Reactive oxygen species in essential hypertension and non–insulin-dependent diabetes mellitus

To evaluate whether increased levels of reactive oxygen species (ROS) are involved in the pathogenesis of essential hypertension (EH) and non–insulin-dependent diabetes mellitus (NIDDM), both resting and stimulated levels of intracellular ROS were measured in lymphocytes from patients with EH (n = 10), NIDDM (n = 16) and age-matched healthy individuals (control subjects, n = 19). ROS was monitored with the dye, dihydrorhodamine-123 (DHR; 1 μmol/L) in the presence or absence of superoxide dismutase (superoxide scavenger), sodium azide (singlet oxygen/hydrogen peroxide scavenger), genistein (tyrosine kinase inhibitor), or bisindolylmaleimide (protein kinase C inhibitor). Simultaneous monitoring of cytosolic [Ca2+]i was done with fura-2. Resting ROS levels were significantly higher in NIDDM (4.71 ± 0.25 nmol/106 cells; mean ± SEM, P< .05) compared with EH (4.03 ± 0.22 nmol/106 cells) or controls (4.05 ± 0.15 nmol/106 cells). The formyl-Met-Leu-Phenylalanine-(fMLP)–induced ROS generation was significantly higher in NIDDM (21.92 ± 2.23 nmol/106 cells; P< .05) compared with EH (14.58 ± 1.90 nmol/106 cells) or control (16.06 ± 1.22 nmol/106 cells). The fMLP-induced ROS increase was significantly reduced in the presence of sodium azide in all groups (P< .01) but was largely unaffected in the presence of SOD. Genistein and bisindolylmaleimide significantly inhibited the fMLP-induced ROS in all groups. The fMLP-induced [Ca2+]i increase was significantly higher in NIDDM (71 ± 12 nmol/L, P< .01) compared with EH (42 ± 4 nmol/L) and control subjects (35 ± 3 nmol/L). Phytohemagglutinin was more effective in increasing [Ca2+]i than ROS. It is concluded that ROS may play a role in the metabolic syndrome of NIDDM but not in EH.