We thank Dr Tsuda1 for his interest in our work and his insightful comments. We agree with Dr Tsuda1 that it is interesting and important to elucidate the role of nitric oxide (NO) bioavailability, including asymmetric dimethyl arginine (ADMA, an endogenous NO synthase inhibitor) levels in the development of vascular insulin resistance and hypertension. Insulin-induced vasorelaxation contributes to the maintenance of microvascular tone and vascular resistance. Therefore, vascular insulin resistance plays a role in elevated peripheral vascular resistance and subsequent hypertension. However, mechanisms responsible for vascular insulin resistance during the prehypertensive stage remain elusive. Recently, we found that hypoadiponectinemia induces low APPL1 (an adaptor protein that mediates adiponectin signaling) expression …