Leptin impairs cardiovagal baroreflex function at the level of the solitary tract nucleus

Amy Arnold, Hossam A. Shaltout, Patricia E. Gallagher, Debra I. Diz

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Circulating leptin is elevated in some forms of obesity-related hypertension, associated with impaired baroreflex function. Leptin receptors are present on vagal afferent fibers and neurons within the solitary tract nucleus, providing an anatomic distribution consistent with baroreflex modulation. Although solitary tract nucleus microinjection of 144 fmol/60 nL of leptin had no significant effect on baroreflex sensitivity for control of the heart rate in urethane/chloralose-anesthetized Sprague-Dawley rats, 500 fmol of leptin impaired baroreflex sensitivity for bradycardia in response to increases in pressure (1.15±0.04 versus 0.52±0.12 ms/mm Hg; P<0.01). Transgenic ASrAOGEN rats with low brain angiotensinogen have an upregulation of the leptin receptor and p85 α mRNA in the dorsal medulla relative to Sprague-Dawley rats. Consistent with these observations, the response to leptin was enhanced in ASrAOGEN rats, because both the 144-fmol (1.46±0.08 versus 0.75±0.10 ms/mm Hg; P<0.001) and 500-fmol (1.36±0.32 versus 0.44±0.06 ms/mm Hg; P<0.05) leptin microinjections impaired baroreflex sensitivity. At these doses, leptin microinjection had no effect on resting pressure, heart rate, or the tachycardic response to decreases in pressure in Sprague-Dawley or ASrAOGEN rats. Thus, exogenous leptin at sites within the solitary tract nucleus impairs the baroreflex sensitivity for bradycardia induced by increases in arterial pressure, consistent with a permissive role in mediating increases in arterial pressure. Baroreflex inhibition was enhanced in animals with evidence of increased leptin receptor and relevant signaling pathway mRNA.

Original languageEnglish (US)
Pages (from-to)1001-1008
Number of pages8
JournalHypertension
Volume54
Issue number5
DOIs
StatePublished - Nov 1 2009

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Solitary Nucleus
Baroreflex
Leptin
Leptin Receptors
Microinjections
Bradycardia
Pressure
Sprague Dawley Rats
Arterial Pressure
Heart Rate
Transgenic Rats
Afferent Neurons
Angiotensinogen
Messenger RNA
Chloralose
Urethane
Up-Regulation
Obesity
Hypertension
Brain

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Arnold, Amy ; Shaltout, Hossam A. ; Gallagher, Patricia E. ; Diz, Debra I. / Leptin impairs cardiovagal baroreflex function at the level of the solitary tract nucleus. In: Hypertension. 2009 ; Vol. 54, No. 5. pp. 1001-1008.
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Leptin impairs cardiovagal baroreflex function at the level of the solitary tract nucleus. / Arnold, Amy; Shaltout, Hossam A.; Gallagher, Patricia E.; Diz, Debra I.

In: Hypertension, Vol. 54, No. 5, 01.11.2009, p. 1001-1008.

Research output: Contribution to journalArticle

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