Luminal endothelial lectins with affinity for N‐Acetylgucosamine determine flow‐induced cardiac and vascular paracrine responses

Abstract

Coronary endothelial luminal membrane (CELM) oligosaccharides (O) and lectins (L) are involved in flow detection. Flow may induce a reversible L‐O interaction causing flow‐induced endothelial (FIE) cardiac effects. Because N‐Acetylglucosamine (GlcNac) is a component of glycocalyx O, we isolated CELM GlcNac‐binding L (using GlcNac‐affinity probe) and show their role in cardiac and vascular FIE responses. The GlcNac‐affinity probe is a 460 kDa GlcNac polymer (GlcNac‐Pol). In the heart: 1) Intracoronary given GlcNac‐Pol upon binding to CELM, reduces the FIE inotropic and dromotropic effects. 2) GlcNac‐Pol used as an affinity probe isolated CELM GlcNac‐recognizing L; 35 individual L were identified, some of which likely participate in FIE and in GlcNac‐Pol‐induced effects. 3) In isolated blood vessels perfuse at controlled flow rates; FIE vasodilatation (FIEV) is blocked by: binding GlcNac‐Pol to CELM, Hyaluronidase, L‐NAME plus Indomethacin and Amiloride; a ENaC blocker. We also show ENac is present in CELM and is a L. These suggest FIEV is due to: a) FIE ENaC‐hyaluronidate (a GlcNac polymer) interaction, b) release of NO and prostaglandins and c) GlcNac‐Pol upon binding to ENaC inhibits release of paracrine mediators. Funded by CONACyT SEP‐42567, CONACyT‐SALUD 2004‐C01‐156.