| 10619578 |
Orie NN, Zidek W, Tepel M: Reactive oxygen species in essential hypertension and non-insulin-dependent diabetes mellitus. Am J Hypertens. 1999 Dec;12(12 Pt 1-2):1169-74.
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 micromol/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/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-Phenylalanine-(fMLP)-induced ROS generation was significantly higher in NIDDM (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 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. |
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