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

To evaluate whether increased levels of reactive oxygen species (ROS) are i nvolved 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 = 1 0), NIDDM (n = 16) and age-matched healthy individuals (control subjects, n = 19). ROS was monitored with the dye, dihydrorhodamine-123 (DHR; 1 mu mol /L) in the presence or absence of superoxide dismutase (superoxide scavenge r), sodium azide (singlet oxygen/hydrogen peroxide scavenger), genistein (t yrosine kinase inhibitor), or bisindolylmaleimide (protein kinase C inhibit or). Simultaneous monitoring of cytosolic [Ca2+](i) was done with fura-2. R esting ROS levels were significantly higher in NIDDM (4.71 +/- 0.25 nmol/10 (6) cells; mean +/- SEM, P < .05) compared with EH (4.03 +/- 0.22 nmol/10(6 ) cells) or controls (4.05 +/- 0.15 nmol/10(6) cells). The formyl-Met-Leu-P henylalanine-(fMLP)-induced ROS generation was significantly higher in NIDD M (21.92 +/- 2.23 nmol/10(6) cells; P < .05) compared with EH (14.58 +/- 1. 90 nmol/10(6) cells) or control (16.06 +/- 1.22 nmol/10(6) cells). The fMLP -induced ROS increase was significantly reduced in the presence of sodium a zide in all groups (P < .01) but was largely unaffected in the presence of SOD. Genistein and bisindolylmaleimide significantly inhibited the fMLP-ind uced ROS in all groups. The fMLP-induced [Ca2+](i) increase was significant ly higher in NIDDM (71 +/- 12 nmol/L, P < .01) compared with EH (42 +/- 4 n mol/L) and control subjects (35 +/- 3 nmol/L). Phytohemagglutinin was more effective in increasing [Ca2+], than ROS. It is concluded that ROS may play a role in the metabolic syndrome of NIDDM but not in EH. Am J Hypertens 19 99;12:1169-1174 (C) 1999 American Journal of Hypertension, Ltd.