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Highlights: [•] hcrt-1 and NE axons have overlapping distributions in BST. [•] Glu stimulation of BST elicits decreases in MAP and HR. [•] Injections of hcrt-1/NE in BST attenuate decreases in MAP and HR elicited by Glu. [•] α2-AR and GABAA receptor antagonists attenuated the hcrt-1/NE inhibition of Glu responses. [•] hcrt-1 involved in the release of NE that acts at α2-AR effecting GABA neurons. [Copyright &y& Elsevier]

Highlights: [•] Acute IH reduced body weight, food intake and active cycle locomotion without altering adipose tissue mass. [•] Adipose tissue leptin protein was reduced while adiponectin protein was elevated after acute IH. [•] Plasma leptin was increased while adiponectin decreased after acute IH. [•] pSTAT3 and POMC expression were elevated in arcuate nucleus and pERK1/2 reduced after acute IH. [ABSTRACT FROM AUTHOR]

Highlights: [•] Lateral hypothalamic hcrt-1 neurons co-express L-Enk. [•] Hcrt-1/L-Enk neurons innervate caudal NTS. [•] Injections of hcrt-1 and DADL into NTS elicit depressor and bradycardia responses. [•] DADL potentiates hcrt-1 cardiovascular responses. [•] δ- and μ-opioid receptors may be involved in mediating hcrt-1 cardiovascular responses. [ABSTRACT FROM AUTHOR]

Abstract: Glomus cells in the carotid body are responsible for detecting changes in the partial pressure of blood oxygen (PO2). These glomus cells have recently been found to express leptin receptors and are activated by intermittent hypoxia (IH) and systemic leptin injections, although the function of leptin within the carotid body remains unknown. The present study was done to investigate whether IH activates leptin signalling pathways within leptin-expressing carotid body glomus cells. Rats were subjected to IH (120-s normoxia, 80-s hypoxia for 8h) or normoxia (8h). Exposure to IH increased plasma leptin levels almost sixfold compared to normoxic controls. Additionally, IH was found to increase leptin, ERK1/2 and Fra-1/2 immunoreactivity within glomus cells. Systemic leptin injections evoked similar effects on leptin, ERK1/2 and Fra-1/2 immunoreactivity within the glomus cells. Furthermore, using Western blot analysis, IH was found to increase protein expression of leptin, the short form of the leptin receptor (Ob-R100 kDa) and suppressor of cytokine signalling 3. On the other hand, IH induced a decrease in long form of leptin receptors (Ob-Rb) protein expression. Taken together, these data suggest that the increased levels of leptin within the circulation and those within the glomus cells induced by IH may alter carotid bodies chemosensitivity to hypoxic stimuli. [Copyright &y& Elsevier]

Abstract: Leptin microinjections into the nucleus of the solitary tract (NTS) have been shown to elicit sympathoexcitatory responses, and potentiate the cardiovascular responses to activation of the chemoreflex. In this study, experiments were done in Sprague–Dawley rats initially to provide a detailed mapping within the NTS complex of cells containing immunoreactivity to the long form of the leptin receptor (Ob-Rb). In a second series, this NTS region containing Ob-Rb immunoreactive cells was explored for single units antidromically activated by stimulation of pressor sites in the rostral ventrolateral medulla (RVLM). These antidromically identified neurons were then tested for their response to intra-carotid injections of leptin (50–100ng/0.1ml), and to activation of peripheral chemoreceptors following an injection of potassium cyanide (KCN) (80μg/0.1ml) into the carotid artery. Cells containing Ob-Rb-like immunoreactivity were found predominantly in the caudal NTS: within the medial, commissural and gelatinous (sub-postremal area) subnuclei of the NTS complex. Of 73 single units tested in these NTS regions, 48 were antidromically activated by stimulation of RVLM pressor sites and 25 of these single units responded with an increase in discharge rate after intra-carotid injections of leptin. In addition, 17 of these leptin responsive neurons were excited by the intra-carotid injections of KCN (80μg/0.1ml). Furthermore, the excitatory response of these single units to KCN was potentiated (59–83%) immediately following the leptin injection. These data indicate that leptin responsive neurons in NTS mediate chemoreceptor afferent information to pressor sites in the RVLM, and suggest that leptin may act as a facilitator on neuronal circuits within the NTS that potentiates the sympathoexcitatory responses elicited during the reflex activation of arterial chemoreceptors. [Copyright &y& Elsevier]

Abstract: Receptors for the calcium-regulating glycoprotein hormone stanniocalcin-1 (STC-1) have been found within the CNS and whether these receptors exist within the nucleus of the solitary tract (NTS), and their possible role in the regulation of arterial pressure (AP) is unknown. Experiments were done in the rat to: (1) map the distribution of STC-1 receptors throughout NTS using in situ ligand binding that uses a stanniocalcin-alkaline phosphatase (STC-AP) fusion protein; (2) determine whether protein and gene expression for STC-1 exists within NTS using immunohistochemistry, Western blot and real time qPCR; (3) determine the effect of microinjection of STC-1 into NTS on AP and the baroreflex. Cells exhibiting STC-1 binding sites were found mainly within the caudal medial (Sm), gelantinous and commissural subnuclei of NTS. Cells containing STC-1 immunoreactivity were found to overlap those regions of NTS that contained STC-1 receptors. STC-1 protein and gene expression were also found within caudal NTS. In chloralose-urethane–anesthetized rats, microinjections of STC-1 (1.76–176 nM; 20 nl) into the caudal Sm elicited a dose-related decrease in AP. In contrast, injections of a nonbioactive form of STC-1 (STC-1+guanosine 5′-triphosphate [GTP]), the vehicle (0.9% saline), or GTP alone did not elicit cardiovascular responses. Additionally, injection of STC-1 into Sm potentiated the AP responses to electrical stimulation of the ipsilateral aortic depressor nerve. Finally, bilateral injection of STC-1 primary antiserum (1:1000; 100 nl) into Sm elicited a long lasting increase in AP, whereas microinjection of heat inactivated STC-1 antiserum did not alter AP. Taken together these data suggest that endogenous STC-1 signaling in NTS is involved in regulating the excitability of neurons that normally function as components of the baroreceptor reflex controlling AP. [Copyright &y& Elsevier]

Angiotensin II (ANG II) is known to promote leptin production and secretion. Although ANG II type 1 receptors (AT 1 Rs) and leptin are expressed within the carotid body, it is not known whether AT 1 R and leptin are co-expressed in the same glomus cells nor if these peptides are affected within the carotid body by intermittent hypoxia (IH). This study was done to investigate whether ANG II modulated leptin signaling in the carotid body during IH. Rats were treated with captopril (Capt) or the AT 1 R blocker losartan (Los) in the drinking water for 3 days prior to being exposed to IH (8h) or normoxia (8h). IH induced increases in plasma ANG II and leptin compared to normoxic controls. Capt treatment abolished the plasma leptin changes to IH, whereas Los treatment had no effect on the IH induced increase in plasma leptin. Additionally, carotid body glomus cells containing both leptin and the long form of the leptin receptor (OB-Rb) were found to co-express AT 1 R protein, and IH increased the expression of only AT 1 R protein within the carotid body in both Capt- and non-Capt-treated animals. On the other hand, Los treatment did not modify AT 1 R protein expression to IH. Additionally, Capt and Los treatment eliminated the elevated carotid body leptin protein expression, and the changes in phosphorylated signal transducer and activator of transcription three protein, the short form of the leptin receptor (OB-R 100 ), suppressor of cytokine signaling 3, and phosphorylated extracellular-signal-regulated kinase 1/2 protein expression induced by IH. However, Capt elevated the expression of OB-Rb protein, whereas Los abolished the changes in OB-Rb protein to IH. These findings, taken together with the previous observation that ANG II modifies carotid body chemosensitivity, suggest that the increased circulating levels of ANG II and leptin induced by IH act at the carotid body to alter leptin signaling within the carotid body which in turn may influence chemoreceptor function. [ABSTRACT FROM AUTHOR]