Atrial natriuretic peptide (ANP) regulates arterial blood pressure and volume. Its guanylyl cyclase-A (GC-A) receptor is expressed in vascular endothelium and mediates increases in cGMP, but the functional relevance is controversial. The present study aimed to characterize the endothelial effects of ANP in vivo and in vitro.

METHODS: 

We studied the effect of ANP on microvascular permeability to fluorescein isothiocyanate (FITC)-labeled albumin using intravital microscopy on the cremaster muscle of anesthetized mice. Permeability responses of cultured microvascular rat fat pad endothelial cells (RFPEC) were assessed by measurements of transendothelial electrical resistance using the electrical impedance system (ECIS) and of FITC-albumin transport across monolayers seeded on transwell filters.

RESULTS and CONCLUSION: 

Synthetic ANP administered retroorbitally as a single bolus injection (26 mg/kg BW) mildly but significantly increased the extravasation of FITC-albumin from postcapillary venules of the mouse cremaster muscle. These microvascular permeability responses were accompanied by acute decreases of systemic arterial blood pressure (on average by ~20 mmHg). In cultured RFPEC ANP increased intracellular cyclic GMP levels and stimulated transcellular FITC-albumin flux. Notably, transendothelial electrical resistance was not altered by ANP, suggesting that paracellular junctions were unaffected. We conclude that ANP stimulates microvascular endothelial macromolecule permeability by a GC-A/cGMP-dependent mechanism, possibly by stimulation of transcellular (not paracellular) albumin transport. ANP/GC-A-mediated increases in endothelial permeability might be critically involved in the hypovolemic, hypotensive actions of ANP.

Supported by Sonderforschungsbereich 688.