title: Reactive oxygen species in essential hypertension and non-insulin-dependent diabetes mellitus.
abstract: 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.
authors.affiliation: Universitätsklinik Marienhospital, University of Bochum, Germany.
authors.forename: N N
authors.initials: NN
authors.lastname: Orie
authors.forename: W
authors.initials: W
authors.lastname: Zidek
authors.forename: M
authors.initials: M
authors.lastname: Tepel
mesh_terms: D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000097:blood*; D007424:Intracellular Fluid / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018384:Oxidative Stress; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012235:Rhodamines / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; D012235:Rhodamines; C058319:dihydrorhodamine 123; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013482:Superoxide Dismutase; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D002118:Calcium; D016257:Fura-2