Atrial natriuretic peptide attenuates thrombin‐induced inflammation (672.4)

Abstract

One microcirculatory homeostatic action of atrial natriuretic peptide (ANP) in the absence of inflammation is to increase barrier permeability to plasma proteins (Ps) when plasma volume is increased. However several investigations, particularly in cultured endothelial cells, suggest that high concentrations of ANP may also attenuate Ps. We tested the hypothesis that this action of ANP was characteristic of endothelium expressing a pro‐inflammatory phenotype. In individually perfused rat mesentery microvessels with no prior exposure to inflammation, pretreatment for 30 min with ANP (100 ng/ml) did not attenuate the increased permeability after exposure to bradykinin (10 nM). However in mouse skin where thrombin increased Ps 24 hours after an aseptic wound (AJP Heart, 296: 848, 2009), ANP added to the wound (50 ng/min/kg bw) significantly attenuated the thrombin induced transvascular albumin. At the same time, ANP attenuated thrombin induced neutrophil accumulation in the wound, and ANP alone increased Ps. Our results confirm that ANP acts to attenuate transvascular exchange in an intact microvasculature but only under inflammatory conditions. The mechanism of action appears to be independent of the normal ANP signaling pathways to increase Ps, and may involve reduced production of pro‐inflammatory agents from activated endothelium, neutrophils, or other inflammatory cells.Grant Funding Source: Supported by NIH HL28607