title: Inhibition of cyclooxygenase-2 reduces hypothalamic excitation in rats with adriamycin-induced heart failure.
abstract: BACKGROUND
  The paraventricular nucleus (PVN) of the hypothalamus plays an important role in the progression of heart failure (HF). We investigated whether cyclooxygenase-2 (COX-2) inhibition in the PVN attenuates the activities of sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in rats with adriamycin-induced heart failure.
  
  
  RESULTS
  Heart failure was induced by intraperitoneal injection of adriamycin over a period of 2 weeks (cumulative dose of 15 mg/kg). On day 19, rats received intragastric administration daily with either COX-2 inhibitor celecoxib (CLB) or normal saline. Treatment with CLB reduced mortality and attenuated both myocardial atrophy and pulmonary congestion in HF rats. Compared with the HF rats, ventricle to body weight (VW/BW) and lung to body weight (LW/BW) ratios, heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular peak systolic pressure (LVPSP) and maximum rate of change in left ventricular pressure (LV±dp/dtmax) were improved in HF+CLB rats. Angiotensin II (ANG II), norepinephrine (NE), COX-2 and glutamate (Glu) in the PVN were increased in HF rats. HF rats had higher levels of ANG II and NE in plasma, higher level of ANG II in myocardium, and lower levels of ANP in plasma and myocardium. Treatment with CLB attenuated these HF-induced changes. HF rats had more COX-2-positive neurons and more corticotropin releasing hormone (CRH) positive neurons in the PVN than did control rats. Treatment with CLB decreased COX-2-positive neurons and CRH positive neurons in the PVN of HF rats.
  
  
  CONCLUSIONS
  These results suggest that PVN COX-2 may be an intermediary step for PVN neuronal activation and excitatory neurotransmitter release, which further contributes to sympathoexcitation and RAS activation in adriamycin-induced heart failure. Treatment with COX-2 inhibitor attenuates sympathoexcitation and RAS activation in adriamycin-induced heart failure.
authors.affiliation: Department of Physiology, Shantou University Medical College, Shantou, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Kang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Wei-Jin
authors.initials: WJ
authors.lastname: Zang
authors.forename: Cui-Yu
authors.initials: CY
authors.lastname: Bao
authors.forename: Da-Nian
authors.initials: DN
authors.lastname: Qin
mesh_terms: D000804:Angiotensin II / Q000097:blood / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004317:Doxorubicin / Q000009:adverse effects; D006333:Heart Failure / Q000139:chemically induced / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D051381:Rats
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D018377:Neurotransmitter Agents; D000804:Angiotensin II; D004317:Doxorubicin; D009320:Atrial Natriuretic Factor; D003346:Corticotropin-Releasing Hormone; D051546:Cyclooxygenase 2; D009638:Norepinephrine