title: Effect of angiotensin II type 1 (AT1) receptor antagonist on the endothelial dysfunction in spontaneously hypertensive rats in correlation with the nitric oxide system.
abstract: BACKGROUND
  Hypertension is associated with impaired endothelial function, which can be explained by a decrease in nitric oxide (NO) generation or by an enhanced inactivation of NO after its release from endothelial cells.
  
  
  OBJECTIVE
  The aim of this study was to investigate the effect of long-term treatment with losartan, an angiotensin II (AT1) receptor antagonist, on endothelial dysfunction in an animal model of hypertension in relation to the nitric oxide system.
  
  
  METHODS
  Losartan was administered to 48 sixteen-week-old spontaneously hypertensive rats, in a dose of 10 mg/kg bw/daily in drinking water, for 12 weeks. Systolic blood pressure (SBP) was measured at the beginning, after 4, 8 and 12 weeks of treatment, by the tail-cuff plethysmographic method. At each mentioned time point, a group of 12 animals was sacrificed and blood was withdrawn from the abdominal aorta. Plasma samples were used for determination of total nitrate/nitirite levels, cyclic guanosine monophosphate (cGMP) and endothelin (ET) 1 levels. Statistical evaluation of the results was performed by the use of a computer statistical programme Statistica for Windows 5.0.
  
  
  RESULTS
  Losartan produced a significant decrease of SBP at all time points. On the other hand, long-term treatment with this AT1 receptor antagonist produced a significant increase of nitrate/nitrite and cGMP plasma levels. When we compared the values of SBP with plasma nitrate/nitrite as well as with cGMP values, a statistically significant correlation was established. A statistically significant decrease in plasma endothelin 1 values was found during the whole study period. Also, a positive correlation between SBP and plasma endothelin 1 concentrations was observed.
  
  
  CONCLUSIONS
  Long-term losartan (AT1 receptor antagonist) treatment, apart from its blood pressure lowering effect in hypertension, has beneficial effects on the endothelial dysfunction which is at least partially due to the activation of the nitric oxide system. (Tab. 1, Fig. 2, Ref. 33.)
authors.affiliation: Department of Preclinical and Clinical Pharmacology and Toxicology, Medical Faculty, Skopje, Republic of Macedonia. majaslaninka@hotmail.com majaslaninka@hotmail.com
authors.forename: M
authors.initials: M
authors.lastname: Slaninka-Miceska
authors.forename: J
authors.initials: J
authors.lastname: Bogdanska
authors.forename: P
authors.initials: P
authors.lastname: Korneti
authors.forename: E
authors.initials: E
authors.lastname: Kostova
authors.forename: E
authors.initials: E
authors.lastname: Jovanoska
authors.forename: S
authors.initials: S
authors.lastname: Petrov
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology*; D009569:Nitric Oxide / Q000097:blood*; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D019332:Endothelin-1; D009569:Nitric Oxide; D006152:Cyclic GMP; D019808:Losartan