Leptin impairs cardiovagal baroreflex function at the level of the solitary tract nucleus.
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 alpha 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.
Arnold
Amy C
AC
Hypertension and Vascular Research Center and Physiology and Pharmacology Department, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1032, USA.
Shaltout
Hossam A
HA
Gallagher
Patricia E
PE
Diz
Debra I
DI
D000704:Analysis of Variance; D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology*; D001919:Bradycardia / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D020738:Leptin / Q000009:adverse effects / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012016:Reference Values; D012680:Sensitivity and Specificity; D017552:Solitary Nucleus / Q000187:drug effects* / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
D020738:Leptin; D012333:RNA, Messenger