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Acta Physiologica 2012; Volume 204, Supplement 689
91st Annual Meeting of The German Physiological Society
3/22/2012-3/25/2012
Dresden, Germany
DUAL EFFECTS OF ATRIAL NATRIURETIC PEPTIDE ON SYSTEMIC MICROVASCULAR ENDOTHELIAL PERMEABILITY
Abstract number: P198
Chen1 *W., Oberwinkler1 H., Werner1 F., Gassner1 B., Kammerer2 U., Kuhn1 M.
1Physiology Institute I, Wrzburg University, Wrzburg, Germany
2Women's Hospital, University of Wrzburg, Wrzburg, Germany
Atrial natriuretic peptide (ANP) is critically involved in the maintenance of arterial blood pressure and intravascular volume. Its cGMP-forming guanylyl cyclase-A (GC-A) receptor is densely expressed in vascular endothelium, but the functional relevance is controversial since both hypo- and hyperpermeability effects were observedin vitro. Here we combined intravital microscopy studies of the mouse cremaster microcirculation with experiments on cultured endothelial cells to characterize the endothelial permeability effects of ANP and mediating (post)receptor signaling pathways.
In vivo, ANP (100 nM, local superfusion) mildly stimulated the extravasation of fluorescent albumin from post-capillary venules and caused arteriolar vasodilatation. The hyperpermeability effect was prevented in mice with conditional, endothelial deletion of GC-A (EC GC-A KO), while the vasodilatory action was preserved. Intriguingly, ANP had no direct effect on the extravasation of fluorescent dextran, but strongly reduced the histamine (2 mM) - provoked vascular leakage of the macromolecule. Notably, this anti-inflammatory effect of ANP was also prevented in EC GC-A KO mice. In vitro, in cultured human umbilical vein endothelial cells (HUVEC), ANP enhanced intracellular cGMP levels but this did not affect transendothelial electrical resistance (TEER) and intracellular calcium homeostasis. However, ANP attenuated the breakdown of TEER and the Ca2+i rises induced by histamine.
We conclude that ANP exerts dual effects on microcirculatory endothelial permeability. Beyond the direct physiological mild permeability-increasing (volume-regulating) effects onquiescentendothelial cells, ANP exerts the opposite, namely barrier-enhancing effects on aninflammation-activatedendothelium in the systemic circulation.Supported by SFB 688.
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Acta Physiologica 2012; Volume 204, Supplement 689 :P198