Effect of nebivolol treatment during pregnancy on the intrauterine fetal growth, mortality and pup postnatal development in the l-NAME-induced hypertensive rats.
The present study was carried out to evaluate the effect of nebivolol vs. bisoprolol treatment on the intrauterine fetal growth, mortality and postnatal development in Nω-Nitro-l-arginine methyl ester hydrochloride (l-NAME)-induced hypertensive rats. Hypertension was induced in normotensive pregnant Wistar rats by daily administration of l-NAME (100mg/kg/day, in the drinking water) for the period of pregnancy. After 9 days of l-NAME treatment, rats with systolic and diastolic blood pressure (SBP and DBP) more than 140/90mmHg were considered hypertensive. Then, some of them were treated from day 11 to day 18 of pregnancy with nebivolol (8mg/kg/day) or bisoprolol (10mg/kg/day) via oral gavage. SBP, DBP and heart rate (HR) were re-evaluated by tail cuff method on day 19 of pregnancy and morphometrical or histological studies were performed on day 20. In addition, the mortality and postnatal development of newborn pups were assessed in all groups. The l-NAME administration during pregnancy induced an increase in SBP and DBP while HR did not change. Nebivolol or bisoprolol treatment completely prevented the elevation of SBP and DBP induced by l-NAME with a reduction in HR in pregnant and non-pregnant rats. The intra-uterine fetal growth and the postnatal development of newborn rats in nebivolol-treated hypertensive group were significantly lower vs. control and higher vs. bisoprolol-treated group with a higher mortality in the both types of treatments vs. control rats. The nebivolol and bisoprolol administration produce adverse effects on fetal growth and postnatal development, that limits their therapeutic use in females during pregnancy.
LUNAM Université, Oniris, «UPSP 5304 de Physiopathologie Animale et Pharmacologie Fonctionnelle», Atlanpole La Chantrerie, BP 40706, Nantes F-44307, France.
Kassem
K
Altoama
LUNAM Université, Oniris, «UPSP 5304 de Physiopathologie Animale et Pharmacologie Fonctionnelle», Atlanpole La Chantrerie, BP 40706, Nantes F-44307, France.
Mohamed Yassine
MY
Mallem
LUNAM Université, Oniris, «UPSP 5304 de Physiopathologie Animale et Pharmacologie Fonctionnelle», Atlanpole La Chantrerie, BP 40706, Nantes F-44307, France.
Chantal
C
Thorin
LUNAM Université, Oniris, «UPSP 5304 de Physiopathologie Animale et Pharmacologie Fonctionnelle», Atlanpole La Chantrerie, BP 40706, Nantes F-44307, France; LUNAM Université, Oniris, «Unité d'Anatomie comparée», Atlanpole La Chantrerie, BP 40706, Nantes F-44307, France.
Eric
E
Betti
LUNAM Université, Oniris, «UPSP 5304 de Physiopathologie Animale et Pharmacologie Fonctionnelle», Atlanpole La Chantrerie, BP 40706, Nantes F-44307, France. Electronic address: jean-claude.desfontis@oniris-nantes.fr.
Jean-Claude
JC
Desfontis
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D000068577:Nebivolol / Q000494:pharmacology* / Q000627:therapeutic use; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000098:blood supply / Q000187:drug effects
D000068577:Nebivolol; D019331:NG-Nitroarginine Methyl Ester
Fetal growth; Hypertension; Mortality; Nebivolol; Pregnancy; l-NAME