Superoxide determines nitric oxide uptake rate by vascular smooth muscle cells

Nitric oxide (NO) is generated in endothelial cells, which diffuses to vascular smooth muscle cells (SMCs), activates soluble guanylyl cyclase, and leads to blood vessel dilation. However, this scenario does not explain how SMCs are capable of competing with erythrocytic hemoglobin for NO in vivo. Here, we have developed a competition experiment to determine the NO uptake rate by SMCs and demonstrated that the SMC-NO uptake rate is positively dependent on intracellular superoxide levels. In addition, the superoxide-elicited NO influx is able to enhance cGMP production in SMCs. Our findings imply that vascular SMCs, in vivo, may use superoxide to compete with erythrocytic hemoglobin for NO and obtain the NO bioactivity.