Inflammation and Hypertension: The Interplay of Interleukin-6, Dietary Sodium, and the Renin-Angiotensin System in Humans

Abstract

Background Prior evidence suggests a link between inflammation and hypertension. Interleukin-6 (IL-6) has been implicated in animal studies to play an important role in angiotensin II (ANGII) mediated hypertension. The aim of this study was to examine the relationship of IL-6 and renin-angiotensin system (RAS) activity in human hypertension. Methods Data from 385 hypertensives and 196 normotensives are included in this report. Blood pressure and laboratory evaluation were performed on liberal and low sodium diets. IL-6 response to an ANGII infusion was evaluated to assess the effect of acute RAS activation. Results Hypertensives had higher baseline IL-6 and C-reactive protein (CRP) compared with normotensives on both diets. IL-6 increased in response to ANGII in hypertensives and normotensives (28% in hypertensives, 31% in normotensives, p = < 0.001 for change from baseline). In the setting of RAS activation by a low salt diet, multivariate regression analysis adjusted for age, BMI, gender, race and hypertension status demonstrated an independent positive association of PRA with CRP (beta = 0.199, p<0.0001). There was no significant difference in IL-6 or CRP levels between liberal and low sodium diets. Conclusion These findings confirm an association between hypertension and inflammation and provide human data supporting previous evidence from animal studies that IL-6 plays a role in ANGII mediated hypertension. Notably, compared to levels on a liberal sodium diet, neither IL-6 or CRP were higher with activation of the RAS by a low salt diet indicating that a low sodium diet is not inflammatory despite increased RAS activity.

The C4280A (rs5705) gene polymorphism of the renin (REN) gene is associated with risk of developing coronary artery disease, but not with restenosis after coronary stenting

“…The restenosis is the arterial wall's healing response to mechanical injury and comprises two main processes, neointimal hyperplasia (i.e., smooth muscle migration/proliferation, extracellular matrix deposition) and vessel remodeling (Costa and Simon, 2005). In the literature, there has been evidence that the activation of the renin-angiotensin system (RAS) induces the production of pro-inflammatory cytokines, proliferation and vasoconstriction on the vasculature, and in consequence can contribute to initiation and progression of atherosclerosis (Chamarthi et al, 2011;Mehta and Griendling, 2007;van Thiel et al, 2015;Pacurari et al, 2014). In addition, RAS has been implicated in the pathogenesis of neointimal hyperplasia, and a role for angiotensin II in the migration and proliferation of vascular smooth muscle cells in restenosis has been reported (Pacurari et al, 2014;Valente et al, 2012;Yao et al, 2012).…”

Mild Hypercholesterolemia Blunts the Proinflammatory and Prothrombotic Effects of Hypertension on the Cerebral Microcirculation

“…All of the established risk factors for cardiovascular disease, including hypertension (HTN) and hypercholesterolemia (HCh), are now recognized to induce a systemic inflammatory response that appears to underlie the vascular dysfunction that accompanies these conditions. Hypertensive patients exhibit elevated plasma levels of inflammatory mediators such as high-sensitive C-reactive protein, 1,2 interleukin 6 (IL-6), 2 interferon-inducible protein-10, and IL-4, IL-7, and IL-13. 3 Similarly, high-sensitive C-reactive protein, 4,5 chemokine CXC ligand 5 (CXCL5), 6 xanthine oxidase activity, IL-1 and IL-6 are all increased in plasma of HCh patients.…”

Interplay of Hypertension, Inflammation, and Angiotensin II

“…In the present issue of American Journal of Hypertension, Chamarthi et al 5 further demonstrated a relationship between CRP, IL-6, and hypertension by comparing hypertensives to normotensives. The study also showed a significant rise in IL-6 in response to angiotensin II infusion in both hypertensives and normotensives.…”