Therefore, although the enhanced constitutive NOS activity in vascular tissue of B1R−/− and B2R−/− mice, our findings indicate that the uncoupled activity of nNOS represents a remarkable source of superoxide and, may be the major cause of the endothelial dysfunction in B1R−/− and B2R−/− mice. The gene discussed is BDKRB2; the disease is endothelial dysfunction.