Angiotensin receptor blockade in juvenile male rat offspring: Implications for long-term cardio-renal health
Autor: | Helena C. Parkington, Marianne Tare, Sarah L. Walton, Marc Q. Mazzuca, Karen M. Moritz, Mary E. Wlodek, Linda A. Gallo |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty Angiotensin receptor Offspring Birth weight Renal function Blood Pressure 030204 cardiovascular system & hematology Kidney Rats Inbred WKY Losartan Renin-Angiotensin System 03 medical and health sciences 0302 clinical medicine Vascular Stiffness Pregnancy Internal medicine medicine Animals Birth Weight Pharmacology Fetal Growth Retardation business.industry Age Factors Fibrosis Mesenteric Arteries Femoral Artery 030104 developmental biology Endocrinology medicine.anatomical_structure Blood pressure Animals Newborn Hypertension Female business Angiotensin II Type 1 Receptor Blockers medicine.drug Artery |
Zdroj: | Pharmacological research. 134 |
ISSN: | 1096-1186 |
Popis: | Inhibition of the renin-angiotensin system in early postnatal life is a potential therapeutic approach to prevent long-term cardiovascular and kidney diseases in individuals born small. We determined the long-term effects of juvenile losartan treatment on cardiovascular and kidney function in control male rat offspring and those exposed to uteroplacental insufficiency and born small. Bilateral uterine vessel ligation (Restricted) or sham (Control) surgery was performed in late gestation in Wistar Kyoto rats. At weaning, male offspring were randomly assigned to receive losartan in their drinking water or drinking water alone from 5 to 8 weeks of age, and followed to 26 weeks of age. Systolic blood pressure and kidney function were assessed throughout the study. Pressure myography was used to assess passive mechanical wall properties in mesenteric and femoral arteries from 26-week-old offspring. Losartan treatment for three weeks lowered systolic blood pressure in both Control and Restricted groups but this difference was not sustained after the cessation of treatment. Losartan, irrespective of birth weight, mildly increased renal tubulointerstitial fibrosis when assessed at 26 weeks of age. Mesenteric artery stiffness was increased by the early losartan treatment, and was associated with increased collagen and decreased elastin content. Losartan also exerted long-term increases in fat mass and decreases in skeletal muscle mass. In this study, untreated Restricted offspring did not develop hypertension, vascular dysfunction or kidney changes as anticipated. Regardless, we demonstrate that short-term losartan treatment in the juvenile period negatively affects postnatal growth, and kidney and vascular parameters in adulthood, irrespective of birth weight. The long-term effects of early-life losartan treatment warrant further consideration in settings where the potential benefits may outweigh the risks; i.e. when programmed adulthood diseases are apparent and in childhood cardiovascular and kidney diseases. |
Databáze: | OpenAIRE |
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