Functional coupling of oxygen binding and vasoactivity in S-nitrosohemoglobin

S-Nitrosohemoglobin (SNO-Hb) is a vasodilator whose activity is allosterica lly modulated by oxygen ("thermodynamic linkage"). Blood vessel contraction s are favored in the oxygenated structure, and vasorelaxant activity is 'li nked" to deoxygenation, as illustrated herein. We further show that transni trosation reactions between SNO-Hb and ambient thiols transduce the NO-rela ted bioactivity, whereas NO itself is inactive. One remaining problem is th at the amounts of SNO-Hb present in vivo are so large as to be incompatible with Life were all the S-nitrosothiols transformed into bioactive equivale nts during each arterial-venous cycle. Experiments were therefore undertake n to address how SNO-Hb, conserves its NO-related activity. Our studies sho w that 1) increased O-2 affinity of SNO-Hb (which otherwise retains alloste ric responsivity) restricts the hypoxia-induced allosteric transition that exchanges NO groups with ambient thiols for vasorelaxation; 2) some NO grou ps released from Cys(beta 93) upon transition to T structure are autocaptur ed by the hemes, even in the presence of glutathione; and 3) an O-2-depende nt equilibrium between SNO-Hb and iron nitrosylhemoglobin acts to conserve NO. Thus, by sequestering a significant fraction of NO liberated upon trans ition to T structure, Hb can conserve NO groups that would otherwise be rel eased in an untimely or deleterious manner.