Fetal and postnatal ovine mesenteric vascular reactivity

Area of Science:

• Fetal and neonatal physiology
• Vascular biology
• Gastrointestinal development

Background:

• Intestinal circulation and mesenteric arterial (MA) reactivity are crucial for fetal adaptation to enteral nutrition.
• MA vasoreactivity is hypothesized to change with gestation, with vasodilator pathways becoming dominant postnatally.

Purpose of the Study:

• To investigate the ontogenic changes in ovine mesenteric artery vasoreactivity.
• To determine the role of specific vasoconstrictor and vasodilator pathways in late-gestation and neonatal lambs.
• To explore the molecular mechanisms underlying these vascular changes.

Main Methods:

• Isolated small distal MA rings from fetal and postnatal lambs at various gestational ages.
• Assessed vasoreactivity to vasoconstrictors (norepinephrine, endothelin-1) and vasodilators (NO donors).
• Performed protein and mRNA assays for key receptors and enzymes (e.g., eNOS, sGC, PDE5).

Main Results:

• MA constriction peaked at 134 days gestation, while relaxation to vasodilators was maximal postnatally.
• Endothelial NO synthase (eNOS) activity was low at 134 days gestation.
• Expression of alpha-adrenergic receptor 1A (ADRA1A) increased significantly at 134 days and decreased postnatally; sGC and PDE5 protein levels increased from 134 to 141 days.

Conclusions:

• Mesenteric vasoconstriction predominates in late-preterm gestation (134 days), a period with high necrotizing enterocolitis (NEC) incidence.
• A shift towards vasodilatory influences occurs near full-term birth.
• Alterations in this developmental pathway, particularly preterm birth, may represent a risk factor for NEC.