TY - JOUR
T1 - Experimental hyperleptinemia acutely increases vasoconstrictory sympathetic nerve activity in healthy humans
AU - Machleidt, Felix
AU - Simon, Paul
AU - Krapalis, Alexander F.
AU - Hallschmid, Manfred
AU - Lehnert, Hendrik
AU - Sayk, Friedhelm
PY - 2013/3/1
Y1 - 2013/3/1
N2 - 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 (t 60), 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; t 140, 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.
AB - 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 (t 60), 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; t 140, 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.
UR - http://www.scopus.com/inward/record.url?scp=84874922581&partnerID=8YFLogxK
U2 - 10.1210/jc.2012-3009
DO - 10.1210/jc.2012-3009
M3 - Journal articles
C2 - 23393176
AN - SCOPUS:84874922581
SN - 0021-972X
VL - 98
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 3
ER -