title: Age-specific influences of chronic administration of the fatty acid amide hydrolase inhibitor URB597 on cardiovascular parameters and organ hypertrophy in DOCA-salt hypertensive rats.
abstract: BACKGROUND
  The endocannabinoid system has been suggested to be up-regulated in hypertension. Fatty acid amide hydrolase (FAAH) is the main hydrolytic enzyme for the encocannabinoid anandamide. The aim of our study was to examine the age-specific influence of the chronic administration of the FAAH inhibitor URB597 on blood pressure (BP), heart rate (HR) and cardiac and renal hypertrophy in hypertensive rats during two critical periods for the development of hypertension.
  
  
  METHODS
  Experiments were performed on uninephrectomised 4 (younger) and 6-7 (older) weeks old rats rendered hypertensive by a high salt diet and deoxycorticosterone acetate (DOCA) injections and on normotensive animals (unilateral nephrectomy only). URB597 1mg/kg or its vehicle were injected twice daily for 2 weeks.
  
  
  RESULTS
  The DOCA-salt procedure caused comparable increases in BP (but not HR) in both age groups and more strongly increased cardiac and renal hypertrophic indices in younger than in older animals. Chronic URB597 administration reduced BP and HR in older but not in younger rats. In contrast, the inhibitor diminished the cardiac and renal hypertrophy in younger but not in older animals. URB597 did not affect body weight gain, and food and water intake in normotensive or hypertensive rats.
  
  
  CONCLUSIONS
  Two weeks of URB597 administration to DOCA-salt hypertensive rats caused an age-specific reduction in BP, HR and cardiac and renal hypertrophy and did not affect the body weight, and water and food intake. Thus, caution should be taken during studies of FAAH inhibitors because of their potential age-specific effects.
authors.affiliation: Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Białystok, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Toczek
authors.affiliation: Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Białystok, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Baranowska-Kuczko
authors.affiliation: Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Białystok, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Grzęda
authors.affiliation: Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Białystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Pędzińska-Betiuk
authors.affiliation: Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Białystok, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Weresa
authors.affiliation: Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Białystok, Poland. Electronic address: bmalin@umb.edu.pl.
authors.forename: Barbara
authors.initials: B
authors.lastname: Malinowska
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D002219:Carbamates / Q000008:administration & dosage*; D064791:Desoxycorticosterone Acetate / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy*; D006984:Hypertrophy / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001549:Benzamides; D002219:Carbamates; D064791:Desoxycorticosterone Acetate; D000099252:Fatty Acid Amide Hydrolases; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester
keywords: Age-specific; Anandamide; DOCA-salt hypertension; Endocannabinoid system; URB597