Role of the paraventricular nucleus of the hypothalamus in the sympathoexcitatory effects of leptin

Zhigang Shi, Baoxin Li, Virginia Brooks

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Leptin binds to receptors in multiple hypothalamic nuclei to increase sympathetic nerve activity; however, the neurocircuitry is unclear. Here, using anesthetized male Sprague-Dawley rats, we investigated the role of the paraventricular nucleus of the hypothalamus. Intracerebroventricular injection of leptin slowly increased lumbar sympathetic nerve activity (LSNA), heart rate, mean arterial pressure, and baroreflex control of LSNA and heart rate. Inhibition of the paraventricular nucleus with muscimol completely reversed leptin's effects. Blockade of paraventricular melanocortin 3/4 receptors with SHU9119 or ionotropic glutamate receptors with kynurenate, alone or together, each partially reversed the effects of leptin, implicating increased activation of glutamate and melanocortin 3/4 receptors. Conversely, although blockade of neuropeptide Y Y1 receptors in the paraventricular nucleus increased LSNA, mean arterial pressure, and heart rate, these responses were prevented by intracerebroventricular or arcuate nucleus injections of leptin, suggesting that, at least in part, leptin also increases sympathetic nerve activity by suppression of tonic neuropeptide Y inhibitory inputs from the arcuate nucleus. Injection of the melanocortin 3/4 receptor agonist melanotan-II into the paraventricular nucleus increased LSNA, mean arterial pressure, and heart rate only after blockade of neuropeptide Y Y1 receptors. Therefore, we conclude that leptin increases LSNA in part via increased glutamatergic and α-melanocyte-stimulating hormone drive of paraventricular sympathoexcitatory neurons, the latter of which requires simultaneous withdrawal of tonic neuropeptide Y inhibition.

Original languageEnglish (US)
Pages (from-to)1034-1041
Number of pages8
JournalHypertension
Volume66
Issue number5
DOIs
StatePublished - Nov 1 2015

Fingerprint

Paraventricular Hypothalamic Nucleus
Leptin
Hypothalamus
Receptor, Melanocortin, Type 3
Receptor, Melanocortin, Type 4
Heart Rate
Arterial Pressure
Arcuate Nucleus of Hypothalamus
Neuropeptide Y
Injections
Kynurenic Acid
Melanocyte-Stimulating Hormones
Ionotropic Glutamate Receptors
Muscimol
Baroreflex
Sprague Dawley Rats
Glutamic Acid
Neurons

Keywords

  • arcuate nucleus
  • arterial pressure
  • baroreflex
  • BIBO 3304
  • kynurenate
  • SHU9119

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Role of the paraventricular nucleus of the hypothalamus in the sympathoexcitatory effects of leptin. / Shi, Zhigang; Li, Baoxin; Brooks, Virginia.

In: Hypertension, Vol. 66, No. 5, 01.11.2015, p. 1034-1041.

Research output: Contribution to journalArticle

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