Atriopeptin-induced increases in endothelial cell permeability are associated with elevated cGMP levels

Area of Science:

• Endothelial cell biology
• Cardiovascular physiology
• Molecular pharmacology

Background:

• Nonrenal capillary hyperfiltration is a complex physiological process.
• The role of specific signaling molecules in regulating capillary permeability is not fully understood.

Purpose of the Study:

• To investigate the mechanism by which atriopeptin (AP) III affects endothelial cell permeability.
• To determine the involvement of cyclic nucleotides, specifically cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP), in AP-induced hyperfiltration.

Main Methods:

• Cultured bovine pulmonary artery endothelial cell monolayers were used.
• Albumin transfer rate was measured to assess permeability.
• Intracellular cGMP and cAMP levels were quantified after incubation with AP III and AP I.
• The effects of a phosphodiesterase inhibitor (IBMX) and a cGMP analogue were also examined.

Main Results:

• AP III significantly increased albumin transfer rate in a concentration-dependent manner.
• AP III elevated intracellular cGMP levels threefold.
• A phosphodiesterase inhibitor (IBMX) potentiated AP III-induced permeability and cGMP increase.
• AP I, a weaker agonist, did not significantly increase permeability.
• AP III did not alter intracellular cAMP levels.

Conclusions:

• AP III increases endothelial cell monolayer permeability associated with elevated cGMP levels.
• This suggests that increased cGMP may be a key mechanism in ANP-induced capillary hyperfiltration.