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Pathophysiological role of leptin in obesity-related hypertension
Megumi Aizawa-Abe, … , Yasunao Yoshimasa, Kazuwa Nakao
Megumi Aizawa-Abe, … , Yasunao Yoshimasa, Kazuwa Nakao
Published May 1, 2000
Citation Information: J Clin Invest. 2000;105(9):1243-1252. https://doi.org/10.1172/JCI8341.
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Article

Pathophysiological role of leptin in obesity-related hypertension

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Abstract

To explore the pathophysiological role of leptin in obesity-related hypertension, we examined cardiovascular phenotypes of transgenic skinny mice whose elevated plasma leptin concentrations are comparable to those seen in obese subjects. We also studied genetically obese KKAy mice with hyperleptinemia, in which hypothalamic melanocortin system is antagonized by ectopic expression of the agouti protein. Systolic blood pressure (BP) and urinary catecholamine excretion are elevated in transgenic skinny mice relative to nontransgenic littermates. The BP elevation in transgenic skinny mice is abolished by α1-adrenergic, β-adrenergic, or ganglionic blockers at doses that do not affect BP in nontransgenic littermates. Central administration of an α-melanocyte–stimulating hormone antagonist causes a marked increase in cumulative food intake but no significant changes in BP. The obese KKAy mice develop BP elevation with increased urinary catecholamine excretion relative to control KK mice. After a 2-week caloric restriction, BP elevation is reversed in nontransgenic littermates with the Ay allele, in parallel with a reduction in plasma leptin concentrations, but is sustained in transgenic mice overexpressing leptin with the Ay allele, which remain hyperleptinemic. This study demonstrates BP elevation in transgenic skinny mice and obese KKAy mice that are both hyperleptinemic, thereby suggesting the pathophysiological role of leptin in some forms of obesity-related hypertension.

Authors

Megumi Aizawa-Abe, Yoshihiro Ogawa, Hiroaki Masuzaki, Ken Ebihara, Noriko Satoh, Hidenori Iwai, Naoki Matsuoka, Tatsuya Hayashi, Kiminori Hosoda, Gen Inoue, Yasunao Yoshimasa, Kazuwa Nakao

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