title: Systemic arterial pressure response to two weeks of Tempol therapy in SHR: involvement of NO, the RAS, and oxidative stress.
abstract: The roles of nitric oxide (NO) and plasma renin activity (PRA) in the depressor response to chronic administration of Tempol in spontaneously hypertensive rats (SHR) are not clear. The present study was done to determine the effect of 2 wk of Tempol treatment on blood pressure [mean arterial pressure (MAP)], oxidative stress, and PRA in the presence or absence of chronic NO synthase inhibition. SHR were divided into four groups: control, Tempol (1 mmol/l) alone, nitro-L-arginine methyl ester (L-NAME, 4.5 mg x g(-1).day(-1)) alone, and Tempol + L-NAME or 2 wk. With Tempol, MAP decreased by 22%: 191 +/- 3 and 162 +/- 21 mmHg for control and Tempol, respectively (P < 0.05). L-NAME increased MAP by 16% (222 +/- 2 mmHg, P < 0.01), and L-NAME + Tempol abolished the depressor response to Tempol (215 +/- 3 mmHg, P < 0.01). PRA was not affected by Tempol but was increased slightly with L-NAME alone and 4.4-fold with L-NAME + Tempol. Urinary nitrate/nitrite increased with Tempol and decreased with L-NAME and L-NAME + Tempol. Tempol significantly reduced oxidative stress in the presence and absence of L-NAME. In conclusion, in SHR, Tempol administration for 2 wk reduces oxidative stress in the presence or absence of NO, but in the absence of NO, Tempol is unable to reduce MAP. Therefore, NO, but not changes in PRA, plays a major role in the blood pressure-lowering effects of Tempol. These data suggest that, in hypertensive individuals with endothelial damage and chronic NO deficiency, antioxidants may be able to reduce oxidative stress but not blood pressure.
authors.affiliation: Department. of Physiology and Biophysics, Univ. of Mississippi Medical Center, 2500 N. State St., Jackson, MS 39216-4505, USA.
authors.forename: Licy
authors.initials: L
authors.lastname: Yanes
authors.forename: Damian
authors.initials: D
authors.lastname: Romero
authors.forename: Radu
authors.initials: R
authors.lastname: Iliescu
authors.forename: Valeria E
authors.initials: VE
authors.lastname: Cucchiarelli
authors.forename: Lourdes A
authors.initials: LA
authors.lastname: Fortepiani
authors.forename: Francisco
authors.initials: F
authors.lastname: Santacruz
authors.forename: William
authors.initials: W
authors.lastname: Bell
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhang
authors.forename: Jane F
authors.initials: JF
authors.lastname: Reckelhoff
mesh_terms: D000166:Acridines / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000652:urine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008163:Luminescent Measurements; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000652:urine; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism
chemical_list: D000166:Acridines; D000959:Antihypertensive Agents; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D013113:Spin Labels; D013481:Superoxides; C033472:10,10'-dimethyl-9,9'-biacridinium; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D012083:Renin; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester