Effects Of Orexin-a On Rat Blood Pressure And Plasma Adrenocorticotropic Hormone And Corticosterone Levels

BACKGROUND: The hypothalamus is considered as an important organ which plays a pivotal role in the integration of a variety of neuroendocrine and autonomic response via a number of neurotransmitters upon challenges from external or internal stressors. Orexins, which were isolated from the lateral hypothalamic area (LHA) and perifornical area, include the two highly homologous peptides, orexin-A and orexin-B, proteolytically derived from the same precursor protein. Simultaneously with the discovery of orexins, the endogenous receptors for the two ligands were also identified as orexin type 1 and 2 receptors (OX1Rs and OX2Rs, respectively), both of which are members of the family of seven transmembrane domain G protein-coupled receptors (GPCRs). The orexin-containing neurons, confined in the lateral hypothalamic and perifornical area, broadly project to multiple regions of the whole central nervous system, implying their important role in the cooperation and integration of various physiological functions, such as feeding, digestion, balance of energy metabolism, sleeping/wake cycle, drug addiction, and so on. These days, the projections of the orexin neurons to the paraventricular hypothalamic nucleus (PVN) and other autonomic and endocrine centers draw researchers' attention. Several lines of evidence support a role of the Orexin as modulators of the stress response. However, it is unknown whether orexin is involved in stress induced cardiovascular response via an increase in activity of pituitary-adrenal axis.OBJETIVE: In the present study we examined the effects of icv administrated orexin-A on the tail arterial systolic blood pressure (TBP) and pituitary-adreanl axis of rats subjected stress stimulation.METERIALS AND METHODS: Ten Sprague-Dawley rats were randomly divided into two groups and implanted with a chronic indwelling cannula under sterile surgery. After ten days of recovery, one group were icv adminstrated 10μg orexin-A disolved in 5μl sterile saline and the other 5μl sterile saline as control. TBP were measured by a tail-cuff sphygmonometer 10 minutes before icv injection and in the following 30 minutes after icv injection, following which rats were immediately killed by decapitation and trunk blood was collected and centrifuged at 4℃. Supernatant plasma was collected and stored at -80℃. The concentration of plasma adrenocorticotropic hormone (ACTH) and corticosterone was determined by enzyme-linked immunosorbant assay (ELISA).RESULTS: 1. Compared with the values (117±2. 5mmHg) of TBP 10 minutes before icv injection, orexin-A significantly increased rat TBP and the values at 10, 20 and 30 minutes after icv injection were 136±6.1mmHg,134±5.3mmHg和130±3.4mmHg (P<0.01) , respectively. 2. Compared with rats administrated with rats, orexin-A significantly increased plasma adrenocorticotropic hormone (ACTH) (P <0.01) and gluococorticosterone (P <0.01) concerntration.CONCLUSIONS: Centrally administrated orexin-A increases rat TBP and the levels of plasma ACTH and corticosterone.