Renal Denervation Reduces Monocyte Activation and Monocyte–Platelet Aggregate Formation

Hypertension contributes significantly to the high cardiovascular morbidity and mortality rates worldwide. While acknowledging the complexity and multifactorial pathogenesis of hypertension, it has been suggested that activation of the sympathetic nervous system (SNS) is an important contributor in at least 50% of cases. Persistent sympathetic activation initiates and sustains elevated blood pressure (BP) via various pathways, including renal (sodium and water retention), humoral (activation of the renin–angiotensin system), peripheral (vasoconstriction), and other mechanisms. Sustained sympathetic activation has also been closely linked to a range of clinical adverse consequences, such as left ventricular hypertrophy, progression of renal disease, and others. Catheter-based renal denervation (RDN) is a relatively novel therapeutic approach used primarily in the context of resistant hypertension aimed at targeting sympathetic overactivity commonly encountered in these patients. Indeed, we and others have demonstrated that RDN reduces both renal sympathetic activity (by ≤42% in obese hypertensive dogs and by ≤47% in patients with resistant hypertension) and muscle sympathetic nerve Abstract—Overactivation of renal sympathetic nervous system and low-grade systemic inflammation are common features of hypertension. Renal denervation (RDN) reduces sympathetic activity in patients with resistant hypertension. However, its effect on systemic inflammation has not been examined. We prospectively investigated the effect of RDN on monocyte activation and inflammation in patients with uncontrolled hypertension scheduled for RDN. Ambulatory blood pressure, monocyte, and monocyte subset activation and inflammatory markers were assessed at baseline, 3 months, and 6 months after procedure in 42 patients. RDN significantly lowered blood pressure at 3 months (150.5±11.2/81.0±11.2 mm Hg to 144.7±11.8/77.9±11.0 mm Hg), which was sustained at 6 months (144.7±13.8/78.6±11.0 mm Hg). Activation status of monocytes significantly decreased at 3 months (P<0.01) and 6 months (P<0.01) after the procedure. In particular, classical monocyte activation was reduced at 6 months (P<0.05). Similarly, we observed a reduction of several inflammatory markers, including monocyte–platelet aggregates (3 months, P<0.01), plasma monocyte chemoattractant protein-1 levels (3 months, P<0.0001; 6 months, P<0.05), interleukin-1β (3 months, P<0.05; 6 months, P<0.05), tumor necrosis factor-α (3 months, P<0.01; 6 months, P<0.05), and interleukin-12 (3 months, P<0.01; 6 months, P<0.05). A positive correlation was observed between muscle sympathetic nerve activity and monocyte activation before and after the procedure. These results indicate that inhibition of sympathetic activity via RDN is associated with a reduction of monocyte activation and other inflammatory markers in hypertensive patients. These findings point to a direct interaction between the inflammatory and sympathetic nervous system, which is of central relevance for the understanding of beneficial cardiovascular effects of RDN. (Hypertension. 2017;69:323-331. DOI: 10.1161/HYPERTENSIONAHA.116.08373.) • Online Data Supplement