Leptin induces direct vasodilation through distinct endothelial mechanisms.

Abstract

In this study, we reveal that leptin evokes an acute hypotensive effect in 6-hydroxydopamine sympathectomized rats (response to maximal leptin dose, mean blood pressure: from 92 +/- 4 to 78 +/- 2 mmHg, P < 0.01). This hemodynamic effect is related to a direct action of the hormone on vascular tone, since in aortic and mesenteric rings increasing doses of leptin evoke a dose-dependent vasorelaxation (aorta: from 3 +/- 1 to 36 +/- 3, n = 15; mesenteric: from 6 +/- 1 to 30 +/- 5, n = 10), which is impaired by endothelial denudation. In particular, leptin-evoked vasorelaxation is impaired by nitric oxide synthase inhibition in aorta (delta% of maximal response: from 36 +/- 3 to 3 +/- 1, P < 0.01) and by endothelium-derived hyperpolarizing factor (EDHF) inhibition in mesenteric arteries (delta% of maximal response: from 30 +/- 5 to 7 +/- 2, P < 0.01), suggesting that vasorelaxation evoked by leptin is heterogeneous and related to the vascular bed. Finally, the inhibition of nitric oxide synthase by NG-nitro-L-arginine-methyl ester does not modify blood pressure response to leptin, suggesting a predominant role of the EDHF mechanism in the hypotensive effect of leptin.

Leptin is favourably associated with vascular function in obese Caucasians, but not in obese Africans

“…Since leptin's positive [18][19][20] and negative 14,15 influences on vascular function has been reported, partial correlations were performed while adjusting for age to determine if leptin is associated with the obese African group's possible decreased vascular function, or the obese Caucasian group's possible normal or enhanced vascular function. By doing so, leptin failed to show any associations with the vascular profile in the obese African group.…”

“…Additionally, leptin correlated negatively with TPR and positively with C W , implicating leptin as a possible role player in the accommodating effect observed in the obese Caucasian group, but not in the obese African group. One may speculate that this accommodating effect could be the result of leptin's angiogenic 37,38 and/or vasodilatory [18][19][20] effect, which would lead to decreased TPR and increase C W .…”

“…Results in sodium retention and blood pressure elevation 19 Increases plasma angiotensin II, increasing vasoconstriction and blood pressure 19 (e) Leptin has depressor effects by causing vasodilation through nitric oxide dependent and independent mechanisms [18][19][20] What this study adds (a) This is the first study to compare the associations of chronically elevated leptin levels with cardiovascular function between obese African and Caucasian women (b) Chronically elevated leptin levels are favourably associated with vascular function in obese Caucasian women, but not in obese African women African women is supported by results from a recent publication, 21 which showed leptin to be independently associated with SBP and decreased C W in obese hypertensive African women. Since the SBP and DBP of both obese African and Caucasian groups were in the normotensive range, 39 the presence of prominent positive associations between leptin and vascular function in the obese Caucasians and the lack thereof in the obese Africans, could indicate that leptin predominantly exerts pathological influences on vascular function in obese African women, as determined previously in obese hypertensive African women.…”

“…Leptin has been shown, after acute administration, to cause vasodilation through nitric oxide dependent and independent mechanisms, decreasing TPR, increasing C W and decreasing blood pressure. [18][19][20] The above-mentioned studies determined that leptin has pressor and depressor effects that would result in decreased or increased vascular function and elevated or reduced blood pressure as serum leptin levels increase with increased adiposity. Associations of chronically elevated leptin levels with cardiovascular function in obese African women are limited 21 and comparisons of leptin's associations with cardiovascular function between Africans and Caucasians absent.…”

Dietary determinants of subclinical inflammation, dyslipidemia and components of the metabolic syndrome in overweight children: a review

“…32 In obese 7-11-year-old children, no association was found between leptin and energy, fat or carbohydrate intake. 33 Intravenous leptin in animals increases sympathetic nerve activation 34 and produces endothelium-dependent vasodilation, 35 resulting in variable effects on BP. Although several adult studies have found increased leptin concentrations are correlated with hypertension, 5 other studies have not.…”