Mechanisms of Nitric Oxide Uptake by Cells

 The balance between vasoconstrictors and vasodilators modulates blood pressure.  Nitric oxide (NO), a vasodilator, is produced from endothelial cells and activates soluble guanylyl cyclase in smooth muscle cells to induce vasodilation.  Although extensive studies have been directed to the biosynthesis of NO in physiological and pathological conditions, the diffusion of NO in the tissues has received less attention and is poorly understood.  Recently, it has been shown that the NO bioavailability can be modulated by erythrocytes, but whether NO uptake by smooth muscle cells could also be altered is still unknown.  If it could, the alteration of NO uptake may contribute, at least in part, to the result of hypertension or septic shock.  In order to determine whether NO uptake by smooth muscle cells may be altered in a pathological condition, first we design a competition experiment to measure and calculate the NO uptake by smooth muscle cells.  Second, the factors of hypertension such as triglyceride, low-density lipoprotein, and oxidized low-density lipoprotein were added to smooth muscle cells and their effects on NO uptake were identified.  We found out that the intracellular superoxide in smooth muscle cells is the determinant for the NO uptake by cells. This aspect is a new approach to diagnosing the factors of hypertension and is important to the development of clinical intervention.