title: Effect of chronic central endothelin-1 on hemodynamics and plasma vasopressin in conscious rats.
abstract: OBJECTIVE
  These studies were designed to test whether chronic central administration of endothelin-1 induces changes in systemic hemodynamics and plasma vasopressin similar to those observed with acute microinjections of endothelin-1.
  
  
  METHODS
  Sprague Dawley rats underwent sham denervation or sinoaortic denervation. Three days later, baseline mean arterial blood pressure, heart rate, and vasopressin were assessed in conscious rats. Then, a cannula was stereotaxically inserted into the lateral ventricle and attached to an osmotic minipump that delivered one of the following: (i) artificial cerebrospinal fluid; (ii) endothelin-1, 10 pmol/hour; (iii) BQ-123, 400 pmol/hour; or (iv) endothelin-1+BQ-123. Mean arterial blood pressure and heart rate were monitored daily and blood was obtained for plasma vasopressin on days 3 and 9. On day 10, the rats were euthanized, the hypothalami were removed, and vasopressin messenger ribonucleic acid content was assessed.
  
  
  RESULTS
  The pressor effect of intracerebroventricular endothelin-1 was similar in intact and sinoaortic denervation rats and was prevented by endothelin receptor A antagonism with BQ-123. Administration of BQ-123 alone resulted in a depressor and bradycardia in sinoaortically denervated rats. Chronic endothelin-1 administration did not change plasma vasopressin but resulted in a significant decrease in hypothalamic vasopressin messenger ribonucleic acid levels, which was reversed by endothelin receptor A inhibition.
  
  
  CONCLUSIONS
  Although the pressor effect of chronic central endothelin-1 is similar to that reported with acute endothelin-1, plasma vasopressin levels do not increase, at least in part, due to downregulation of hypothalamic vasopressin gene expression. Sinoaortic denervation increases endogenous central endothelin receptor A tone. Furthermore, these observations confirm that the pressor effect of central endothelin-1 is not mediated by plasma vasopressin.
authors.affiliation: Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA. nrossi@med.wayne.edu
authors.forename: Noreen F
authors.initials: NF
authors.lastname: Rossi
authors.forename: Fong
authors.initials: F
authors.lastname: Zhang
authors.forename: Haiping
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003243:Consciousness / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D019332:Endothelin-1 / Q000494:pharmacology* / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D007031:Hypothalamus / Q000098:blood supply / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014667:Vasopressins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics
chemical_list: D019332:Endothelin-1; D014667:Vasopressins