title: Interactive effects of superoxide anion and nitric oxide on blood pressure and renal hemodynamics in transgenic rats with inducible malignant hypertension.
abstract: Superoxide anion contributes to the pathogenesis of various forms of hypertension, but its role in the development of malignant hypertension remains unclear. The present study was performed to determine the influence of superoxide anion on blood pressure and renal hemodynamics in transgenic rats with inducible malignant hypertension [strain name: TGR(Cyp1a1Ren2)]. Malignant hypertension was induced in male Cyp1a1-Ren2 rats (n = 6) through dietary administration of the aryl hydrocarbon, indole-3-carbinol (0.3%) for 7-9 days. Mean arterial pressure (MAP) and renal hemodynamics were measured in pentobarbital sodium-anesthetized Cyp1a1-Ren2 rats before and during intravenous infusion of the superoxide dismutase mimetic tempol (100 mumol/h). Basal MAP and renal vascular resistance (RVR) were elevated in rats induced with indole-3-carbinol compared with noninduced rats (n = 5) (184 +/- 4 vs. 127 +/- 3 mmHg, P < 0.01, and 29 +/- 2 vs. 21 +/- 1 mmHg.ml(-1).min.g, P < 0.01, respectively). Hypertensive rats had elevated excretion of urinary 8-isoprostane compared with normotensive rats (41 +/- 4 vs. 13 +/- 6 pg.min(-1).g(-1), P < 0.01). There were no differences in renal plasma flow and glomerular filtration rate between groups. Systemic administration of tempol decreased MAP (184 +/- 4 to 151 +/- 4 mmHg, P < 0.01) and RVR (29 +/- 2 to 25 +/- 2 mmHg.ml(-1).min.g, P < 0.05) in hypertensive but not in normotensive Cyp1a1-Ren2 rats. In addition, tempol administration decreased urinary excretion of 8-isoprostane (41 +/- 4 to 25 +/- 4 pg.min(-1).g(-1), P < 0.05). Renal plasma flow and glomerular filtration rate remained unaltered during tempol administration in both groups. The administration of the nitric oxide synthase inhibitor nitro-l-arginine attenuated the decrease in MAP and RVR in response to tempol. These findings indicate that superoxide anion contributes to the elevated RVR and increased arterial blood pressure, by a mechanism that is at least in part nitric oxide dependent, in Cyp1a1-Ren2 rats with malignant hypertension.
authors.affiliation: Dept. of Physiology, Tulane Univ. Health Sciences Center, 1430 Tulane Ave., SL39, New Orleans, LA 70112, USA. mpatters@tulane.edu
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Patterson
authors.forename: Cynthia R
authors.initials: CR
authors.lastname: Mouton
authors.forename: John J
authors.initials: JJ
authors.lastname: Mullins
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001794:Blood Pressure / Q000187:drug effects*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006974:Hypertension, Malignant / Q000378:metabolism*; D007677:Kidney Function Tests; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology*; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000235:genetics; D013113:Spin Labels; D013481:Superoxides / Q000494:pharmacology*; D019076:Transgenes / Q000235:genetics; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D016877:Oxidants; D013113:Spin Labels; D013481:Superoxides; D019335:Nitroarginine; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D019363:Cytochrome P-450 CYP1A1; D012083:Renin; C001803:tempol