Cyclic nucleotide-dependent relaxation in human umbilical vessels

Area of Science:

• Vascular pharmacology
• Physiology
• Neonatal medicine

Background:

• Umbilical vessels exhibit low sensitivity to dilation, a phenomenon with potential physiological significance.
• Understanding the relaxation mechanisms in human umbilical arteries (HUAs) and veins (HUVs) is crucial for perinatal physiology.

Purpose of the Study:

• To investigate the differential relaxation responses of HUAs and HUVs to agonists targeting cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) pathways.
• To elucidate the role of nitric oxide (NO) and adrenergic receptors in umbilical vessel relaxation.

Main Methods:

• Isometric force measurement using vascular rings from HUAs and HUVs in organ baths.
• Concentration-response curves were generated for various agonists including NO donors, guanylate cyclase stimulators, adenylate cyclase activators, beta-adrenergic receptor agonists, and phosphodiesterase inhibitors.
• Pharmacological inhibition of nitric oxide synthase (NOS), soluble guanylate cyclase (sGC), protein kinase A (PKA), and protein kinase G (PKG) was employed.

Main Results:

• Umbilical vessels demonstrated limited relaxation (<30%) to all tested agonists.
• Sodium nitroprusside (SNP), forskolin, phosphodiesterase (PDE) inhibitors, and beta-adrenergic receptor (ADRB) agonists induced similar relaxation in both HUAs and HUVs.
• BAY 41-2272 was more effective in relaxing HUVs than HUAs.
• ADRB agonist-induced relaxation was attenuated by endothelium removal or NOS/sGC inhibition, indicating partial mediation by the NO pathway.
• ADRB1 relaxation was impaired by PKA/PKG inhibition, ADRB2 by neither, and ADRB3 by PKG in HUAs and PKA in HUVs, despite weak ADRB3 expression.

Conclusions:

• Human umbilical arteries and veins possess a limited capacity for relaxation in term infants.
• The nitric oxide pathway is a significant contributor to beta-adrenergic receptor-mediated relaxation in umbilical vessels.
• Differential effects of PKA and PKG inhibitors on ADRB-mediated relaxation suggest complex signaling pathways in HUAs and HUVs.