title: Enalapril and losartan restored blood pressure and vascular reactivity in intrauterine undernourished rats.
abstract: Epidemiological studies suggest that intrauterine undernutrition plays an important role in the development of arterial hypertension and endothelial dysfunction in adulthood. We have evaluated the effect of the Renin Angiotensin System inhibition on the blood pressure and the mesenteric arteriolar reactivity of the intrauterine undernourished rats. Wistar rats were fed either normal or 50% of the normal intake diets, during the whole gestational period. In this study only the male offspring was used. At 16 weeks of age, the rats were used for the study of blood pressure, microvascular reactivity studied in vivo-in situ to Angiotensin II (Ang II), Bradykinin (Bk) and Acetylcholine (Ach) before and after either losartan (10 mg/kg/15 days) or enalapril (15 mg/kg/21 days) treatment. We also evaluated the mesenteric and plasmatic Angiotensin Converting Enzyme (ACE), renal function, lipid plasmatic content, and insulin and glucose metabolism. Intrauterine undernutrition induced hypertension and increased response of mesenteric arterioles to Ang II and decreased vasodilation to Bk and Ach. The treatments with losartan or enalapril normalized the blood pressure levels and significantly improved the arteriolar responses to Bk, Ach and reduced the response to Ang II. No differences have been detected to ACE activity, renal function, lipid content and insulin and glucose metabolism. This study shows for the first time that Renin Angiotensin System inhibitors can normalize the cardiovascular alterations induced by intrauterine undernutrition.
authors.affiliation: Laboratory of Hypertension, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Ave Prof Lineu Prestes, São Paulo, SP, Brazil.
authors.forename: Graziela S
authors.initials: GS
authors.lastname: Ceravolo
authors.forename: Maria C P
authors.initials: MC
authors.lastname: Franco
authors.forename: Marcela S
authors.initials: MS
authors.lastname: Carneiro-Ramos
authors.forename: Maria L M
authors.initials: ML
authors.lastname: Barreto-Chaves
authors.forename: Rita C A
authors.initials: RC
authors.lastname: Tostes
authors.forename: Dorothy
authors.initials: D
authors.lastname: Nigro
authors.forename: Zuleica B
authors.initials: ZB
authors.lastname: Fortes
authors.forename: Maria Helena C
authors.initials: MH
authors.lastname: Carvalho
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects*; D004336:Drug Antagonism; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology; D005508:Food Deprivation; D007328:Insulin; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D044342:Malnutrition / Q000503:physiopathology*; D008643:Mesentery / Q000098:blood supply; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D001786:Blood Glucose; D007328:Insulin; D014665:Vasodilator Agents; D004656:Enalapril; D019808:Losartan