title: Effect of nebivolol treatment during pregnancy on the genital circulation, fetal growth and postnatal development in the Wistar rat.
abstract: The aim of study was to evaluate the effects of nebivolol, a cardioselective beta-1 adrenergic receptor blocker of the third generation with vasodilatory properties, vs. bisoprolol on the genital circulation, uterine vasculature, fetal growth and postnatal development in pregnant Wistar rats. Non invasive measurements of systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR), and invasive measurement of genital blood flow (GBF) were taken in pregnant rats, by tail cuff and transonic probe methods respectively, after an oral treatment by gastric gavage with nebivolol (8mg/kg/day) or bisoprolol (10mg/kg/day) from day 11 to day 18 of pregnancy. Other morphometrical and histological measurements were performed on the ovarian and uterine arteries to evaluate the effect of nebivolol on the uterine vasculature. Furthermore, postnatal mortality and pup growth were recorded. The data demonstrated that nebivolol (compared with bisoprolol) induced a significant decrease in SBP, HR and GBF while DBP remained unchanged. Moreover, nebivolol increased the diameter and the length of ovarian and uterine arteries and the number of uterine artery segmental branches. The results also showed that the body weight gain of newborns in the nebivolol group was significantly lower vs. bisoprolol and vs. control with a higher mortality rate. The nebivolol action is not only limited to its favorable hemodynamic effects represented by a decrease in blood pressure, but it also produces adverse effects on fetal growth and postnatal development that may limit its therapeutic use in females during pregnancy.
authors: LUNAM Université, Oniris, UPSP 5304 de Physiopathologie Animale et Pharmacologie Fonctionnelle, Atlanpole La Chantrerie, BP 40706, Nantes F-44307, France.
authors: Kassem
authors: K
authors: Altoama
authors: LUNAM Université, Oniris, UPSP 5304 de Physiopathologie Animale et Pharmacologie Fonctionnelle, Atlanpole La Chantrerie, BP 40706, Nantes F-44307, France.
authors: Mohamed
authors: M
authors: Yassine Mallem
authors: LUNAM Université, Oniris, UPSP 5304 de Physiopathologie Animale et Pharmacologie Fonctionnelle, Atlanpole La Chantrerie, BP 40706, Nantes F-44307, France.
authors: Chantal
authors: C
authors: Thorin
authors: 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.
authors: Eric
authors: E
authors: Betti
authors: 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.
authors: Jean-Claude
authors: JC
authors: Desfontis
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D017298:Bisoprolol / Q000009:adverse effects / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects* / Q000502:physiology; D005835:Genitalia / Q000098:blood supply*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D000068577:Nebivolol / Q000009:adverse effects* / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects* / Q000502:physiology; D014599:Uterus / Q000098:blood supply / Q000187:drug effects
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D000068577:Nebivolol; D017298:Bisoprolol
keywords: Antihypertensive; Fetal growth; Genital circulation; Mortality; Nebivolol; Pregnancy