Fig. 1

Role of nitic oxide (NO) in blood vessels and functional interplay between erythrocytes and platelets. NO is generated by the endothelial NO synthase (eNOS) upon stimulation by fluid shear stress or Ca²⁺ elevating agonists. The biological actions of NO, including platelet inhibition and smooth muscle relaxation, are mediated by the soluble guanylate cyclase (sGC), which generates cGMP and the subsequent activation of protein kinase G (PKG). Erythrocytes play a role in the regulation of platelet activation as ADP and ATP secreted from damaged erythrocytes directly stimulates platelet purinergic receptors (P2Y₁₂, P2Y₁, and P2X₁). Secreted hemoglobin (Hb) scavenges endothelial-derived NO and therefore decreases platelet inhibition. It has been proposed that erythrocytes also play a role in platelet inhibition by generation/release of NO or NO-carriers, such as SNO. While it is still debatable whether or not erythrocytes can generate NO/SNO, current experimental evidence by Gambaryan et al. concludes that erythrocytes do not release biologically active NO/SNO