Regulation of Blood Flow by HbSNO

The oft-touted argument against a physiological role for HbSNO is that even if it does form in RBCs, the Hb-bound NO has to make quite a journey to get to smooth muscle cells it must first cross the RBC plasma membrane, then the RBC free zone (Liao et al., 1999), then cross the endothelial cell membranes twice and finally go through the smooth muscle membrane. Why would nature adopt such a convoluted route when the endothelial cells next to the smooth muscle cells are producing membrane-diffusable NO  

We and others have demonsttated that an endothelial, cell surface protein-disulfide isomerase-mediated mechanism, does exist for the rapid influx of RSNO bound-NO (Zai et al. 1999 Ramachandran et al., 2001). Whether the csPDI route plays a role in the transfer of NO-equivalents from RBCs remains to be answered. 

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