title: The influence of angiotensin-(1-7) peptidomimetic (AVE 0991) and nebivolol on angiotensin I metabolism in aorta of apoE-knockout mice.
abstract: The detrimental role of over activation of renin-angiotensin system (RAS) in atherogenesis is widely recognized. Recently, we have demonstrated that Ang-(1-7) peptidomimetic - AVE0991, as well as known beta-adrenolytic agent nebivolol, exert anti-atherogenic actions in mouse model of atherosclerosis - apoE-knockout mice. Here, using LC-ESI-MS ex vivo system, we tested whether prolonged treatment of apoE-knockout mice by these drugs can influence RAS in aorta of apoE-knockout mice in regard to generation of most active metabolites of Ang I-Ang II and Ang-(1-7). As compared to wild type animals there was increased generation of Ang II in aorta of apoE-knockout mice, while the formation of Ang-(1-7) did not differ between both groups. Either treatment with AVE0991 or nebivolol resulted in significant attenuation of Ang II production in aorta of apoE-knockout mice. In conclusion, for the first time we directly demonstrated that there is increase in ability of aortic tissue to generate Ang II in mouse model of atherosclerosis of apoE knockout mice, and that such effect could be efficiently attenuated either by treatment of nebivolol or Ang-(1-7) peptidomimetic - AVE0991. The exact mechanism(s) responsible for interference of both drugs with RAS require further investigation.
authors: Chair of Pharmacology, Jagiellonian University Medical College, Cracow, Poland. mfolszan@cyf-kr.edu.pl
authors: R
authors: R
authors: Olszanecki
authors: M
authors: M
authors: Suski
authors: A
authors: A
authors: Gebska
authors: J
authors: J
authors: Toton-Zuranska
authors: K
authors: K
authors: Kus
authors: J
authors: J
authors: Madej
authors: B
authors: B
authors: Bujak-Gizycka
authors: J
authors: J
authors: Jawien
authors: R
authors: R
authors: Korbut
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000627:therapeutic use*; D000803:Angiotensin I / Q000819:agonists / Q000737:chemistry / Q000378:metabolism; D000804:Angiotensin II / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism; D001578:Benzopyrans / Q000627:therapeutic use*; D015536:Down-Regulation / Q000187:drug effects; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000627:therapeutic use*; D005260:Female; D007093:Imidazoles / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000068577:Nebivolol; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: C469726:AVE 0991; D058671:Adrenergic beta-1 Receptor Antagonists; D000959:Antihypertensive Agents; D001057:Apolipoproteins E; D001578:Benzopyrans; D004983:Ethanolamines; D007093:Imidazoles; D010446:Peptide Fragments; D014665:Vasodilator Agents; C506331:angiotensin I (1-9); D000068577:Nebivolol; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)