Atrial natriuretic peptide enhances microvascular albumin permeability by the caveolae-mediated transcellular pathway

Abstract

AimsCardiac atrial natriuretic peptide (ANP) participates in the maintenance of arterial blood pressure and intravascular volume homeostasis. The hypovolaemic effects of ANP result from coordinated actions in the kidney and systemic microcirculation. Hence, ANP, via its guanylyl cyclase-A (GC-A) receptor and intracellular cyclic GMP as second messenger, stimulates endothelial albumin permeability. Ultimately, this leads to a shift of plasma fluid into interstitial pools. Here we studied the role of caveolae-mediated transendothelial albumin transport in the hyperpermeability effects of ANP.Methods and resultsIntravital microscopy studies of the mouse cremaster microcirculation showed that ANP stimulates the extravasation of fluorescent albumin from post-capillary venules and causes arteriolar vasodilatation. The hyperpermeability effect was prevented in mice with conditional, endothelial deletion of GC-A (EC GC-A KO) or with deleted caveolin-1 (cav-1), the caveolae scaffold protein. In contrast, the vasodilating effect was preserved. Concomitantly, the acute hypovolaemic action of ANP was abolished in EC GC-A KO and Cav-1−/− mice. In cultured microvascular rat fat pad and mouse lung endothelial cells, ANP stimulated uptake and transendothelial transport of fluorescent albumin without altering endothelial electrical resistance. The stimulatory effect on albumin uptake was prevented in GC-A- or cav-1-deficient pulmonary endothelia. Finally, preparation of caveolin-enriched lipid rafts from mouse lung and western blotting showed that GC-A and cGMP-dependent protein kinase I partly co-localize with Cav-1 in caveolae microdomains.ConclusionANP enhances transendothelial caveolae-mediated albumin transport via its GC-A receptor. This ANP-mediated cross-talk between the heart and the microcirculation is critically involved in the regulation of intravascular volume.

Hypoxic Trophoblast HMGB1 Induces Endothelial Cell Hyperpermeability via the TRL-4/Caveolin-1 Pathway

“…CAV-1 is the main structural component of endothelial caveolae and regulates endothelial transcytosis. Recent studies have shown that CAV-1 plays a key role in the regulation of microvascular endothelial and blood-retinal barrier permeability (42,53). Our results showed that CM from hypoxic trophoblast and HMGB1 increased endothelial cell monolayer permeability and increased CAV-1 protein expression at the same time.…”

“…The HUVECs/MAECs were treated with JEG-3 cells/PMTs CM for an additional 24 h. FITC-BSA uptake of HUVEC/MAECs was performed as previously described with minor modifications (42). FITC-BSA (SigmaAldrich; at a final concentration of 0.5 mg/ml) and Hoechst 33325 (SigmaAldrich; at a final concentration of 1 mg/ml) were added to the cells and incubated for 30 min.…”

Association between B-lines detected during lung ultrasound and various factors in hemodialysis patients

“…Among nondialysis patients, lung congestion was correlated with the NT-proBNP level [22]. Natriuretic peptides may directly enhance capillary permeability, an effect that may explain the association in addition to filling pressure alone [33]. In this study, we also showed a positive and independent relationship between the number of B-lines and the serum NT-proBNP level in hemodialysis patients.…”

Atrial natriuretic peptide and regulation of vascular function in hypertension and heart failure

“…Both ANP and BNP protected against thrombin-induced barrier dysfunction in the pulmonary microcirculation in a cGMPindependent manner, likely due reduced RhoA activation [22]. Most recently, ANP was shown to promote extravasation of fluorescent albumin from postcapillary venules and to cause arteriolar vasodilation in the mouse cremaster microcirculation [23]. The hyperpermeability effect was prevented in mice with conditional, endothelial deletion of NPR-A as well as in those with deleted caveolin-1, the caveolae scaffold protein.…”