment of neurogenic hypertension.
Original languageEnglish
Pages (from-to)5975-5989
Number of pages15
JournalJournal of Physiology
Volume594
Issue number20
Early online date27 May 2016
DOIs
Publication statusPublished - 15 Oct 2016

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