BACKGROUND: Nitric oxide (NO) and related molecules are thought to inhibit human platelet aggregation by raising levels of cGMP. METHODS AND RESULTS: Both oxidative stress (reactive oxygen species) and hemoglobin (Hb) seem to oppose NO effects. A major fraction of NO in the blood is bound to thiols of Hb, forming S-nitrosohemoglobin (SNO-Hb), which releases the NO group on deoxygenation in the microcirculation. Here we show that (1) both cell-free and intraerythrocytic SNO-Hb (SNO-RBC) inhibit platelet aggregation, (2) the oxidation state of the hemes in Hb influences the response--SNO-metHb (which is functionally similar to SNO-deoxyHb) has greater platelet inhibitory effects than SNO-oxyHb, and (3) the mechanism of platelet inhibition by SNO-Hb is cGMP independent. CONCLUSIONS: We suggest that the RBC has evolved a means to counteract platelet activation in small vessels and the proaggregatory effects of oxidative stress by forming SNO-Hb.
BACKGROUND:Nitric oxide (NO) and related molecules are thought to inhibit humanplatelet aggregation by raising levels of cGMP. METHODS AND RESULTS: Both oxidative stress (reactive oxygen species) and hemoglobin (Hb) seem to oppose NO effects. A major fraction of NO in the blood is bound to thiols of Hb, forming S-nitrosohemoglobin (SNO-Hb), which releases the NO group on deoxygenation in the microcirculation. Here we show that (1) both cell-free and intraerythrocytic SNO-Hb (SNO-RBC) inhibit platelet aggregation, (2) the oxidation state of the hemes in Hb influences the response--SNO-metHb (which is functionally similar to SNO-deoxyHb) has greater platelet inhibitory effects than SNO-oxyHb, and (3) the mechanism of platelet inhibition by SNO-Hb is cGMP independent. CONCLUSIONS: We suggest that the RBC has evolved a means to counteract platelet activation in small vessels and the proaggregatory effects of oxidative stress by forming SNO-Hb.
Authors: Craig N Morrell; Kenji Matsushita; Kelly Chiles; Robert B Scharpf; Munekazu Yamakuchi; Rebecca J A Mason; Wolfgang Bergmeier; Joseph L Mankowski; William M Baldwin; Nauder Faraday; Charles J Lowenstein Journal: Proc Natl Acad Sci U S A Date: 2005-02-28 Impact factor: 11.205
Authors: Jun-Yan Liu; Ning Li; Jun Yang; Nan Li; Hong Qiu; Ding Ai; Nipavan Chiamvimonvat; Yi Zhu; Bruce D Hammock Journal: Proc Natl Acad Sci U S A Date: 2010-09-13 Impact factor: 11.205