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Systemic leukotriene B 4 receptor antagonism lowers arterial blood pressure and improves autonomic function in the spontaneously hypertensive rat
Author(s) -
Marvar Paul J.,
Hendy Emma B.,
Cruise Thomas D.,
Walas Dawid,
DeCicco Danielle,
Vadigepalli Rajanikanth,
Schwaber James S.,
Waki Hidefumi,
Murphy David,
Paton Julian F. R.
Publication year - 2016
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp272065
Subject(s) - leukotriene b4 , medicine , blood pressure , inflammation , spontaneously hypertensive rat , endocrinology , pathophysiology of hypertension , brainstem , receptor , leukotriene , systemic inflammation , pharmacology , asthma
Key points 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) support a role for leukotriene B 4 (LTB 4 ), a potent chemoattractant involved in the inflammatory response, but its mode of action is poorly understood. In the SHR, we observed an increase in T cells and macrophages in the brainstem; in addition, gene expression profiling data showed that LTB 4 production, degradation and downstream signalling in the brainstem of the SHR are dynamically regulated during hypertension. When LTB 4 receptor 1 (BLT1) receptors were blocked with CP‐105,696, arterial pressure was reduced in the SHR compared to the normotensive control and this reduction was associated with a significant decrease in systolic blood pressure (BP) indicators. These data provide new evidence for the role of LTB 4 as an important neuro‐immune pathway in the development of hypertension and therefore may serve as a novel therapeutic target for the treatment of neurogenic hypertension.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) support a role for leukotriene B 4 (LTB 4 ), a potent chemoattractant involved in the inflammatory response. However, the mechanism for LTB 4 ‐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 LTB 4 production, degradation and downstream signalling in the brainstem of the SHR are dynamically regulated during hypertension. Chronic blockade of the LTB 4 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 LTB 4 as an important neuro‐immune pathway in the development of hypertension and therefore may serve as a novel therapeutic target for the treatment of neurogenic hypertension.