Substantial Reduction in Single Sympathetic Nerve Firing After Renal Denervation in Patients With Resistant Hypertension

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...

Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel on Renal Sympathetic Denervation

“…The first Symplicity trial demonstrated long-term reductions in MSNA after RDN in a larger patient population (N ¼ 24) (25). However, in this study, the reductions in MSNA (approximately 10%) measured 3 months after RDN were considerably less than what had been reported in the earlier report.…”

Sustained Reduction of Blood Pressure With Baroreceptor Activation Therapy

“…Thus, there may be some apparent differences in the efficacy of renal denervation compared with BAT, even though both techniques are indicated to reduce sympathetic traffic. 4,11,12 It is conceivable that these differences explain, at least in part, why BAT can still reduce blood pressure in patients who had previous renal denervation. 13 In a small group of predominantly female patients, the initial fall in blood pressure was followed by unresponsiveness to stimulation.…”

Sympathetic Nervous System and Hypertension

“…In 25 patients with resistant hypertension, renal denervation decreased blood pressure, multi-unit and single unit muscle sympathetic nerve activity at 3 months. 19 All features of single unit muscle sympathetic nerve activity were decreased: firing rate, firing probability, and incidence of multiple spikes. These findings emphasize the importance of interrupting excitatory afferent renal nerve pathways to the brain in mediating the generalized sympathoinhibition and blood pressure reduction.…”