title: Estrogen alters the bradycardia response to hypocretin-1 in the nucleus tractus solitarius of the ovariectomized female.
abstract: Experiments were performed to investigate the effect of 17beta-estradiol (E; 30 pg/ml plasma) treatment (15-25 days) in the ovariectomized (OVX) female Wistar rat on the cardiovascular responses to hypocretin-1 (hcrt-1) in the nucleus tractus solitarius (NTS). In an initial series of experiments, the distribution of hcrt-1-like immunoreactivity within the region of the NTS was mapped in both OVX only and OVX+E animals. Hcrt-1 immunoreactivity was found throughout the NTS region in both groups of females, predominantly within the caudal interstitial, commissural, medial and lateral subnuclei of the NTS. The relative density of hcrt-1 immunoreactivity in all NTS subnuclei was similar in both female groups. Microinjections of hcrt-1 (0.5-10 pmol) into the caudal lateral and medial subnuclei of the NTS complex of the alpha-chloralose of the urethane-anaesthetized E-treated OVX rat elicited a dose-related decrease in heart rate (HR). On the other hand, although a dose-response effect on arterial pressure was evident, significant arterial pressure responses were observed only at the higher dose of hcrt-1 (>2.5 pmol). In the OVX only female rat, microinjection of hcrt-1 into similar NTS sites elicited a bradycardia and depressor response only at the highest dose of hcrt-1, and these responses were significantly smaller in magnitude than those elicited in the OVX+E animal. In addition, in the OVX only animals, a few sites within the caudal commissural subnucleus of the NTS complex were found at which hcrt-1 elicited tachycardia and pressor responses. Finally, it was found that the reflex bradycardia to the activation of arterial baroreceptors as a result of increasing systemic arterial pressure with phenylephrine (2-4 microg/kg) was significantly potentiated in the OVX+E animals only. These data suggest that hcrt-1 in the NTS of the female activates a neuronal circuit that controls the circulation and that the circulating level of E alters the sensitivity of these cardiovascular circuits to hcrt-1.
authors.affiliation: Department of Physiology, Faculty of Medicine and Dentistry, Health Sciences Centre, University of Western Ontario, London, ON, Canada N6A 5C1.
authors.forename: Cleusa V R
authors.initials: CV
authors.lastname: de Oliveira
authors.forename: M Patricia
authors.initials: MP
authors.lastname: Rosas-Arellano
authors.forename: L Pastor
authors.initials: LP
authors.lastname: Solano-Flores
authors.forename: Tanja
authors.initials: T
authors.lastname: Babic
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Li
authors.forename: John
authors.initials: J
authors.lastname: Ciriello
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001919:Bradycardia / Q000139:chemically induced / Q000188:drug therapy*; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004958:Estradiol / Q000627:therapeutic use*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008845:Microinjections; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D000068797:Orexins; D010052:Ovariectomy / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D017552:Solitary Nucleus / Q000187:drug effects* / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D004958:Estradiol