Key result
Atrial natriuretic peptide (ANP) and C-ANP 4-23 inhibited the synthesis of endothelin-1 proteins by at least 50% and secretion by up to 55% in cultured bovine aortic endothelial cells.
ANP inhibits ET-1 protein production and secretion in endothelial cells via the C receptor, highlighting a novel regulatory interaction in the vasculature.
Should not change clinical practice; leaves open ANP-ET-1 interactions in human vascular disease.
Atrial natriuretic peptide (ANP) and endothelin-1 (ET-1) are vasoactive peptides produced in cells of the cardiovascular system. We examined the effects of ANP on ET-1 transcription, production (translation), and secretion in cultured bovine aortic endothelial cells (BAEC). ANP and C-ANP 4-23 (a specific ligand for the C or non-guanylate cyclase receptor) equipotently inhibited the synthesis of prepro-ET-1 and ET-1 proteins in BAEC by at least 50%. Both of these forms of ANP and another C receptor specific ligand, nanopiperazine ANP (11-15)-NH2, inhibited ET-1 secretion by as much as 55%. LY 83583, an inhibitor of ANP-induced cGMP generation, failed to reverse the ANP-induced inhibition of ET-1 secretion. This further indicated that the guanylate cyclase-linked B receptor is not involved. The decreased ET-1 secretion caused by C-ANP 4-23 was reversed by 8-bromo-cAMP or amiloride, which prevents ANP-induced inhibition of cAMP. We also found that ANP and C-ANP 4-23 augmented ET-1 mRNA levels in BAEC by prolonging the mRNA half-life. ANP or cycloheximide comparably inhibited ET-1 translation while increasing ET-1 mRNA levels, suggesting that the two events are related. These results indicate that ANP inhibits ET-1 protein production and secretion while stabilizing the ET-1 mRNA. The effects of ANP are mediated through the C receptor and are probably the result of ANP inhibiting the generation of cAMP. These findings suggest a potentially important new function for this receptor to mediate, in part, the interactions of ANP and ET in the vasculature.
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Hu et al. (1992) studied Cultured bovine aortic endothelial cells (in vitro). Atrial natriuretic peptide (ANP) and C-ANP 4-23 was evaluated on ET-1 transcription, production, and secretion. Atrial natriuretic peptide (ANP) and C-ANP 4-23 inhibited the synthesis of endothelin-1 proteins by at least 50% and secretion by up to 55% in cultured bovine aortic endothelial cells.
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