Nesfatin-1 acts on the hypothalamus and regulates the autonomic nervous system. However, the hypothalamic mechanisms of nesfatin-1 on the autonomic nervous system are not well understood. In this study, we found that intracerebroventricular (ICV) administration of nesfatin-1 increased the extracellular signal-regulated kinase (ERK) activity in rats. Furthermore, the activity of sympathetic nerves, in the kidneys, liver, and white adipose tissue (WAT), and blood pressure was stimulated by the ICV injection of nesfatin-1, and these effects were abolished owing to pharmacological inhibition of ERK. Renal sympathoexcitatory and hypertensive effects were also observed with nesfatin-1 microinjection into the paraventricular hypothalamic nucleus (PVN). Moreover, nesfatin-1 increased the number of phospho (p)-ERK1/2-positive neurons in the PVN and coexpression of the protein in neurons expressing corticotropin-releasing hormone (CRH). Pharmacological blockade of CRH signaling inhibited renal sympathetic and hypertensive responses to nesfatin-1. Finally, sympathetic stimulation of WAT and increased p-ERK1/2 levels in response to nesfatin-1 were preserved in obese animals such as rats that were fed a high-fat diet and leptin receptor-deficient Zucker fatty rats. These findings indicate that nesfatin-1 regulates the autonomic nervous system through ERK signaling in PVN-CRH neurons to maintain cardiovascular function and that the antiobesity effect of nesfatin-1 is mediated by hypothalamic ERK-dependent sympathoexcitation in obese animals.Nesfatin-1 is an 82-amino acid neuropeptide produced in the hypothalamus that acts on the brain to suppress appetite (1-6), increase energy expenditure (7), and induce cardiovascular changes, leading to body weight reduction (1), blood pressure (BP) elevation (8-10), and increased insulin sensitivity (11) in animals. Intracerebroventricular (ICV) administration of nesfatin-1 reduces food intake and body weight gain and elevates BP, heart rate (HR) (8), and peripheral glucose uptake (11). Thus, central nesfatin-1 may regulate the function of peripheral organs through neural activity to maintain homeostasis and regulate a number of physiological processes.Regarding the neural mechanism of physiological regulation by nesfatin-1, our previous study demonstrated that sympathetic nervous supply to the kidneys in anesthetized rats could be stimulated by the ICV injection of nesfatin-1 (10), suggesting that the sympathetic nervous system mediates the action of nesfatin-1. Recently, it has been reported that increased sympathetic stimulation of white adipose tissue (WAT) and the liver resulted in lipolysis (12) and glucogenesis (13), respectively, with the intracerebral administration of leptin, a feeding regulator and sympathetic activator. Thus, central nesfatin-1 may modulate sympathetic nerve outflow to WAT and the liver and regulate lipid and glucose metabolism; however, there are no studies reporting the effect of ICV nesfatin-1 on the neural activity of sympathetic nerves to WAT and the live...

The autonomic nervous system plays an important role in rat anaphylactic hypotension. It is well known that sympathetic nerve activity and cardiovascular function are affected by anesthetics. However, the effects of different types of anesthesia on the efferent renal sympathetic nerve activity (RSNA) during anaphylactic hypotension remain unknown. Therefore, we determined the renal sympathetic responses to anaphylactic hypotension in anesthetized and conscious rats and the roles of baroreceptors in these responses. Sprague-Dawley rats were randomly allocated to anesthetic groups that were given pentobarbital, urethane, or ketamine-xylazine and to a conscious group. The rats were sensitized using subcutaneously injected ovalbumin. The systemic arterial pressure (SAP), RSNA and heart rate (HR) were measured. The effects of sinoaortic baroreceptor denervation on RSNA during anaphylaxis were determined in pentobarbital-anesthetized and conscious rats. In all of the sensitized rats, the RSNA increased and SAP decreased after antigen injection. At the early phase within 35 min of the antigen injection, the antigen-induced sympathoexcitation in the conscious rats was significantly greater than that in the anesthetized rats. Anaphylactic hypotension was attenuated in the conscious rats compared to the anesthetized rats. The anesthetic-induced suppression of SAP and RSNA was greater in the order ketamine-xylazine >urethane = pentobarbital. Indeed, in the rats treated with ketamine-xylazine, RSNA did not increase until 40 min, and SAP remained at low levels after the antigen injection. The baroreceptor reflex, as evaluated by increases in RSNA and HR in response to the decrease in SAP induced by sodium nitroprusside (SNP), was suppressed in the anesthetized rats compared with the conscious rats. Consistent with this finding, baroreceptor denervation attenuated the excitatory responses of RSNA to anaphylaxis in the conscious rats but not in the pentobarbital-anesthetized rats. RSNA was increased markedly in conscious rats during anaphylactic hypotension. Anesthetics attenuated this antigen-induced renal sympathoexcitation through the suppression of baroreceptor function.

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Wang M, Tanida M, Shibamoto T, Kurata Y. Alpha-adrenoceptor antagonists and chemical sympathectomy exacerbate anaphylaxis-induced hypotension, but not portal hypertension, in anesthetized rats. Am J Physiol Regul Integr Comp Physiol 305: R900 -R907, 2013. First published August 15, 2013; doi:10.1152/ajpregu.00120.2013.-Anaphylactic shock is sometimes life-threatening, and it is accompanied by hepatic venoconstriction in animals, which, in part, accounts for anaphylactic hypotension. Roles of norepinephrine and ␣-adrenoceptor in anaphylaxis-induced hypotension and portal hypertension were investigated in anesthetized ovalbumin-sensitized Sprague-Dawley rats. The sensitized rats were randomly allocated to the following pretreatment groups (n ϭ 6/group): 1) control (nonpretreatment), 2) ␣ 1-adrenoceptor antagonist prazosin, 3) nonselective ␣-adrenoceptor antagonist phentolamine, 4) 6-hydroxydopamine-induced chemical sympathectomy, and 5) surgical hepatic sympathectomy. Anaphylactic shock was induced by an intravenous injection of the antigen. The systemic arterial pressure (SAP), central venous pressure (CVP), portal venous pressure (PVP), and portal venous blood flow (PBF) were measured, and splanchnic [Rspl: (SAPϪ PVP)/PBF] and portal venous [Rpv: (PVPϪCVP)/PBF] resistances were determined. Separately, we measured efferent hepatic sympathetic nerve activity during anaphylaxis. In the control group, SAP markedly decreased, followed by a gradual recovery toward baseline. PVP and Rpv increased 3.2-and 23.3-fold, respectively, after antigen. Rspl decreased immediately, but only transiently, after antigen, and then increased 1.5-fold later than 10 min. The ␣-adrenoceptor antagonist pretreatment or chemical sympathectomy inhibited the late increase in Rspl and the SAP recovery. Pretreatment with ␣-adrenoceptor antagonists, or either chemical or surgical hepatic sympathectomy, did not affect the antigeninduced increase in Rpv. Hepatic sympathetic nerve activity did not significantly change after antigen. In conclusion, ␣-adrenoceptor antagonists and chemical sympathectomy exacerbate anaphylaxis-induced hypotension, but not portal hypertension, in anesthetized rats. Hepatic sympathetic nerves are not involved in anaphylactic portal hypertension. anaphylactic shock; portal hypertension; hepatic sympathetic nerve activity; chemical sympathectomy; prazosin; phentolamine; hepatic venoconstriction ANAPHYLACTIC SHOCK IS A SERIOUS allergic reaction and is potentially life threatening (2). Decreases in blood pressure during circulatory shock, such as acute hemorrhage, reduce afferent impulses from arterial baroreceptors, thereby activating the sympathetic nervous system (14). The sympathoexcitation, as evidenced by increased renal sympathetic nerve activity (20) or circulating catecholamine levels (32), was also reported during anaphylaxis. However, the roles of norepinephrine released from the sympathetic nerve terminals in anaphylactic shock have not been determined, although those of ␤-adrenoceptors and epinephrine released f...

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During hypovolemic shock, skeletal muscle blood flow could be redistributed to vital organs via vasoconstriction in part evoked by activation of the innervating sympathetic nerve activity. However, it is not well known whether this mechanism operates during anaphylactic shock. We determined the femoral artery blood flow (FBF) and lumbar sympathetic nerve activity (LSNA) mainly regulating the hindquater muscle blood flow during anaphylactic hypotension in anesthetized rats. Anesthetized Sprague-Dawley rats were randomly allocated to the following groups (n = 7/group): (1) non-sensitized, (2) anaphylaxis, (3) anaphylaxis-lumbar sympathectomy (LS) and (4) anaphylaxis-sinoaortic denervation (SAD) groups. Anaphylaxis was induced by an intravenous injection of the ovalbumin antigen to the sensitized rats. The systemic arterial pressure (SAP), heart rate (HR), central venous pressure (CVP), FBF and LSNA were continuously measured. In the anaphylaxis group, LSNA and HR increased, while SAP and FBF decreased after antigen injection. In the anaphylaxis-SAD group, LSNA did not significantly change during the early phase, but the responses of SAP and FBF were similar to those in the anaphylaxis group. In the anaphylaxis-LS group, both FBF and SAP decreased similarly to the anaphylaxis group during anaphylactic hypotension. These results indicated that LSNA increased via baroreceptor reflex, but this sympathoexcitation or LS did not affect antigen-induced decreases in FBF or SAP. Lumbar sympathetic nerves are not involved in regulation of the blood flow to the hindlimb or systemic blood pressure during anaphylactic hypotension in anesthetized rats.

(Cardiol J 2014; 21, 1: 11-17)

We investigated the effects of perioperative blood transfusion in the prognosis of hereditary and sporadic colon cancer. There are 1075 colon cancer patients, including 936 sporadic colon cancer and 139 with hereditary colon cancer undergoing surgery at our hospital. All patients underwent 10 years of follow-up. In the sporadic group, mortality, local recurrence rate and distant metastases rate of transfused patients were significantly higher than non-transfused patients. The 10-year survival rates were significantly lower in patients receiving blood transfusions compared to non-transfused patients. In the hereditary group, mortality was higher in transfused patients compared to non-transfused patients.