Hypoxic potentiation of nitrite effects in human vessels and platelets

Mechanisms of Human Erythrocytic Bioactivation of Nitrite

“…Importantly, two groups have now shown that nitrite also inhibits platelets systemically in humans; however, this effect only occurs in vitro with exposure of nitrite to whole blood with no effects observed on isolated platelet rich plasma (35,38). This in vivo effect is potentiated under hypoxia, again consistent with hemoglobin deoxygenation (35). Thus, there is substantial evidence supporting a role of the red blood cell in nitrite bioactivation.…”

“…Experiments performed with aortic ring bioassays showed that nitritemediated vasodilation, which increases as the oxygen tension decreases, is increased when red blood cells are present (5). Although this action of red blood cells was challenged in one study (34), subsequent studies clearly demonstrate that NO scavenging by Hb is counterbalanced by nitrite-mediated NO production from deoxyHb (35,36).…”

“…More recently, significant support for a physiological role of the red blood cell in the bioactivation of nitrite and NO signaling comes from studies examining platelet activation by nitrite and red cells (35,37,38). NO is known to inhibit platelet activation via soluble guanylate cyclase activation and cGMP signaling (39 -42).…”

“…Whereas nitrite alone has no effect on platelet activation, when nitrite is added in combination with red blood cells, platelet activation is inhibited in association with intracellular platelet cGMP formation (37). The inhibition of platelet activation by nitrite and red blood cells is abrogated by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO) and promoted by deoxygenation of the red blood cell (35,37,38). Importantly, two groups have now shown that nitrite also inhibits platelets systemically in humans; however, this effect only occurs in vitro with exposure of nitrite to whole blood with no effects observed on isolated platelet rich plasma (35,38).…”

“…The inhibition of platelet activation by nitrite and red blood cells is abrogated by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO) and promoted by deoxygenation of the red blood cell (35,37,38). Importantly, two groups have now shown that nitrite also inhibits platelets systemically in humans; however, this effect only occurs in vitro with exposure of nitrite to whole blood with no effects observed on isolated platelet rich plasma (35,38). This in vivo effect is potentiated under hypoxia, again consistent with hemoglobin deoxygenation (35).…”