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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A deficiency of nitric oxide may be responsible for the increased vascular resistance associated with human essential hypertension and that seen in animal models of hypertension. Premenopausal females are relatively protected from hypertension and cardiovascular complications. Levels of superoxide can influence the availability of nitric oxide. We hypothesize that there are differences in nitric oxide availability between stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) and that superoxide may be responsible for at least some of these differences. We studied vascular reactivity in endothelium-intact aortic rings from WKY and SHRSP. We measured nitric oxide synthase activity in endothelial cells removed from aortas and also measured circulating nitrite/nitrate levels. We found the response to N(G)-nitro-L-arginine methyl ester to be significantly greater in WKY compared with SHRSP (95% CI: 20 to 174; P=.015) and in females compared with males in WKY (95% CI: 143 to 333; P=.00004) and SHRSP (95% CI: 70 to 224; P=.0006). Endothelial nitric oxide synthase activity was significantly greater in SHRSP compared with WKY (95% CI: 2.3 to 17.6; P=.016). The EC50 for relaxation to carbachol was significantly greater in male rats compared with female rats (95% CI: -1.1 to -0.2; P=.003) within the SHRSP strain. The maximum relaxation to carbachol was significantly attenuated in stroke prone spontaneously hypertensive compared with Wistar-Kyoto rats (95% CI: 1.7 to 14.4; P=.015). Diethyldithiocarbamate had a significantly greater effect on the stroke prone spontaneously hypertensive rats' carbachol response than that of Wistar-Kyoto rats (95% CI: 14.3 to 47.0; P=.0008). We conclude that superoxide may be responsible for strain differences in vascular reactivity, whereas nitric oxide availability may be responsible for sex differences independently of endothelial nitric oxide synthase activity and superoxide.
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PMID:Sex differences in the abundance of endothelial nitric oxide in a model of genetic hypertension. 940 76

Patients with atrial fibrillation have been reported to exhibit abnormal hemostasis. Since nitric oxide (NO) exerts antithrombotic effects and attenuates platelet function, we evaluated two indicators of plasma NO levels, the plasma levels of nitrite and nitrate (NOx), and the levels of cGMP in platelets. We also examined whether indicators of plasma NO levels were associated with abnormalities in parameters related to platelet function, blood coagulation, and fibrinolysis. We evaluated 45 patients with chronic sustained atrial fibrillation (33 men and 12 women, age range 63 +/- 2 years) compared with 45 sex- and age- (+/- 2 years) matched nonhospitalized subjects with sinus rhythm. There were no significant differences between the two groups in the incidence of risk factors for stroke except for ischemic heart disease or in echocardiographic parameters. Plasma levels of NOx measured using the Greiss reagent (mean [interquartile range]: 15.6 [9.5 to 25.7] versus 24.1 [14.2 to 40.8] mumol/L, n = 45) and the platelet cGMP levels (0.33 [0.16 to 0.67] versus 0.63 [0.31 to 1.29] pmol/10(9) platelets, n = 9) were significantly (P < .05) lower in the patients with atrial fibrillation than in the control subjects. Plasma levels of D-dimer, beta-thromboglobulin, and fibrinogen were significantly (P < .05) higher in the patients with atrial fibrillation. The two groups did not differ as to the plasma levels of tissue plasminogen activator or plasminogen activator inhibitor-1. Our findings suggest that a decrease in plasma NO levels may account for the hemostatic abnormalities observed in patients with atrial fibrillation.
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PMID:Plasma levels of nitrite/nitrate and platelet cGMP levels are decreased in patients with atrial fibrillation. 940 10

The relationship between plasma nitrite, nitrate, and nitric oxide (NOx), cytokines, and cardiac and vascular dysfunction after lipopolysaccharide (LPS) was studied in chronically instrumented anesthetized dogs. LPS was administered (1 mg/kg i.v.), and hemodynamics were recorded at baseline, every 15 min for 1 h, and every hour for an additional 14 h. Dramatic reductions in mean arterial pressure (-48 +/- 6%), cardiac output (-40 +/- 8%), stroke volume (-42 +/- 9%), and first derivative of left ventricular pressure (LV dP/dt, -38 +/- 7%) were seen within 1 h after injection of endotoxin. Cardiac output was not different from control by 9 h, whereas mean arterial pressure (-19 +/- 7%), stroke volume (-32 +/- 8%), and LV dP/dt (-21 +/- 10%) remained significantly depressed from control. Total peripheral resistance was not significantly different from control. Therefore, the hypotension appears to be due to a reduction in cardiac function and not to vasodilation. Levels of plasma NOx were not different from control until 4 h after LPS reached levels 597 +/- 126% higher than control at 15 h. In vitro production of nitrite by coronary microvessels was also elevated, supporting our in vivo findings. In contrast, production of tumor necrosis factor-alpha and interleukin-6 occurred shortly after endotoxin injection, reaching peak levels at 45 and 150 min, respectively. Our data suggest that inducible nitric oxide synthase induction occurred after LPS injection. It is unlikely that nitric oxide contributed significantly to the hypotension and cardiac dysfunction early in our study, whereas cardiodepressive cytokines, particularly tumor necrosis factor-alpha, may be important. In contrast, the hemodynamic effects seen late after injection of endotoxin may be the result of an overproduction of nitric oxide, since there was a sixfold increase in plasma NOx levels at this time and a marked production of nitric oxide in isolated coronary microvessels in vitro.
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PMID:Relationship between plasma NOx and cardiac and vascular dysfunction after LPS injection in anesthetized dogs. 945 68

We hypothesized that plasma nitric oxide (NO), generated via inducible NO synthase (iNOS) or endothelial constitutive NO synthase and measured via its by-products NO2- and NO3- (NO2- + NO3- = NOx) would increase and remain elevated during chronic peritoneal sepsis. We further hypothesized that treatment with aminoguanidine (AG; 50 mg/kg), a selective iNOS inhibitor, would decrease NO production and alter blood flow. Sprague Dawley rats were randomized to septic and nonseptic groups. Septic rats received an intraperitoneal cecal slurry (200 mg of cecal material/5 mL 5% dextrose-H2O/kg); control rats received sterile 5% dextrose-H2O (5 mL/kg) only. Plasma NOx and hemodynamics were measured 0, 4, 12, 24, and 48 h after sepsis or sham induction. We also examined the effect of AG, an iNOS inhibitor, on plasma NOx levels and tissue blood flow at 24 h. Septic rats uniformly displayed signs of sepsis, including lethargy, piloerection, and diarrhea. NOx levels were significantly elevated compared with controls at 4, 12, 24, and 48 h (p < or = .05). Septic rats also demonstrated hypotension (t = 12, 24, and 48 h) and tachycardia (t = 4, 12, 24, and 48 h). The infusion of AG (50 mg/kg intravenously for 30 min) at 24 h significantly decreased plasma NOx in septic animals. Plasma NOx concentrations returned to basal levels by 90 min after infusion of AG. In addition, blood flow studies demonstrated that AG treatment in nonseptic rats resulted in a significant decrease in blood flow to the stomach, skin, and adipose tissue, whereas AG infusion did not significantly alter the regional perfusion profile in septic animals. Furthermore, treatment with AG did not significantly alter mean arterial pressure in either group; however, nonseptic animals exhibited a decrease in stroke volume, and septic animals demonstrated an increase in heart rate. In contrast to the rise and fall of NOx levels in endotoxemia, this study demonstrates that the initial rise is sustained during 48 h of peritoneal sepsis. This sustained increase in NOx levels in this model correlated with the observable signs of systemic infection and may relate to enhanced iNOS activity. AG infusion demonstrated variable effects on regional tissue blood flow profiles in septic and nonseptic animals and attenuated the increase in plasma NOx levels in septic animals, an index of iNOS activity.
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PMID:Effect of aminoguanidine on plasma nitric oxide by-products and blood flow during chronic peritoneal sepsis. 956 58

We investigated the effects of N(omega)-monomethyl-L-arginine (L-NMMA) and fluid loading on tumor necrosis factor (TNF)-induced cardiovascular dysfunction in awake dogs. L-NMMA (40 mg x kg(-1) given intravenously over a period of 10 min, and followed by dosing at 40 mg x kg(-1) x h(-1) for 6 h) and TNF (20 or 45 microg x kg(-1) given intravenously for 20 min), given alone or in combination, significantly decreased stroke volume, cardiac index, oxygen delivery, and left-ventricular (LV) function plots over a period of 6 h. Of note was that the cardiac-depressant effects of TNF and L-NMMA given together were significantly less than additive. Thus, the combination was beneficial (or significantly less harmful to cardiac performance than expected), possibly because L-NMMA augmented cardiac preload as shown by significant increases in both pulmonary capillary wedge pressure (PCWP) and central venous pressure (CVP). Fluid challenges at 6 h (Ringer's solution at 80 ml x kg(-1) given over a period of 30 min) also significantly increased PCWP and CVP, and abolished the beneficial preload effect of L-NMMA on cardiac performance. Thus, after fluid loading, the cardiac-depressant effects of TNF and L-NMMA given together became equal to the sum of those produced by TNF and L-NMMA given separately. Although L-NMMA significantly decreased serum nitrite/nitrate levels, TNF did not increase these end products of nitric oxide (NO) production relative to controls. Therefore, after preload abnormalities were eliminated with fluid loading, L-NMMA had no beneficial effect on TNF-induced cardiac depression, and TNF did not increase end products of NO production. These findings are not consistent with NO being the mechanism of TNF-induced acute cardiac depression.
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PMID:Effects of L-NMMA and fluid loading on TNF-induced cardiovascular dysfunction in dogs. 960 14

Thrombotic potential and hemodynamic changes were assessed in the cerebral microcirculation in normal rats (WKY), non-stroke-prone spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP) at the age of 4, 16 and 32 weeks. Whole blood platelet aggregation revealed that the platelet aggregability in vitro was significantly depressed in SHRSP compared to WKY at 16 and 32 weeks using 2 microg/ml collagen but was similar or higher than WKY at 32 weeks using 20 or 40 microg/ml collagen. Platelet-rich thrombi were induced using a helium-neon (He-Ne) laser technique in vivo. The numbers of laser pulses required to induce an occlusive thrombus in arterioles were similar in the three strains at the age of 4 weeks. In contrast, the numbers of laser pulses needed to induce vascular occlusion in SHR (5.5 +/- 0.7; n = 4) and SHRSP (4.9 +/- 0.3; n = 4) were lower than in WKY (7.4 +/- 0.3; n = 5) at the age of 16 weeks. Similar differences were observed at 32 weeks (SHR 5.8 +/- 0.2; n = 6; SHRSP 4.3 +/- 0.1; n = 4; WKY 7.0 +/- 0.2; n = 7). Red blood cell velocities were measured in pial arterioles using a fiber-optic laser Doppler anemometer microscope. Red cell velocities and wall shear rates in SHR and SHRSP were significantly lower than those in WKY (p < 0.05) at the age of 16 weeks and were markedly lower in SHRSP than in either WKY or SHR at the age of 32 weeks. The plasma concentration of nitrite/nitrate determined by the Griess reaction was significantly reduced in SHRSP at 32 weeks compared with 4-week-old rats. These changes could contribute to the enhanced tendency to cerebrovascular stroke in SHRSP.
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PMID:Enhanced thrombogenicity and altered hemodynamics in the cerebral microvasculature of stroke-prone spontaneously hypertensive rats. 969 Apr 82

Among cardiovascular diseases, hypertension, angina pectoris, acute myocardial infarction and ischemic stroke present a circadian pattern with a greater incidence of unfavourable events between awakening and noon. Chronotherapy aims to use drugs that release their active principles at different times during the day, according to biological needs. In chronotherapy of cardiovascular diseases, a particular attention has been paid to slow-release drugs that assure a 24 hours therapeutic effect with once a day administration. In primary hypertension well controlled by monotherapy (dipper hypertensives), the morning administration of long-acting beta-blockers and calcium antagonists has shown to control blood pressure over 24 hours, whereas ACE-inhibitors have proved more effective when administered at evening. In secondary hypertension (non dipper hypertensives) the administration of calcium antagonists is more effective at evening. Patients with severe hypertension need polytherapy. In that case, at least one of the antihypertensive drugs should be given at evening to lower night blood pressure values, which are particularly elevated also during sleep, and so to prevent an excessive blood pressure rise on awakening. In chronic monotherapy of ischemic heart disease, long-acting beta-blockers and calcium antagonists have shown to be equally effective when they are administered at morning, whereas slow-release nitrates, which need a nitrate-free interval, are to be administered either at morning or at evening, according to the expected time of onset of anginal pain. ASA seems to reduce the morning incidence of acute myocardial infarction, while tissue-type plasminogen activator presents a circadian variation of its thrombolytic activity with a higher efficacy between noon and midnight.
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PMID:[Application of chronotherapy to cardiovascular diseases]. 979 79

The anti-inflammatory role of nitric oxide (NO) was studied in a model of hepatic ischemia-reperfusion (I/R) in rats. Male Fischer rats were subjected to 30 min of no-flow ischemia of the left and median lobes of the liver, and animals were examined for a 4-h period of reperfusion. The animals were divided into the following groups: control-vehicle; I/R-vehicle; I/R-Nomega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg iv, 10 min before reperfusion); sham control-L-NAME, and I/R-S-nitroso-N-acetyl-penicillamine (SNAP, 25 micromol/kg iv, 10 min before reperfusion, followed by 20 micromol. kg-1. h-1 in 1.0 ml saline infused for 4 h). Results showed that mean arterial blood pressure was significantly increased in the sham control-L-NAME or I/R-L-NAME groups compared with either the I/R-vehicle or I/R-SNAP groups. However, cardiac index (CI) and stroke volume index (SVI) were markedly decreased, and systemic vascular resistance index (SVRI) was dramatically increased. Interestingly, the CI and SVI in rats treated with SNAP were markedly improved over that of the I/R group. Plasma nitrate and nitrite levels were significantly decreased in the I/R-L-NAME group; however, superoxide generation in the ischemic lobes and plasma alanine aminotransferase activity were higher compared with I/R-SNAP rats. The L-NAME-induced enhancement of hepatic injury in rats with I/R may be due in part to neutrophil infiltration, which was significantly increased compared with animals subjected to I/R or I/R-SNAP. The mechanism of L-NAME-enhanced neutrophil infiltration may be due to the fact that the ratios of P-selectin and intercellular adhesion molecule 1 (ICAM-1) mRNA to glyceraldehyde-3-phosphate dehydrogenase mRNA extracted from the ischemic lobes of I/R-L-NAME rats were significantly increased when compared with the I/R-SNAP group. These results suggest that 1) endogenous NO reduces the SVRI and permits an increased CI and SVI; 2) exogenous NO further improves CI and SVI; and 3) endogenous, but not exogenous, NO decreases P-selectin and ICAM-1 mRNA expression, thereby reducing polymorphonuclear neutrophil-dependent reperfusion tissue injury.
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PMID:NO modulates P-selectin and ICAM-1 mRNA expression and hemodynamic alterations in hepatic I/R. 984 19

The pharmacologic profiles of nicorandil in the cardiovascular system have been characterized by K-channel opening and nitrate activities. However, the effects of nicorandil on acute heart failure have yet to be elucidated. To investigate the effects of nicorandil under such pathophysiologic conditions, we administered nicorandil intravenously to dogs with acute ischemic heart failure induced by coronary embolization and compared the results with those induced by cromakalim and nitroglycerin. The heart failure in this experiment was demonstrated by a reduction of mean blood pressure (MBP) from 143+/-3 to 129+/-2 mm Hg (p < 0.01); cardiac output (CO) from 2.18+/-0.10 to 1.06+/-0.05 L/min (p < 0.01); stroke volume (SV) from 12.7+/-0.6 to 6.8+/-0.3 ml/min (p < 0.01); Vmax, an index of the contractility of the left ventricle, from 105.5+/-4.4 to 49.9+/-1.8 1/s (p < 0.01), and an increase in right atrial pressure (RAP) from 2.9+/-0.3 to 5.3+/-0.3 mm Hg (p < 0.01); left ventricular end-diastolic pressure (LVEDP) from 2.5+/-0.4 to 26.0+/-1.4 mm Hg (p < 0.01); and T, time constant of left ventricular relaxation, from 38.3+/-0.8 to 62.4+/-2.8 ms (p < 0.01). Furthermore, plasma renin activity (PRA) and plasma atrial natriuretic peptide (ANP) increased (from 1.72+/-0.29 to 5.03+/-0.68 ng AngI/ml/h, p < 0.01; from 103.9+/-5.8 to 411.5+/-29.4 pg/ml, p < 0.01, respectively), whereas brain natriuretic peptide (BNP) remained unchanged (from 23.1+/-2.2 to 26.9+/-1.4 pg/ml). Nicorandil (10-40 microg/kg/min, i.v. infusion for 20 min for each dosing) or cromakalim (0.25-1 microg/kg/min) decreased MBP, systemic vascular resistance (SVR), RAP, and LVEDP, and increased CO, SV, and Vmax. However, the reduction of RAP in cromakalim was significantly smaller than those of nicorandil and nitroglycerin in comparison at similar hypotensive doses. Nitroglycerin (2.5-10 microg/kg/min) decreased MBP, RAP, and LVEDP, and increased Vmax but did not change CO or SV. Increased plasma ANP levels, an index of cardiac filling pressure after induction of acute ischemic heart failure, were decreased significantly by cromakalim and tended to decrease by nicorandil or nitroglycerin. Plasma BNP levels and PRA were not influenced by any of these drugs. These results suggest that nicorandil produces the reduction of both preload and afterload followed by an improvement of cardiac contractility in this model. The increase in CO may be mediated mainly by the drug's K-channel opening activities and the reduction of venous tone by its nitrate properties. Nicorandil may prove to be useful in the treatment of acute ischemic heart failure.
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PMID:Hemodynamic and hormonal responses to nicorandil in a canine model of acute ischemic heart failure: a comparison with cromakalim and nitroglycerin. 989 Apr 2

1. We recently developed a new technique for measuring serum NO2 and NO3 levels precisely, and we examined these parameters in severely brain-injured ICU patients who could not take nutrition intestinally. 2. Our results demonstrated that NO increased rapidly after stroke, trauma, and the occurrence of infection in all ICU patients. Elevation of NO2/NO3 was most pronounced 24 to 48 hr after trauma or ischemic stroke. This dysregulation of free radical elimination closely correlated with hemoglobin levels. 3. In most ICU patients, with the exception of those with complications of infection, the free radical potentials were maximal at 24 to 48 hr and continued to remain high for 4 to 5 days after trauma or stroke. The level of free radical potentials was closely correlated with the severity and prognosis of critically injured patients. None with radical potential values higher than 0.4 microM survived. 4. Clinically, the maintenance of hemoglobin at > 12 g/dl and lower body temperature were demonstrated to be successful in the management of these free radical reactions.
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PMID:Application of a novel technique for clinical evaluation of nitric oxide-induced free radical reactions in ICU patients. 1007 61


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