title: Experimental hyperleptinemia acutely increases vasoconstrictory sympathetic nerve activity in healthy humans.
abstract: BACKGROUND
  Obesity and arterial hypertension are tightly connected. Obese individuals show significant elevation of vasoconstrictory muscle sympathetic nerve activity (MSNA). Obesity-related hyperleptinemia might play a key role in mediating these effects. Leptin is synthesized in proportion to body fat mass and activates SNA in animal models. In humans, however, direct evidence linking hyperleptinemia to sympathetic activation has not yet been established. In the present study, we characterize the effects of acute hyperleptinemia on microneurographically recorded SNA in humans.
  
  
  METHODS
  In a balanced, double-blind crossover design, 12 healthy normal-weight males received an iv bolus of leptin or placebo. MSNA (bursts per minute) was continuously recorded using a microneurographic technique. Ten-minute periods were analyzed at resting periods before (t-100) and at 20 (t20), 60 (t60), and 140 (t140) minutes after substance administration. Blood pressure and heart rate (HR) were recorded simultaneously.
  
  
  RESULTS
  Baseline values of MSNA, blood pressure, and HR were comparable in both conditions (MSNA: t-100, 24.3 ± 1.6 vs 22.7 ± 1.7, not significant). After application of leptin, MSNA showed a significant increase (t20, 31.0 ± 1.9 vs. 24.9 ± 1.8, P = .05) that persisted until the end of the experiment (t60, P = .008; t140, P = .004). There were no significant changes in blood pressure and HR.
  
  
  CONCLUSIONS
  Acute experimental hyperleptinemia has significant central nervous excitatory effects on vasoconstrictory sympathetic outflow as measured by MSNA in healthy men. These results suggest that leptin acts as an important mediator linking obesity to elevated MSNA and potentially to the development of hypertension.
authors: Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Campus Lübeck, D-23538 Lübeck, Germany.
authors: Felix
authors: F
authors: Machleidt
authors: Paul
authors: P
authors: Simon
authors: Alexander F
authors: AF
authors: Krapalis
authors: Manfred
authors: M
authors: Hallschmid
authors: Hendrik
authors: H
authors: Lehnert
authors: Friedhelm
authors: F
authors: Sayk
mesh_terms: D000208:Acute Disease; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000139:chemically induced* / Q000503:physiopathology; D007275:Injections, Intravenous; D020738:Leptin / Q000009:adverse effects / Q000097:blood* / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D020738:Leptin