Blood Pressure and Vascular Effects of Leptin in Humans

Abstract

BACKGROUND: Leptin may play a role in mediating obesity-related hypertension. However, its effects on the vasculature and blood pressure (BP) remain poorly defined in humans. METHODS: In the first study, we performed a short-term, placebo-controlled, randomized, double-blind, cross-over experiment investigating the actions of recombinant human leptin (r-metHuLeptin) in 15 nonobese adults. To compliment the acute study, we retrospectively analyzed available BP results from a previously performed 85-day, placebo-controlled, randomized, double-blind, parallel weight-loss study using r-metHuLeptin in 284 obese adults. RESULTS: In the acute study, conduit artery endothelial function determined by brachial flow-mediated dilatation (FMD) increased 2 hours following 0.2 mg . Kg(1) subcutaneously (SC) of r-metHuLeptin versus placebo (+3.3% versus -2.8%, P = .02). BP remained unchanged 4 hours after injections. In the retrospective analysis of the weight loss study data, 10 mg every day before noon (QAM), 10 mg every day after noon (QPM), or 10 mg twice a day (BID) SC of r-metHuLeptin was found to not alter the degree of weight loss (-3.2 +/- 3.7 versus -2.9 +/- 3.2 Kg, P = .54), change in systolic (-1.6 + 12.9 versus -2.0 +/- 13.9 mmHg, P = .85) and diastolic BP (-0.2 +/- 8.7 versus -1.5 +/- 8.6, P = .30), as well as heart rate (-1.4 +/- 10.7 versus -1.4 +/- 10.4 beats/min, P = .98) compared to placebo. CONCLUSIONS: In our acute study, marked hyperleptinemia rapidly enhanced endothelial function and did not alter BP. The available data from a longer-term study in healthy obese adults did not demonstrate a significant effect of hyperleptinemia upon BP. These combined findings do not support a direct role for leptin in linking obesity to hypertension, however more studies are required to corroborate these observations.