Pathophysiological role of leptin in obesity-related hypertension

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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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 KKA(y) 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 KKA(y) 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 A(y) allele, in parallel with a reduction in plasma leptin concentrations, but is sustained in transgenic mice overexpressing leptin with the A(y) allele, which remain hyperleptinemic. This study demonstrates BP elevation in transgenic skinny mice and obese KKA(y) mice that are both hyperleptinemic, thereby suggesting the pathophysiological role of leptin in some forms of obesity-related hypertension.

Original languageEnglish
Pages (from-to)1243-1252
Number of pages10
JournalJournal of Clinical Investigation
Volume105
Issue number9
DOIs
Publication statusPublished - May 2000
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Aizawa-Abe, M., Ogawa, Y., Masuzaki, H., Ebihara, K., Satoh, N., Iwai, H., ... Nakao, K. (2000). Pathophysiological role of leptin in obesity-related hypertension. Journal of Clinical Investigation, 105(9), 1243-1252. https://doi.org/10.1172/JCI8341