Leptin signaling in the nucleus of the solitary tract alters the cardiovascular responses to activation of the chemoreceptor reflex.
Circulating levels of leptin are elevated in individuals suffering from chronic intermittent hypoxia (CIH). Systemic and central administration of leptin elicits increases in sympathetic nervous activity (SNA), arterial pressure (AP), and heart rate (HR), and it attenuates the baroreceptor reflex, cardiovascular responses that are similar to those observed during CIH as a result of activation of chemoreceptors by the systemic hypoxia. Therefore, experiments were done in anesthetized Wistar rats to investigate the effects of leptin in nucleus of the solitary tract (NTS) on AP and HR responses, and renal SNA (RSNA) responses during activation of NTS neurons and the chemoreceptor reflex. Microinjection of leptin (5-100 ng; 20 nl) into caudal NTS pressor sites (l-glutamate; l-Glu; 0.25 M; 10 nl) elicited dose-related increases in AP, HR, and RSNA. Leptin microinjections (5 ng; 20 nl) into these sites potentiated the increase in AP and HR elicited by l-Glu. Additionally, bilateral injections of leptin (5 ng; 100 nl) into NTS potentiated the increase in AP and attenuated the bradycardia to systemic activation of the chemoreflex. In the Zucker obese rat, leptin injections into NTS neither elicited cardiovascular responses nor altered the cardiovascular responses to activation of the chemoreflex. Taken together, these data indicate that leptin exerts a modulatory effect on neuronal circuits within NTS that control cardiovascular responses elicited during the reflex activation of arterial chemoreceptors and suggest that increased AP and SNA observed in individuals with CIH may be due, in part, by leptin's effects on the chemoreflex at the level of NTS.
Dept. of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Univ. of Western Ontario, London, ON, Canada. john.ciriello@schulich.uwo.ca
John
J
Ciriello
Jason M
JM
Moreau
D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000008:administration & dosage / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D054411:Receptors, Leptin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D017552:Solitary Nucleus / Q000187:drug effects* / Q000502:physiology
D020738:Leptin; D054411:Receptors, Leptin; D018698:Glutamic Acid