The atrial natriuretic peptide regulates the production of inflammatory mediators in macrophages

The atrial natriuretic peptide (ANP), a member of the natriuretic peptide f amily, is a cardiovascular hormone which possesses well defined natriuretic , diuretic, and vasodilating properties. Most of the biological effects of ANP are mediated through its guanylyl cyclase coupled A receptor. Because A NP and its receptors have been shown to be expressed and differentially reg ulated in the immune system, it has been suggested that ANP has an immunomo dulatory potency. Much investigation of the effects of ANP on the activation of macrophages h as been carried out. ANP was shown to inhibit the lipopolysaccharide (LPS)- induced expression of inducible nitric oxide synthase (iNOS) in macrophages in an autocrine fashion. ANP in this context was shown to reduce significa ntly the activation of NF-kappaB and to destabilise iNOS mRNA. ANP, further more, can significantly reduce the LPS-induced secretion of tumour necrosis factor alpha (TNF alpha) in macrophages. The relevance of these findings o n a regulatory role for ANP on TNF alpha in humans was shown by the fact th at ANP significantly reduces the release of TNF alpha in whole human blood. It was furthermore shown to attenuate the release of interleukin 1 beta (I L1 beta). Interestingly, ANP did not affect the secretion of the antiinflam matory cytokines IL10 and IL1 receptor antagonist (ILlra). In summary, ANP was shown to reduce the secretion of inflammatory mediators in macrophages. Therefore, this cardiovascular hormone may possess antiinf lammatory potential.