No abstract

A rterial hypertension is a major contributor to global cardiovascular morbidity and mortality.1 Although the pathophysiology of hypertension is complex and multifactorial, sympathetic activation is a pivotal mechanism contributing to the development and perpetuation of high BP and its adverse cardiovascular consequences. [2][3][4][5][6][7] Many patients with essential hypertension are characterized by increased sympathetic nerve firing rates in postganglionic fibers directed to the skeletal muscle vascular bed, 8 accompanied by enhanced cardiac and renal sympathetic nerve activity. 2,3,9 The magnitude of sympathetic excitation is directly linked to the disease progression and contributes considerably to hypertension-related end organ damage including left ventricular hypertrophy 10 and left ventricular diastolic dysfunction.11 Although evidence for increased sympathetic outflow to the periphery has been determined primarily by using multi-unit muscle sympathetic nerve activity (MSNA) recordings, more recent findings applying technically challenging single nerve recording have demonstrated that firing patterns of single muscle sympathetic fibers provide more specific and quantitative information on central sympathetic drive. Indeed, in patients with mild essential hypertension, sympathetic discharge from single muscle vasoconstrictor neurons is more pronounced than in moderate and severe hypertension, whereas multi-unit MSNA is comparable across all grades of the disease. 6 Assessment of the pattern of singleunit vasoconstrictor firing has also provided evidence for a distinct difference in central sympathetic outflow between lean and obese hypertensive patients. 12 Furthermore, a direct relationship between single nerve firing rates and left ventricular mass, as assessed by magnetic resonance imaging, has recently been demonstrated in essential hypertension. 13Abstract-Renal denervation (RDN) has been shown to reduce blood pressure (BP) and muscle sympathetic nerve activity (MSNA) in patients with resistant hypertension. The mechanisms underlying sympathetic neural inhibition are unknown. We examined whether RDN differentially influences the sympathetic discharge pattern of vasoconstrictor neurons in patients with resistant hypertension. Standardized office BP, single-unit MSNA, and multi-unit MSNA were obtained at baseline and at 3-month follow-up in 35 patients with resistant hypertension. Twenty-five patients underwent RDN, and 10 patients underwent repeated measurements without RDN (non-RDN). Baseline BP averaged 164/93 mm Hg (RDN) and 164/87 mm Hg (non-RDN) despite use of an average of 4.8±0.4 and 4.4±0.5 antihypertensive drugs, respectively. Mean office BP decreased significantly by −13/−6 mm Hg for systolic BP (P<0.001) and diastolic BP (P<0.05) with RDN but not in non-RDN at 3-month follow-up. RDN moderately decreased multi-unit MSNA (79±3 versus 73±4 bursts/100 heartbeats; P<0.05), whereas all properties of single-unit MSNA including firing rates of individual vasoconstrictor fibers (43±5 versus 27±3 s...

U ncontrolled blood pressure (BP) remains the leading cause of cardiovascular morbidity and mortality globally.1 Despite the availability of potent antihypertensive drugs, only 53% of patients with documented hypertension achieve target BP levels.2 Although determining the exact prevalence of patients with resistant hypertension (RH) remains complex, data available from United States and Europe have indicated that resistance to pharmacological treatment occurs in 13% of treated patients with elevated BP.3 Furthermore, the prevalence 3 and incidence of RH is projected to increase progressively. 4 Patients with true RH commonly display evidence of end organ damage 5 and are at high risk for cardiovascular events.6 Accordingly, even a mild reduction in BP has been demonstrated to reduce overall cardiovascular morbidity and mortality substantially. 7,8 As part of the complex and multifactorial pathophysiology of RH, 9 enhanced sympathetic activation is a critical contributor to BP elevation. [10][11][12] In fact, both low-risk subjects with high-normal BP 13 and high-risk patients with RH 14 have increased muscle sympathetic nerve activity (MSNA). Furthermore, patients with RH are characterized by persistent sympathetic activation as evidenced by increased single-and multiunit MSNA and augmented renal noradrenaline spillover. [14][15][16] In this context, catheter-based sympathetic renal denervation (RDN) provides a rational approach in patient management given that both efferent and afferent renal nerves are pivotal in the initiation and maintenance of elevated BP.17 Indeed, RDN has been associated with substantial and sustained BP reduction, decreased noradrenaline spillover, and postganglionic efferent single-and multiunit MSNA in RH. [14][15][16][18][19][20][21] Although the majority of currently available results with RDN are promising and the rationale for the use of this approach for other conditions characterized by sympathetic excitation is apparent, not all studies demonstrated a reduction in MSNA after RDN. 22 Furthermore, renal nerves have the capacity to regrow, which may affect the long-term effects of the procedure. At this stage, it is unclear whether any reinnervation that may occur is of functional relevance. 23 Likewise, the long-term effect of RDN on MSNA has not yet Abstract-Renal denervation (RDN) reduces muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in resistant hypertension. Although a persistent BP-lowering effect has been demonstrated, the long-term effect on MSNA remains elusive. We investigated whether RDN influences MSNA over time. Office BP and MSNA were obtained at baseline, 3, 6, and 12 months after RDN in 35 patients with resistant hypertension. Office BP averaged 166±22/88±19 mm Hg, despite the use of an average of 4.8±2.1 antihypertensive drugs. Baseline MSNA was 51±11 bursts/min ≈2-to 3-fold higher than the level observed in healthy controls. Mean office systolic and diastolic BP significantly decreased by -12.6±18.3/-6.5±9.2, -16.1±25.6/-8.6±12.9, and -21.2±29....