Oxidative stress contributes to chronic leg vasoconstriction in estrogen-deficient postmenopausal women

2007 ◽  
Vol 102 (3) ◽  
pp. 890-895 ◽  
Author(s):  
Kerrie L. Moreau ◽  
Ashley R. DePaulis ◽  
Kathleen M. Gavin ◽  
Douglas R. Seals
Keyword(s):  
Oxidative Stress ◽  
Blood Flow ◽  
Ascorbic Acid ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Postmenopausal Women ◽  
Oxidized Ldl ◽  
Duplex Ultrasound ◽  
Vascular Conductance ◽  
Leg Blood Flow

Basal whole leg blood flow and vascular conductance are reduced in estrogen-deficient postmenopausal compared with premenopausal women. The underlying mechanisms are unknown, but oxidative stress could be involved. We studied 9 premenopausal [23 ± 1 yr (mean ± SE)] and 20 estrogen-deficient postmenopausal (55 ± 1 yr) healthy women. During baseline control, oxidized low-density lipoprotein (LDL), a marker of oxidative stress, was 50% greater in the postmenopausal women ( P < 0.001). Basal whole leg blood flow (duplex ultrasound of femoral artery) was 34% lower in the postmenopausal women because of a 38% lower leg vascular conductance ( P < 0.0001); mean arterial pressure was not different. Intravenous administration of a supraphysiological dose of the antioxidant ascorbic acid increased leg blood flow by 15% in the postmenopausal women as a result of an increase in leg vascular conductance (both P < 0.001), but it did not affect leg blood flow in premenopausal controls or mean arterial pressure in either group. In the pooled subjects, the changes in leg blood flow and leg vascular conductance with ascorbic acid were related to baseline plasma oxidized LDL ( r = 0.46 and 0.53, P < 0.01) and waist-to-hip ratio and total body fat ( r = 0.41–0.44, all P < 0.05). Our results are consistent with the hypothesis that oxidative stress contributes to chronic leg vasoconstriction and reduced basal whole leg blood flow in estrogen-deficient postmenopausal women. This oxidative stress-related suppression of leg vascular conductance and blood flow may be linked in part to increased total and abdominal adiposity.

High-dose ascorbic acid infusion abolishes chronic vasoconstriction and restores resting leg blood flow in healthy older men

2007 ◽  
Vol 103 (5) ◽  
pp. 1715-1721 ◽  
Author(s):  
Kristen L. Jablonski ◽  
Douglas R. Seals ◽  
Iratxe Eskurza ◽  
Kevin D. Monahan ◽  
Anthony J. Donato
Keyword(s):  
Blood Flow ◽  
Ascorbic Acid ◽  
Femoral Artery ◽  
Oxidized Ldl ◽  
Older Men ◽  
Artery Blood Flow ◽  
Vascular Conductance ◽  
Acid Infusion ◽  
Leg Blood Flow ◽  
Femoral Artery Blood Flow

Resting whole leg blood flow and vascular conductance decrease linearly with advancing age in healthy adult men. The potential role of age-related increases in oxidative stress in these changes is unknown. Resting leg blood flow during saline and ascorbic acid infusion was studied in 10 young (25 ± 1 yr) and 11 older (63 ± 2 yr) healthy normotensive men. Plasma oxidized LDL, a marker of oxidative stress, was greater in the older men ( P < 0.05). Absolute resting femoral artery blood flow at baseline (iv saline control infusion) was 25% lower in the older men (238 ± 25 vs. 316 ± 38 ml/min; P < 0.05), and it was inversely related to plasma oxidized LDL ( r = −0.56, P < 0.01) in all subjects. Infusion of supraphysiological concentrations of ascorbic acid increased femoral artery blood flow by 37% in the older men (to 327 ± 52 ml/min; P < 0.05), but not in the young men (352 ± 41 ml/min; P = 0.28), thus abolishing group differences ( P = 0.72). Mean arterial blood pressure was greater in the older men at baseline (86 ± 4 vs. 78 ± 2 mmHg; P < 0.05), but it was unaffected by ascorbic acid infusion ( P ≥ 0.70). As a result, the lower baseline femoral artery blood flow in the older men was mediated solely by a 32% lower femoral artery vascular conductance ( P < 0.05). Baseline femoral vascular conductance also was inversely related to plasma oxidized LDL ( r = −0.65, P < 0.01). Ascorbic acid increased femoral vascular conductance by 36% in the older men ( P < 0.05) but not in the young men ( P = 0.31). In conclusion, ascorbic acid infused at concentrations known to scavenge reactive oxygen species restores resting femoral artery blood flow in healthy older adult men by increasing vascular conductance. These results support the hypothesis that oxidative stress plays a major role in the reduced resting whole leg blood flow and increased leg vasoconstriction observed with aging in men.

Leg vasoconstriction during dynamic exercise with reduced cardiac output

1992 ◽  
Vol 73 (5) ◽  
pp. 1838-1846 ◽  
Author(s):  
J. A. Pawelczyk ◽  
B. Hanel ◽  
R. A. Pawelczyk ◽  
J. Warberg ◽  
N. H. Secher
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Cardiac Output ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Dynamic Exercise ◽  
Adrenergic Blockade ◽  
Vascular Conductance ◽  
Leg Blood Flow ◽  
Norepinephrine Spillover

We evaluated whether a reduction in cardiac output during dynamic exercise results in vasoconstriction of active skeletal muscle vasculature. Nine subjects performed four 8-min bouts of cycling exercise at 71 +/- 12 to 145 +/- 13 W (40-84% maximal oxygen uptake). Exercise was repeated after cardioselective (beta 1) adrenergic blockade (0.2 mg/kg metoprolol iv). Leg blood flow and cardiac output were determined with bolus injections of indocyanine green. Femoral arterial and venous pressures were monitored for measurement of heart rate, mean arterial pressure, and calculation of systemic and leg vascular conductance. Leg norepinephrine spillover was used as an index of regional sympathetic activity. During control, the highest heart rate and cardiac output were 171 +/- 3 beats/min and 18.9 +/- 0.9 l/min, respectively. beta 1-Blockade reduced these values to 147 +/- 6 beats/min and 15.3 +/- 0.9 l/min, respectively (P < 0.001). Mean arterial pressure was lower than control during light exercise with beta 1-blockade but did not differ from control with greater exercise intensities. At the highest work rate in the control condition, leg blood flow and vascular conductance were 5.4 +/- 0.3 l/min and 5.2 +/- 0.3 cl.min-1.mmHg-1, respectively, and were reduced during beta 1-blockade to 4.8 +/- 0.4 l/min (P < 0.01) and 4.6 +/- 0.4 cl.min-1.mmHg-1 (P < 0.05). During the same exercise condition leg norepinephrine spillover increased from a control value of 2.64 +/- 1.16 to 5.62 +/- 2.13 nM/min with beta 1-blockade (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Is postexercise hypotension related to excess postexercise oxygen consumption through changes in leg blood flow?

2005 ◽  
Vol 98 (4) ◽  
pp. 1463-1468 ◽  
Author(s):  
Jay T. Williams ◽  
Mollie P. Pricher ◽  
John R. Halliwill
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Muscle Blood Flow ◽  
Causal Link ◽  
Skeletal Muscle Blood Flow ◽  
Leg Blood Flow ◽  
Postexercise Hypotension

After a single bout of aerobic exercise, oxygen consumption remains elevated above preexercise levels [excess postexercise oxygen consumption (EPOC)]. Similarly, skeletal muscle blood flow remains elevated for an extended period of time. This results in a postexercise hypotension. The purpose of this study was to explore the possibility of a causal link between EPOC, postexercise hypotension, and postexercise elevations in skeletal muscle blood flow by comparing the magnitude and duration of these postexercise phenomena. Sixteen healthy, normotensive, moderately active subjects (7 men and 9 woman, age 20–31 yr) were studied before and through 135 min after a 60-min bout of upright cycling at 60% of peak oxygen consumption. Resting and recovery V̇o2 were measured with a custom-built dilution hood and mass spectrometer-based metabolic system. Mean arterial pressure was measured via an automated blood pressure cuff, and femoral blood flow was measured using ultrasound. During the first hour postexercise, V̇o2 was increased by 11 ± 2%, leg blood flow was increased by 51 ± 18%, leg vascular conductance was increased by 56 ± 19%, and mean arterial pressure was decreased by 2.2 ± 1.0 mmHg (all P < 0.05 vs. preexercise). At the end of the protocol, V̇o2 remained elevated by 4 ± 2% ( P < 0.05), whereas leg blood flow, leg vascular conductance, and mean arterial pressure returned to preexercise levels (all P > 0.7 vs. preexercise). Taken together, these data demonstrate that EPOC and the elevations in skeletal muscle blood flow underlying postexercise hypotension do not share a common time course. This suggests that there is no causal link between these two postexercise phenomena.

scholarly journals Aerobic training and cutaneous vasodilation in young and older men

1999 ◽  
Vol 86 (5) ◽  
pp. 1676-1686 ◽  
Author(s):  
Carla M. Thomas ◽  
Jane M. Pierzga ◽  
W. Larry Kenney
Keyword(s):  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Aerobic Training ◽  
Older Men ◽  
Vascular Conductance ◽  
Doppler Flowmetry ◽  
Forearm Vascular Conductance ◽  
Response To Exercise ◽  
Cutaneous Vascular Conductance

To determine the effect and underlying mechanisms of exercise training and the influence of age on the skin blood flow (SkBF) response to exercise in a hot environment, 22 young (Y; 18–30 yr) and 21 older (O; 61–78 yr) men were assigned to 16 wk of aerobic (A; YA, n = 8; OA, n = 11), resistance (R; YR, n = 7; OR, n = 3), or no training (C; YC, n = 7; OC, n = 7). Before and after treatment, subjects exercised at 60% of maximum oxygen consumption (V˙o 2 max) on a cycle ergometer for 60 min at 36°C. Cutaneous vascular conductance, defined as SkBF divided by mean arterial pressure, was monitored at control (vasoconstriction intact) and bretylium-treated (vasoconstriction blocked) sites on the forearm using laser-Doppler flowmetry. Forearm vascular conductance was calculated as forearm blood flow (venous occlusion plethysmography) divided by mean arterial pressure. Esophageal and skin temperatures were recorded. Only aerobic training (functionally defined a priori as a 5% or greater increase inV˙o 2 max) produced a decrease in the mean body temperature threshold for increasing forearm vascular conductance (36.89 ± 0.08 to 36.63 ± 0.08°C, P < 0.003) and cutaneous vascular conductance (36.91 ± 0.08 to 36.65 ± 0.08°C, P < 0.004). Similar thresholds between control and bretylium-treated sites indicated that the decrease was mediated through the active vasodilator system. This shift was more pronounced in the older men who presented greater training-induced increases in V˙o 2 maxthan did the young men (22 and 9%, respectively). In summary, older men improved their SkBF response to exercise-heat stress through the effect of aerobic training on the cutaneous vasodilator system.

scholarly journals Central and peripheral contributors to skeletal muscle hyperemia: response to passive limb movement

2010 ◽  
Vol 108 (1) ◽  
pp. 76-84 ◽  
Author(s):  
John McDaniel ◽  
Anette S. Fjeldstad ◽  
Steve Ives ◽  
Melissa Hayman ◽  
Phil Kithas ◽  
...  
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Cardiac Output ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Stroke Volume ◽  
Limb Movement ◽  
Leg Blood Flow ◽  
Passive Exercise

The central and peripheral contributions to exercise-induced hyperemia are not well understood. Thus, utilizing a reductionist approach, we determined the sequential peripheral and central responses to passive exercise in nine healthy men (33 ± 9 yr). Cardiac output, heart rate, stroke volume, mean arterial pressure, and femoral blood flow of the passively moved leg and stationary (control) leg were evaluated second by second during 3 min of passive knee extension with and without a thigh cuff that occluded leg blood flow. Without the thigh cuff, significant transient increases in cardiac output (1.0 ± 0.6 l/min, Δ15%), heart rate (7 ± 4 beats/min, Δ12%), stroke volume (7 ± 5 ml, Δ7%), passive leg blood flow (411 ± 146 ml/min, Δ151%), and control leg blood flow (125 ± 68 ml/min, Δ43%) and a transient decrease in mean arterial pressure (3 ± 3 mmHg, 4%) occurred shortly after the onset of limb movement. Although the rise and fall rates of these variables differed, they all returned to baseline values within 45 s; therefore, continued limb movement beyond 45 s does not maintain an increase in cardiac output or net blood flow. Similar changes in the central variables occurred when blood flow to the passively moving leg was occluded. These data confirm the role of peripheral factors and reveal an essential supportive role of cardiac output in the hyperemia at the onset of passive limb movement. This cardiac output response provides an important potential link between the physiology of active and passive exercise.

scholarly journals Oral antioxidants improve leg blood flow during exercise in patients with chronic obstructive pulmonary disease

2015 ◽  
Vol 309 (5) ◽  
pp. H977-H985 ◽  
Author(s):  
Matthew J. Rossman ◽  
Joel D. Trinity ◽  
Ryan S. Garten ◽  
Stephen J. Ives ◽  
Jamie D. Conklin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Obstructive Pulmonary Disease ◽  
Blood Flow ◽  
Pulmonary Disease ◽  
Healthy Subjects ◽  
Chronic Obstructive ◽  
Vascular Conductance ◽  
Obstructive Pulmonary Disease ◽  
Leg Blood Flow ◽  
The Impact

The consequence of elevated oxidative stress on exercising skeletal muscle blood flow as well as the transport and utilization of O2 in patients with chronic obstructive pulmonary disease (COPD) is not well understood. The present study examined the impact of an oral antioxidant cocktail (AOC) on leg blood flow (LBF) and O2 consumption during dynamic exercise in 16 patients with COPD and 16 healthy subjects. Subjects performed submaximal (3, 6, and 9 W) single-leg knee extensor exercise while LBF (Doppler ultrasound), mean arterial blood pressure, leg vascular conductance, arterial O2 saturation, leg arterial-venous O2 difference, and leg O2 consumption (direct Fick) were evaluated under control conditions and after AOC administration. AOC administration increased LBF (3 W: 1,604 ± 100 vs. 1,798 ± 128 ml/min, 6 W: 1,832 ± 109 vs. 1,992 ± 120 ml/min, and 9W: 2,035 ± 114 vs. 2,187 ± 136 ml/min, P < 0.05, control vs. AOC, respectively), leg vascular conductance, and leg O2 consumption (3 W: 173 ± 12 vs. 210 ± 15 ml O2/min, 6 W: 217 ± 14 vs. 237 ± 15 ml O2/min, and 9 W: 244 ± 16 vs 260 ± 18 ml O2/min, P < 0.05, control vs. AOC, respectively) during exercise in COPD, whereas no effect was observed in healthy subjects. In addition, the AOC afforded a small, but significant, improvement in arterial O2 saturation only in patients with COPD. Thus, these data demonstrate a novel beneficial role of AOC administration on exercising LBF, O2 consumption, and arterial O2 saturation in patients with COPD, implicating oxidative stress as a potential therapeutic target for impaired exercise capacity in this population.

scholarly journals Ten days of repeated local forearm heating does not affect cutaneous vascular function

2017 ◽  
Vol 123 (2) ◽  
pp. 310-316 ◽  
Author(s):  
Michael A. Francisco ◽  
Vienna E. Brunt ◽  
Krista Nicole Jensen ◽  
Santiago Lorenzo ◽  
Christopher T. Minson
Keyword(s):  
Blood Flow ◽  
Young Adults ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Vascular Function ◽  
Forearm Blood Flow ◽  
Local Heating ◽  
Laser Doppler ◽  
Vascular Conductance ◽  
Doppler Flowmetry

The aim of the present study was to determine whether 10 days of repeated local heating could induce peripheral adaptations in the cutaneous vasculature and to investigate potential mechanisms of adaptation. We also assessed maximal forearm blood flow to determine whether repeated local heating affects maximal dilator capacity. Before and after 10 days of heat training consisting of 1-h exposures of the forearm to 42°C water or 32°C water (control) in the contralateral arm (randomized and counterbalanced), we assessed hyperemia to rapid local heating of the skin ( n = 14 recreationally active young subjects). In addition, sequential doses of acetylcholine (ACh, 1 and 10 mM) were infused in a subset of subjects ( n = 7) via microdialysis to study potential nonthermal microvascular adaptations following 10 days of repeated forearm heat training. Skin blood flow was assessed using laser-Doppler flowmetry, and cutaneous vascular conductance (CVC) was calculated as laser-Doppler red blood cell flux divided by mean arterial pressure. Maximal cutaneous vasodilation was achieved by heating the arm in a water-spray device for 45 min and assessed using venous occlusion plethysmography. Forearm vascular conductance (FVC) was calculated as forearm blood flow divided by mean arterial pressure. Repeated forearm heating did not increase plateau percent maximal CVC (CVCmax) responses to local heating (89 ± 3 vs. 89 ± 2% CVCmax, P = 0.19), 1 mM ACh (43 ± 9 vs. 53 ± 7% CVCmax, P = 0.76), or 10 mM ACh (61 ± 9 vs. 85 ± 7% CVCmax, P = 0.37, by 2-way repeated-measures ANOVA). There was a main effect of time at 10 mM ACh ( P = 0.03). Maximal FVC remained unchanged (0.12 ± 0.02 vs. 0.14 ± 0.02 FVC, P = 0.30). No differences were observed in the control arm. Ten days of repeated forearm heating in recreationally active young adults did not improve the microvascular responsiveness to ACh or local heating. NEW & NOTEWORTHY We show for the first time that 10 days of repeated forearm heating is not sufficient to improve cutaneous vascular responsiveness in recreationally active young adults. In addition, this is the first study to investigate cutaneous cholinergic sensitivity and forearm blood flow following repeated local heat exposure. Our data add to the limited studies regarding repeated local heating of the cutaneous vasculature.

scholarly journals A differing role of oxidative stress in the regulation of central and peripheral hemodynamics during exercise in heart failure

2012 ◽  
Vol 303 (10) ◽  
pp. H1237-H1244 ◽  
Author(s):  
Melissa A. H. Witman ◽  
John McDaniel ◽  
Anette S. Fjeldstad ◽  
Stephen J. Ives ◽  
Jia Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Cardiac Index ◽  
Arterial Pressure ◽  
Brachial Artery ◽  
Artery Blood Flow ◽  
Peripheral Hemodynamics

This study sought to characterize the role of free radicals in regulating central and peripheral hemodynamics at rest and during exercise in patients with heart failure (HF). We examined cardiovascular responses to dynamic handgrip exercise (4, 8, and 12 kg at 1 Hz) following consumption of either a placebo or acute oral antioxidant cocktail (AOC) consisting of vitamin C, E, and α-lipoic acid in a balanced, crossover design. Central and peripheral hemodynamics, mean arterial pressure, cardiac index, systemic vascular resistance (SVR), brachial artery blood flow, and peripheral (arm) vascular resistance (PVR) were determined in 10 HF patients and 10 age-matched controls. Blood assays evaluated markers of oxidative stress and efficacy of the AOC. When compared with controls, patients with HF exhibited greater oxidative stress, measured by malondialdehyde (+36%), and evidence of endogenous antioxidant compensation, measured by greater superoxide dismutase activity (+83%). The AOC increased plasma ascorbate (+50%) in both the HF patients and controls, but significant systemic hemodynamic effects were only evident in the patients with HF, both at rest and throughout exercise. Specifically, the AOC reduced mean arterial pressure (−5%) and SVR (−12%) and increased cardiac index (+7%) at each workload. In contrast, peripherally, brachial artery blood flow and PVR (arm) were unchanged by the AOC. In conclusion, these data imply that SVR in patients with HF is, at least in part, mediated by oxidative stress. However, this finding does not appear to be the direct result of muscle-specific changes in PVR.

Abstract 032: Uninterrupted Sitting Induces Unfavorable Changes In Resting Hemodynamics And Inflammatory And Vascular Biomarkers In Physically Inactive And Active Adults

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Megan C Nelson ◽  
Madeline P Casanova ◽  
Jennavere R Ball ◽  
Rachel D Midence ◽  
Timothy R Johnson ◽  
...  
Keyword(s):  
Physical Activity ◽  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Shear Rate ◽  
Arterial Pressure ◽  
Vascular Function ◽  
Blood Velocity ◽  
Inflammatory Biomarkers ◽  
Active Adults ◽  
Over Time

Introduction: A single bout of uninterrupted sitting impairs vascular function in the legs, which may be due to reductions in blood flow and shear stress. Participating in regular moderate-to-vigorous physical activity (MVPA) has been identified as an effective approach for improving vascular function, and recent evidence suggests meeting the physical activity (PA) guidelines may attenuate some of the negative health outcomes associated with excessive sedentary behavior; however, it is not well understood how meeting the PA guidelines may influence the acute response to sitting. Our aim was to investigate the effects of 3 h of uninterrupted sitting on hemodynamics and vascular and inflammatory biomarkers in physically inactive and active adults. Hypothesis: We hypothesized active adults would experience less detrimental physiological changes after sitting compared to inactive adults. Methods: Eleven inactive (mean±SD, age: 47.1±8.9 y, body fat: 33.1±8.5%; 78.5% women) and 16 active adults (age: 46.1±8.9 y, body fat: 25.2±7.2%; 31.1% women) completed 3 h of uninterrupted sitting. Adults self-reported their PA with the International PA Questionnaire. Adults engaging in ≥150 min·wk -1 were classified as active and <150 min·wk -1 , inactive. Hemodynamic variables, and superficial femoral artery (SFA) diameter and blood velocity were measured each hour over 3 h of sitting. Mean arterial pressure, blood flow and shear rate were calculated. Serum vascular and inflammatory biomarkers were measured pre and post sitting. Linear mixed-effects modeling was used to assess changes in dependent variables over time and between inactive and active adults, controlling for sex. Results: Inactive and active adults self-reported 7.3±7.1 and 93.3±64.8 min·d -1 of MVPA, respectively. Endothelin-1 (baseline: 8.3±13.4 pg/mL, post: 81.1±103.0 pg/mL; p<0.001) and interleukin-6 (baseline: 0.08±0.06 pg/mL, post: 0.11±0.11 pg/mL; p=0.03) increased post sitting compared to baseline in all adults, regardless of PA status. Systolic blood pressure, mean arterial pressure, calf circumference, and SFA diameter, blood velocity, and mean blood flow decreased over time in both groups (p<0.05 for all). There was an interaction effect for mean shear rate (p=0.008); inactive adults experienced a decline over 3 h of sitting (baseline: 76.1±48.2 s -1 ; 1 h: 55.0±27.4 s -1 ; 2 h: 45.3±24.2 s -1 ; 3 h: 40.8±25.5 s -1 ) while active participants demonstrated no change (baseline: 36.6±21.4 s -1 ; 1 h: 28.1±21.4 s -1 ; 2 h: 26.1±20.9 s -1 ; 3 h: 23.8±19.5 s -1 ). Inactive adults also had a higher oscillatory shear index compared to active adults (p<0.001). Conclusion: Uninterrupted sitting induced unfavorable changes regardless of PA status; however, active adults demonstrated a more favorable shear profile. Meeting PA guidelines may attenuate some unfavorable changes within the vasculature associated with prolonged sitting.

Abstract 316: Effects of Inhibiting of Inducible Nitric Oxide Synthase in the Pathophysiology of Experimental Preeclampsia

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Lorena M Amaral ◽  
Ana Carolina T Palei ◽  
Lucas C Pinheiro ◽  
Jonas T Sertorio ◽  
Danielle A Guimaraes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Inducible Nitric Oxide Synthase ◽  
Inos Expression ◽  
Oxygen Species ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The pathophysiology of preeclampsia (PE) is not entirely known. However, increased oxidative stress possibly leading to impaired nitric oxide activity has been implicated in the critical condition. Increased oxidative stress with increased levels of highly reactive species including superoxide may generate peroxynitrite. We examined the role of inducible nitric oxide synthase (iNOS) and oxidative stress in the reduced uterine perfusion pressure (RUPP) preeclampsia experimental model. METHODS: RUPP was induced in wistar rats. Pregnant rats in the RUPP group had their aortic artery clipped at day 14 of gestation. After a midline incision, a silver clip (0.203 mm) was placed around the aorta above the iliac bifurcation; silver clips (0.100 mm) were also placed on branches of both the right and left ovarian arteries that supply the uterus. Sham-operated (pregnant control rats) and RUPP rats were treated with oral vehicle or 1 mg/kg/day 1400W (iNOS inhibitor) for 5 days. Mean arterial pressure (MAP) and plasma levels of thiobarbituric acid-reactive species (TBARS) and total radical-trapping antioxidant potential (TRAP) were measured determined. Aortic iNOS expression (Western blotting) and reactive oxygen species (ROS; assessed by fluorescence microscopy with dihydroethidium-DHE) were measured. We found increased mean arterial pressure in RUPP compared with pregnant control rats (MAP= 128±1 vs. 100±1.8 mmHg, respectively; P<0.05) and 1400W exerted antihypertensive effects (MAP= 114±2 vs.128±1 mmHg in RUPP treated and untreated rats, respectively; P<0.05). Higher reactive oxygen species (ROS) concentrations were found in RUPP compared with pregnant control rats (7.1±0.5 vs. 5.1±0.5 arbitrary units (A.U.), respectively; P<0.05) and 1400W decreased ROS production to 5.8±0.02 A.U. in RUPP treated rats, P<0.05. In addition, 1400W attenuated iNOS expression in RUPP rats (0.29±0.02 vs. 0.55±0.8 A.U. in RUPP treated and untreated rats, respectively; P<0.01) and had no effects on plasma TBARS and TRAP levels. Our results suggest that 1400w exerts antihypertensive effects in the RUPP model and suppresses ROS formation. Supported by FAPESP,Cnpq.

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