title: Hypertension study in anaesthetized rabbits: protocol proposal for AT1 antagonists screening.
abstract: BACKGROUND
  The aim of this study was to establish an optimized fast and safe protocol for the pharmacological screening of AT(1) antagonists.
  
  
  METHODS
  The pharmaceutical prototype AT(1) antagonist losartan, its active metabolite EXP3174 and the synthetic compound MMK1 were analysed in order to validate the protocol. Ang II was continuously infused while the animals received the drugs in two procedures.
  
  
  RESULTS
  In the post-treatment procedure drugs were administered either in a single bolus dose or in a sequential manner. When losartan was administered in a single bolus dose, efficacy was evident until the 7th min (p=0.012) whilst EXP3174 infusion extended the efficiency up to the end of the study (p=0.006). In addition, the sequential injections of losartan prolonged the inhibitory time interval until the end of the study (p=0.045). In the pre-treatment procedure, results suggested a dose-dependent inhibitory effect for both antagonists. The pressor response to Ang II was unchanged after MMK1 administration either in the post- or in the pre-treatment mode.
  
  
  CONCLUSIONS
  The proposed protocol appears to be safe, simple and fast for the pharmacological screening of AT(1) antagonists and enables the evaluation of new antagonists using lower doses than any other reported in the literature.
authors.affiliation: Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, Athens, Greece.
authors.forename: Aggeliki P
authors.initials: AP
authors.lastname: Politi
authors.forename: Maria V
authors.initials: MV
authors.lastname: Zervou
authors.forename: Helen
authors.initials: H
authors.lastname: Triantafyllidi
authors.forename: Panagiotis G
authors.initials: PG
authors.lastname: Zoumpoulakis
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Mavromoustakos
authors.forename: Anastasia A
authors.initials: AA
authors.lastname: Zoga
authors.forename: Panagiota
authors.initials: P
authors.lastname: Moutevelis-Minakakis
authors.forename: George
authors.initials: G
authors.lastname: Kokotos
authors.forename: Efstathios K
authors.initials: EK
authors.lastname: Iliodromitis
authors.forename: Dimitris Th
authors.initials: DT
authors.lastname: Kremastinos
mesh_terms: D000758:Anesthesia; D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D015203:Reproducibility of Results; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; C066026:losartan carboxylic acid; D019808:Losartan