scholarly journals N omega-amino-L-arginine, an inhibitor of nitric oxide synthase, raises vascular resistance but increases mortality rates in awake canines challenged with endotoxin.

1992 ◽  
Vol 176 (4) ◽  
pp. 1175-1182 ◽  
Author(s):  
J P Cobb ◽  
C Natanson ◽  
W D Hoffman ◽  
R F Lodato ◽  
S Banks ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Septic Shock ◽  
Mean Arterial Pressure ◽  
Nitric Oxide Synthase ◽  
Animal Models ◽  
Arterial Pressure ◽  
Vascular Resistance ◽  
Mortality Rates ◽  
High Dose ◽  
Oxide Synthase

Inhibitors of nitric oxide synthase (NOS) have been reported to increase mean arterial pressure in animal models of sepsis and recently have been given to patients in septic shock. However, controlled studies to determine the effects of these agents on cardiovascular function and survival in awake animal models of sepsis have not been reported. To examine the therapeutic potential of NOS inhibition in septic shock, we challenged canines with endotoxin (2 or 4 mg/kg i.v.) and treated them with either normal saline or N omega-amino-L-arginine (10 or 1 mg/kg/h), the most specific inhibitor available for the isoform of NOS implicated in septic shock. Endotoxemic animals treated with N omega-amino-L-arginine (n = 11) had higher systemic and pulmonary vascular resistance indices (SVRI and PVRI, p less than or equal to 0.033) and decreased heart rates (p = 0.009), cardiac indices (CI, p = 0.01), oxygen delivery indices (p = 0.027), and oxygen consumption indices (p = 0.046) compared with controls (n = 6). Moreover, N omega-amino-L-arginine increased mortality rates after endotoxin challenge (10 of 11 vs. 1 of 6 controls, p = 0.005). Administration of L-arginine did not improve survival or alter the cardiopulmonary effects of N omega-amino-L-arginine, which suggests that inhibition of NOS may not have been competitive. In normal animals, N omega-amino-L-arginine alone (n = 3) increased SVRI (p = 0.0008) and mean arterial pressure (p = 0.016), and decreased CI (p = 0.01) compared with saline-treated controls (n = 3), but, at the high dose, also produced neuromuscular rigidity and seizure-like activity that was not apparent in the endotoxemic model. Thus, the mortality rate from endotoxemia increased either because of NOS inhibition per se or because of properties unique to N omega-amino-L-arginine, or both.

Influence of nitric oxide on the hemodynamic response to hemorrhage in conscious rabbits

1995 ◽  
Vol 268 (1) ◽  
pp. R171-R182 ◽  
Author(s):  
M. A. Koch ◽  
E. M. Hasser ◽  
J. C. Schadt
Keyword(s):  
Nitric Oxide ◽  
Mean Arterial Pressure ◽  
Nitric Oxide Synthase ◽  
Arterial Pressure ◽  
Hemodynamic Response ◽  
Nitric Oxide Synthase Inhibitor ◽  
Acute Hemorrhage ◽  
Conscious Rabbits ◽  
Synthase Inhibitor ◽  
Oxide Synthase

We investigated the role of nitric oxide, an endothelium-derived relaxing factor, in the hemodynamic response to acute hemorrhage in conscious rabbits. Chronically instrumented rabbits were treated with the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) or vehicle and hemorrhaged until mean arterial pressure fell below 40 mmHg. Control animals were treated with L-NAME or vehicle but not subjected to hemorrhage. L-NAME increased mean arterial pressure and decreased heart rate in control animals. Hindquarters and mesenteric blood flow velocity and conductance were reduced by L-NAME. Nitric oxide synthase inhibition also produced significant changes in the hemodynamic response to hypotensive hemorrhage. Mean arterial pressure was higher and regional vascular conductances were lower throughout hemorrhage and during recovery. L-NAME treatment significantly (but in some cases, subtly) altered the characteristic pattern of changes in vascular conductance associated with acute hypotensive hemorrhage and recovery. Similar experiments with other arginine analogues or phenylephrine infusion showed that L-NAME's effects during hemorrhage were due to nitric oxide synthase inhibition. We conclude that nitric oxide plays a role in the hemodynamic response to acute hemorrhage in the rabbit and is essential for the full expression of the vasodilation associated with hypotensive hemorrhage.

Nitric oxide synthase inhibition partially prevents decreased LV contractility during endotoxemia

1996 ◽  
Vol 270 (6) ◽  
pp. H1979-H1984 ◽  
Author(s):  
M. J. Herbertson ◽  
H. A. Werner ◽  
K. R. Walley
Keyword(s):  
Nitric Oxide ◽  
Mean Arterial Pressure ◽  
Nitric Oxide Synthase ◽  
Arterial Pressure ◽  
Intact Animal ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Ventricular Contractility ◽  
Left Ventricular Contractility ◽  
Oxide Synthase

Decreased contractility of myocytes after cytokine exposure can be prevented by nitric oxide synthase inhibition. Whether this is true in an intact animal model of sepsis is unknown. Anesthetized pigs were pretreated with saline or a nitric oxide synthase inhibitor, N omega-nitro-L-arginine, and then treated with saline or endotoxin. We measured hemodynamics and left ventricular pressures (Millar catheter) and volumes (conductance catheter). Left ventricular contractility was assessed using the slope (E(max)) of the end-systolic pressure-volume relationship. Four hours after endotoxin infusion, E(max) had decreased by 44 +/- 5% (P < 0.05) and mean arterial pressure had decreased by 30 +/- 10% (P < 0.05). Pretreatment with N omega-nitro-L-arginine significantly reduced the decrease in E(max) to 28 +/- 3% (P < 0.05) and prevented the decrease in mean arterial pressure. However, it also raised pulmonary arterial pressure. We conclude that nitric oxide contributes to the early decrease in left ventricular contractility after endotoxin in the intact animal. However, the vascular effects of nitric oxide synthase inhibition increase right and left ventricular afterloads, which were detrimental to cardiac function.

Direct and reflexive effects of nitric oxide synthase inhibition on blood pressure

2008 ◽  
Vol 294 (1) ◽  
pp. H190-H197 ◽  
Author(s):  
Jill M. Wecht ◽  
Joseph P. Weir ◽  
David S. Goldstein ◽  
Annmarie Krothe-Petroff ◽  
Ann M. Spungen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Nitric Oxide Synthase ◽  
Arterial Pressure ◽  
Pressor Response ◽  
Control Group ◽  
Plasma Norepinephrine ◽  
Oxide Synthase

Direct effects of vasoactive substances on blood pressure can be examined in individuals with tetraplegia due to disruption of descending spinal pathways to sympathetic preganglionic neurons, as cervical lesions interfere with baroreceptor reflex buffering of sympathetic outflow. In this study, we assessed effects of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester (l-NAME) on mean arterial pressure, heart rate, and plasma norepinephrine concentrations in individuals with tetraplegia vs. effects shown in a neurologically intact control group. Seven individuals with tetraplegia and seven age-matched controls received, on separate visits and in the following order, placebo (30 ml normal saline) and 0.5, 1, 2, and 4 mg/kg l-NAME intravenously over 60 min. Supine hemodynamic data were collected, and blood was sampled at the end of each infusion and at 120, 180, and 240 min thereafter. l-NAME increased mean arterial pressure, and the relative increase was greater in the tetraplegia group than in the control group. Heart rate was reduced after l-NAME administration in both groups. l-NAME decreased plasma norepinephrine in the control group but not in the group with tetraplegia. These findings suggest that reflexive sympathoinhibition normally buffers the pressor response to nitric oxide synthase inhibition, an effect that is not evident in individuals with tetraplegia as a result of decentralized sympathetic vasomotor control.

Impact of Oxidative Stress on Maternal Serum Apelin 13 and Endothelial Nitric Oxide Synthase in Preeclampsia

2020 ◽  
Vol 13 (4) ◽  
pp. 2041-2048
Author(s):  
Rajeev Gandham ◽  
C.D. Dayanand ◽  
S.R. Sheela ◽  
Kiranmayee Pamidimukkala
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Mean Arterial Pressure ◽  
Nitric Oxide Synthase ◽  
Arterial Pressure ◽  
Pregnant Women ◽  
Endothelial Nitric Oxide Synthase ◽  
Maternal Serum ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Preeclampsia (PE) is the most common hypertensive disease of pregnancy, leads to maternal, perinatal morbidity and mortality, which accounts for 2-8% of pregnancies. Preeclampsia is characterized by new onset of hypertension and proteinuria after 20 weeks of gestation.The exact cause of preeclampsia is not clear. Aim of this study is to investigate the association between maternal serum apelin13, endothelial nitric oxide synthase, markers of oxidative stress in healthy pregnant women and preeclamptic women. This prospective study comprises 140 pregnant women consists of 70 preeclamptic women treated as cases and 70 nor motensive healthy pregnant women as controls. Five mL blood sample was collected, centrifuged to obtain serum/plasma and was stored at -80°C for further testing. Plasma was used for Ferric reducing antioxidant power (FRAP) assay and complete blood countwas done. Routine parameters like random blood sugar, renal profile, liver enzymes, lactate dehydrogenase (LDH), malondialdehyde (MDA), nitric oxide (NO), apelin 13 and endothelial nitric oxide synthase (eNOS)were also analyzed. Corresponding urine sample was tested for protein. Study results showed lower gestational age (36.99±3.48 weeks) and demographic details such as elevated blood pressure [systolic (156.80±13.71 mmHg),diastolic (101.97±10.70 mmHg),and mean arterial pressure (120.88±11.02 mmHg)], BMI (27.42±3.80 kg/m2) and pulse rate (87.68±5.74 bpm) were observed in cases than controls. The biological markers namely serum MDA (18.57±7.52μmoles/L) levels were significantly increased and nitric oxide (6.47±1.22μmoles/L), FRAP (1292.10±525.38 mmol/L), apelin 13(312.42±189.00pg/ml) andeNOS(5.07±2.30 ng/ml)levels were significantly decreased in cases.Mean arterial pressure was negatively correlatedwithApelin 13 (r=-0.179), NO (r=-0.065), FRAP (r=-0.169), and birth weight (r=-0.281) and eNOS (r= 0.013), MDA (r= 0.022) were positively correlated with mean arterial pressure. The study concludes that reduced levels of apelin 13, eNOS, FRAP,NO and high oxidative stress, contribute to pathogenesis of preeclampsia and adverse perinatal outcome. It also demands sufficient evidence for the functional role of apelin 13 as a target in hypertension regulation.

scholarly journals Effect of Blockade of Nitric Oxide Synthesis on the Renin Secretory Response to Frusemide in Conscious Rabbits

1995 ◽  
Vol 88 (6) ◽  
pp. 657-663 ◽  
Author(s):  
Ian A. Reid ◽  
Lance Chou
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Nitric Oxide Synthase ◽  
Arterial Pressure ◽  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Macula Densa ◽  
Renin Secretion ◽  
Oxide Synthase

1. The enzyme nitric oxide synthase is present in the macula densa and may participate in the control of renin secretion by the adjacent juxtaglomerular cells. In the present study, we investigated the effect of inhibiting nitric oxide synthase on the renin secretory response to frusemide, which stimulates renin secretion by blocking Na+-K+-2Cl− co-transport in the macula densa. 2. Injection of frusemide in 12 conscious rabbits elicited a transient increase in mean arterial pressure from 84 ± 2 to 92 ± 3 mmHg at 5 min (P < 0.01) and a sustained increase in heart rate from 246 ± 6 to 281 ± 10 beats/min at 45 min (P < 0.01). Plasma renin activity increased from 8.0 ± 1.2 to 14.3 ± 1.8, 12.4 ± 1.6 and 11.6 ± 1.5 pmol 2 h−1 ml−1 at 15, 30 and 45 min respectively (P < 0.01). There were no changes in plasma sodium and potassium concentrations or osmolality. 3. Inhibition of nitric oxide synthase with NG-nitro-l-arginine methyl ester increased mean arterial pressure by 9 mmHg, decreased heart rate and plasma renin activity, and markedly suppressed the renin response to frusemide (from 4.6 ± 0.7 to 7.6 ± 1.7, 4.7 ± 1.0 and 4.6 ± 0.7 pmol 2 h−1 ml−1 at 15, 30 and 45 min respectively). By contrast, infusion of an equipressor dose of phenylephrine did not suppress the renin response to frusemide. 4. Histochemical studies with the NADPH diaphorase technique confirmed the presence of nitric oxide synthase in the macula densa, and suggested that enzyme activity is increased by treatment with frusemide. 5. These results are consistent with a role for the l-arginine—nitric oxide pathway in the modulation of renin secretion by the macula densa.

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.

Endothelium-derived nitric oxide mediates hypoxic vasodilation of resistance vessels in humans

1996 ◽  
Vol 271 (3) ◽  
pp. H1182-H1185 ◽  
Author(s):  
M. L. Blitzer ◽  
S. D. Lee ◽  
M. A. Creager
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Vascular Resistance ◽  
Forearm Blood Flow ◽  
Vasodilator Response ◽  
Healthy Humans ◽  
Resistance Vessels ◽  
Oxide Synthase ◽  
Forearm Vascular Resistance

Endothelium-derived nitric oxide (EDNO) contributes to basal systemic vascular resistance under normoxic conditions. The purpose of this investigation was to determine whether EDNO contributes to the regulation of limb vascular resistance during hypoxia in healthy humans. Forearm blood flow was assessed by venous occlusion plethysmography. Hypoxia was induced by delivering a mixture of N2 and O2 via a gas blender adjusted to reduce the PO2 to 50 mmHg. During hypoxia, forearm blood flow increased from 2.4 +/- 0.2 to 3.0 +/- 0.3 ml.100 ml-1.min-1 (P < 0.001), and forearm vascular resistance decreased from 38 +/- 3 to 29 +/- 3 units (P < 0.001). The nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 2,000 micrograms/min intra-arterially) was administered to eight subjects. The percent increase in forearm vascular resistance after administration of L-NMMA was greater during hypoxia than normoxia (67 +/- 14 vs. 39 +/- 15%, P < 0.05). L-NMMA reduced the forearm vasodilator response to hypoxia from 27 +/- 3 to 11 +/- 5% (P = 0.01). To exclude the possibility that this attenuated response to hypoxia was a consequence of vasoconstriction and not specific for nitric oxide synthase inhibition, six subjects received intra-arterial phenylephrine. Phenylephrine did not affect the vasodilator response to hypoxia (17 +/- 3 vs. 21 +/- 6%, P = NS). It is concluded that EDNO contributes to hypoxia-induced vasodilation in the forearm resistance vessels in healthy humans.

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