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PubMedDate not supplied

Interstitial pulmonary edema.

Florid pulmonary edema is frequently preceded by interstitial edema formation. Because of alterations in the balance of oncotic and hydrostatic pressures between the capillary and lung interstitium or changes in capillary permeability, edema fluid forms in the interstitial spaces of the lung. Once the capacitance of the pulmonary lymphatics is exceeded, interstitial and alveolar edemas become more prominent. Bronchoconstriction and increased vascular resistance lead to ventilation-perfusion imbalance, reduced lung compliance, and increasing symptoms. Early detection is possible by noting characteristic changes in gas exchange and chest radiograph. Awareness and early recognition of these changes, together with the predisposing clinical settings, can lead to the institution of appropriate therapy before patients become severely ill with frank alveolar pulmonary edema.

Humans↗
PubMed1990

Effects of a potassium-sparing/thiazide diuretic combination on cardiovascular reactivity to vasopressor agents.

The vascular effects of a diuretic combination (spironolactone/altizide) were studied in 5 anuric patients undergoing dialysis by measuring changes in cardiovascular reactivity to norepinephrine (NE) and angiotensin II (AII) after infusion of incremental doses of these 2 vasopressor agents. There was a marked dose-response relation between NE and AII administration and mean (NE) or diastolic (AII) blood pressure (BP). Diuretic treatment moderated the increase in mean or diastolic BP induced by NE or AII. In addition, the pressor doses of NE and AII, which are also parameters of vascular reactivity, were significantly increased after diuretic treatment (NE, +101%; AII, +163%). Right atrial and pulmonary capillary wedge pressures increased along with BP in response to NE. Diuretic treatment also moderated the increase in right atrial and pulmonary capillary wedge pressures induced by NE. These results suggest that the antihypertensive action of spironolactone and altizide in combination is mainly due to a direct effect on resistance and capacitance vessels. The mechanisms by which diuretics modify the cardioreactivity remain poorly understood; however, they may modify electrolyte transport (sodium and calcium) across vascular smooth muscle cell membranes or stimulate prostaglandin release.

Angiotensin II↗
PubMed1993

The effects of N omega-nitro-L-arginine methyl ester, sodium nitroprusside and noradrenaline on venous return in the anaesthetized cat.

1. The vascular actions of N omega-nitro-L-arginine methyl ester (L-NAME), sodium nitroprusside and noradrenaline were investigated in cats under chloralose anaesthesia with controlled vascular tone and ventilation. Cardiac output, heart rate, vascular pressures and mean circulatory filling pressure (MCFP) were measured. Total peripheral resistance (TPR) and resistance to venous return (Rvr) were calculated from steady-state readings. 2. L-NAME (37 mumol kg-1, i.v.) administered to ten cats receiving noradrenaline (6 nmol kg-1 min-1, i.v.) increased aortic pressure by 47.5 +/- 7.1 mmHg from 106 mmHg, and MCFP by 1.56 +/- 0.36 mmHg from 10.0 mmHg (means +/- s.e. means). Mean changes in portal venous pressure, RAP and heart rate were not significant. Cardiac output fell by 29.7 +/- 3.3% from 130 ml min-1 kg-1. TPR rose by 108 +/- 7.2% from 796 mmHg l-1 min kg and Rvr by 58.4 +/- 4.5% from 64 mmHg l-1 min kg. 3. Infusion of sodium nitroprusside into cats receiving noradrenaline evoked dose-related falls in aortic pressure, MCFP, TPR and Rvr. Changes in portal venous pressure, RAP and heart rate were not significant and cardiac output fell slightly. After L-NAME, sensitivity to nitroprusside was increased by 139 +/- 34% for MCFP, 176 +/- 19% for TPR and 351 +/- 39% for Rvr, and cardiac output rose slightly. The nitroprusside infusion required to restore TPR after L-NAME was estimated to be 5.8 x 10(+/- 0.41) nmol kg-1 min-1, which was approximately three times more than that required to restore MCFP. 4. Infusion of noradrenaline evoked dose-related increases in aortic and portal venous pressures, heart rate, cardiac output, MCFP, TPR and Rvr. After L-NAME and nitroprusside (4.4 nmol kg-1 min-1, i.v.),TPR and Rvr were not significantly different, but MCFP was reduced by 1.76 +/- 0.24 mmHg, and cardiac output by 22 +/- 1.9%. After subsequent expansion of the circulating blood volume (5-7.5 ml kg-1 dextran-saline), mean values for all parameters were restored to their previous levels. Sensitivity to noradrenaline was not significantly altered for heart rate, TPR and Rvr but was reduced by 31.8 +/- 12%for MCFP and by 66.5 +/- 18% for cardiac output.5. The depression of cardiac output by L-NAME is attributed to the increase in Rvr, partly compensated by the rise in MCFP. For a given rise in MCFP, the increase in R, was seven times greater after L-NAME than after noradrenaline, and the difference in the relative actions of the two drugs on resistance and capacitance vessels largely accounts for their contrasting effects on venous return. A procedure is suggested for replacement of vascular nitric oxide by nitroprusside infusion and blood volume expansion.

Anesthesia↗
PubMed2005

Different phospholipase-C-coupled receptors differentially regulate capacitative and non-capacitative Ca2+ entry in A7r5 cells.

Several receptors, including those for AVP (Arg8-vasopressin) and 5-HT (5-hydroxytryptamine), share an ability to stimulate PLC (phospholipase C) and so production of IP3 (inositol 1,4,5-trisphosphate) and DAG (diacylglycerol) in A7r5 vascular smooth muscle cells. Our previous analysis of the effects of AVP on Ca2+ entry [Moneer, Dyer and Taylor (2003) Biochem. J. 370, 439-448] showed that arachidonic acid released from DAG stimulated NO synthase. NO then stimulated an NCCE (non-capacitative Ca2+ entry) pathway, and, via cGMP and protein kinase G, it inhibited CCE (capacitative Ca2+ entry). This reciprocal regulation ensured that, in the presence of AVP, all Ca2+ entry occurred via NCCE to be followed by a transient activation of CCE only when AVP was removed [Moneer and Taylor (2002) Biochem. J. 362, 13-21]. We confirm that, in the presence of AVP, all Ca2+ entry occurs via NCCE, but 5-HT, despite activating PLC and evoking release of Ca2+ from intracellular stores, stimulates Ca2+ entry only via CCE. We conclude that two PLC-coupled receptors differentially regulate CCE and NCCE. We also address evidence that, in some A7r5 cells lines, AVP fails either to stimulate NCCE or inhibit CCE [Brueggemann, Markun, Barakat, Chen and Byron (2005) Biochem. J. 388, 237-244]. Quantitative PCR analysis suggests that these cells predominantly express TRPC1 (transient receptor potential canonical 1), whereas cells in which AVP reciprocally regulates CCE and NCCE express a greater variety of TRPC subtypes (TRPC1=6>2>3).

Animals↗
PubMed1999

Possible involvement of Ca2+ entry and its pharmacological characteristics responsible for endothelium-dependent, NO-mediated relaxation induced by thapsigargin in guinea-pig aorta.

Thapsigargin, a specific inhibitor of Ca(2+)-pump Ca(2+)-ATPase in the sarcoplasmic/endoplasmic reticulum (SR/ER), produces an endothelium-dependent vascular relaxation. In the present study, pharmacological features of thapsigargin-induced endothelium-dependent relaxation were functionally characterized in the isolated guinea-pig aorta especially focusing on the Ca2+ mobilization mechanisms in endothelial cells. Thapsigargin-induced endothelium-dependent vascular relaxation was markedly suppressed by N(G)-nitro-L-arginine (L-NNA) and calmidazolium, suggesting that the vascular relaxation to thapsigargin is largely attributable to endothelium-derived nitric oxide (NO) produced as a result of the activation of Ca2+, calmodulin-dependent NO synthase (NOS). Removal of Ca2+ from the external solution abolished the endothelium-dependent relaxation of guinea-pig aorta in response to thapsigargin. Thapsigargin-induced endothelium-dependent relaxation was inhibited more strongly compared with the endothelium-independent relaxation to an NO donor, SIN-1 (3-(4-morpholinyl)-sydnonimine), when the artery preparation was preconstricted with a high concentration (80 mM) of KCl instead of agonistic stimulation. Endothelium-dependent relaxation induced by thapsigargin was not affected by diltiazem, a blocker of L-type voltage-gated Ca2+ channels. SK&F96365 (1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1 H-imidazole) and Ni2+, both of which block capacitative Ca(2+) entry, did not show any appreciable inhibitory effects on the endothelium-dependent relaxation to thapsigargin. These findings suggest that in guinea-pig aorta, endothelium-dependent NO-mediated relaxation induced by thapsigargin is preceded by the increase in the cytosolic free Ca2+ concentrations ([Ca2+]cyt) following the depletion of stored Ca2+ in thapsigargin-sensitive store sites in endothelial cells. Although the increase in [Ca2+]cyt responsible for the activation of endothelium NOS leading to thapsigargin-induced vascular relaxation may be ascribed to the capacitative Ca2+ entry from extracellular space, the Ca2+ entry mechanism stimulated with thapsigargin is deficient in sensitivity to SK&F96365 and Ni2+ in the endothelium of guinea-pig aorta.

Animals↗
PubMed1981

[Changes in diameters of small pulmonary venous and arterial vessels after nitroglycerin (author's transl)].

Diameters of the small arterial and venous pulmonary vessels were studied in 17 patients, using selective pulmonary angiography. The majority had coronary heart disease. Pulmonary and systemic hemodynamics were also evaluated. In 11 patients, these procedures were repeated 3 minutes after the sublingual administration of 1.6 mg of nitroglycerin (Group I). The remaining 6 patients served as controls (Group II). In Group I, pulmonary circulatory pressures, left ventricular filling pressure, and pulmonary vascular resistance declined significantly compared with Group II. The diameters of the small pulmonary veins declined by more than 10 percent in Group I while remaining constant in Group II. Differences between the two groups in terms of the response of the small arterial vessels was less evident. Increases in vessel cross-sectional area were observed despite considerably reduced intravascular pressure. The increase in elasticity and capacitance of the pulmonary vessels following nitroglycerin is more pronounced on the venous than on the arterial side. These findings suggest that the pulmonary vascular bed contributes significantly to the therapeutically important pooling effect caused by nitroglycerin in the treatment of angina pectoris and pulmonary edema.

Coronary Disease↗
PubMed2002

Impaired pulmonary artery contractile responses in a rat model of microgravity: role of nitric oxide.

Vascular contractile hyporesponsiveness is an important mechanism underlying orthostatic intolerance after microgravity. Baroreceptor reflexes can modulate both pulmonary resistance and capacitance function and thus cardiac output. We hypothesized, therefore, that pulmonary vasoreactivity is impaired in the hindlimb-unweighted (HLU) rat model of microgravity. Pulmonary artery (PA) contractile responses to phenylephrine (PE) and U-46619 (U4) were significantly decreased in the PAs from HLU vs. control (C) animals. N(G)-nitro-L-arginine methyl ester (10(-5) M) enhanced the contractile responses in the PA rings from both C and HLU animals and completely abolished the differential responses to PE and U4 in HLU vs. C animals. Vasorelaxant responses to ACh were significantly enhanced in PA rings from HLU rats compared with C. Moreover, vasorelaxant responses to sodium nitroprusside were also significantly enhanced. Endothelial nitric oxide synthase (eNOS) and soluble guanlyl cyclase expression were significantly enhanced in PA and lung tissue from HLU rats. In marked contrast, the expression of inducible nitric oxide synthase was unchanged in lung tissue. These data support the hypothesis that vascular contractile responsiveness is attenuated in PAs from HLU rats and that this hyporesponsiveness is due at least in part to increased nitric oxide synthase activity resulting from enhanced eNOS expression. These findings may have important implications for blood volume distribution and attenuated stroke volume responses to orthostatic stress after microgravity exposure.

Animals↗
PubMed1982

Body fluid homeostasis in congestive heart failure and cirrhosis with ascites.

The urinary excretion of salt and water in man is regulated by a variety of renal and extrarenal mechanisms that respond to changes in dietary sodium intake as well as to alterations in the holding capacity of the vascular and interstitial compartments. Changes in extracellular fluid volume are detected by volume sensors located in the intrathoracic vascular bed, the kidney and other organs. These sensing mechanisms gauge the adequacy of intravascular volume relative to capacitance at various sites within the circulation. Congestive heart failure and cirrhosis with ascites are two disease states of man in which a hemodynamic disturbance within a given circulatory subcompartment is perceived by these sensing mechanisms and results in renal sodium retention. While the primary disturbance in both of these conditions originates outside the kidney, a variety of renal effector mechanisms respond to the perceived circulatory disturbance and result in enhanced tubule reabsorption of salt and water. These effector mechanisms involve physical adjustments in renal microvascular hemodynamics, tubule fluid composition and flow rate and transtubular ion gradients. These in turn are partially regulated by a variety of neural and humoral pathways including the renin-angiotensin-aldosterone axis, prostaglandins, and kinins.

Aldosterone↗
PubMed1993

bpshape wk4: a computer program that implements a physiological model for analyzing the shape of blood pressure waveforms.

We describe the theory and computer implementation of a newly-derived mathematical model for analyzing the shape of blood pressure waveforms. Input to the program consists of an ECG signal, plus a single continuous channel of peripheral blood pressure, which is often obtained invasively from an indwelling catheter during intensive-care monitoring or non-invasively from a tonometer. Output from the program includes a set of parameter estimates, made for every heart beat. Parameters of the model can be interpreted in terms of the capacitance of large arteries, the capacitance of peripheral arteries, the inertance of blood flow, the peripheral resistance, and arterial pressure due to basal vascular tone. Aortic flow due to contraction of the left ventricle is represented by a forcing function in the form of a descending ramp, the area under which represents the stroke volume. Differential equations describing the model are solved by the method of Laplace transforms, permitting rapid parameter estimation by the Levenberg-Marquardt algorithm. Parameter estimates and their confidence intervals are given in six examples, which are chosen to represent a variety of pressure waveforms that are observed during intensive-care monitoring. The examples demonstrate that some of the parameters may fluctuate markedly from beat to beat. Our program will find application in projects that are intended to correlate the details of the blood pressure waveform with other physiological variables, pathological conditions, and the effects of interventions.

Animals↗
PubMed1978

Hemodynamic effects of nitroprusside and hydralazine in experimental cardiac tamponade.

Cardiac tamponade is associated with decreased cardiac output and increased systemic vascular resistance. Thus, vasodilator drugs might lower systemic resistance and increase cardiac output. Three groups of dogs were studied during tamponade. Group I received nitroprusside only; group II received blood transfusion and then nitroprusside; group III received hydralazine. In group I, nitroprusside lowered right artrial pressure and systemic resistance; cardiac output was unchanged. In group II, transfusion raised right atrial pressure but not cardiac output. Then nitroprusside raised cardiac output significantly. Hydralazine decreased right atrial pressure less than nitroprusside but decreased vascular resistance and raised cardiac output. Both nitroprusside and hydralazine decreased systemic vascular resistance during tamponade, but only hydralazine raised cardiac output probably because of its lesser effect upon the capacitance vessels. Nitroprusside maintained cardiac output during tamponade despite lowered right atrial pressure but increased cardiac output only after transfusion.

Animals↗
PubMed1977

[Influence of modern inhalation anaesthetics on haemodynamics, myocardial contractility, left ventricular volumes and myocardial oxygen supply (author's transl)].

The cardiocirculatory responses to equianaesthetic concentrations (MAC 0.5 and MAC 1.0 plus 67% N2O) of halothane, methoxyflurane, enflurane and isoflurane were studied in a total of 35 closed-chest dogs during ventilation controlled to produce normocapnia. Each anaesthetic produced a dose-related decrease in mean arterial pressure and in values reflecting cardiac function. These included cardiac output, stroke volume, left ventricular max dp/dt and ejection fraction. Isoflurane seemed slightly less depressant to the heart than the other 3 anaesthetics. Total peripheral resistance remained nearly unaffected during halothane and methoxyflurane anaesthesia but decreased significantly with MAC 1.0 enflurane and isoflurane. There was no change in heart rate at low anaesthetic concentrations. The deeper levels of anaesthesia were associated with moderate increases in heart rate. In spite of the obvious depression of myocardial contractility there was a fall in pulmonary artery and left ventricular end-diastolic pressures and in left ventricular end-diastolic volumes with each of the agents. We take this as an expression of decreased ventricular filling resulted from pooling of blood in peripheral capacitive vessels. With the exception of isoflurane, each of the other three anaesthetics reduced coronary blood flow. Coronary vascular resistance was not substantially influenced by halothane and methoxyflurane, but decreased with MAC 1.0 enflurane and isoflurane. Myocardial oxygen availability was always found to be adequate. Isoflurane even produced a significant rise in coronary venous oxygen saturation indicating coronary vasodilation. Parallel with the depression in cardiac performance and blood pressure as two of the main predictors of energy demand, myocardial oxygen consumption was found to be significantly reduced by each of the anaesthetics. The ratio of the external work of the left ventricle to its oxygen consumption indicated that myocardial efficiency deterioated. The clinical implications are discussed.

Anesthetics↗
PubMed1983

Peripheral hemodynamics in patients with Fabry's disease.

Altered vasomotor activity has been reported as a clinically prominent feature of Fabry's disease (angiokeratoma corporis diffusum universale). While symptomatic cardiovascular involvement occurs eventually in most patients with this disorder, little is known concerning the effect of Fabry's disease on peripheral hemodynamics. Peripheral hemodynamics in the extremities and digits were studied in eight patients with Fabry's disease by means of segmental and venous occlusion pneumoplethysmography and thermal probes, and the results obtained were compared with those of 10 normal subjects. Forearm vascular resistance in Fabry's disease patients was significantly higher (p less than 0.01) than that in normal subjects. Forearm venous capacitance in Fabry's disease was significantly lower (p less than 0.01). Segmental pulse volume amplitudes showed no significant difference in any segments (upper arm, wrist, thigh, above and below knee, and the calf) between the two groups. Finger and toe blood flow, finger and toe pulse volume, and temperature in the resting state were all significantly less (p less than 0.01, p less than 0.05: p less than 0.01, p less than 0.01: p less than 0.05, p less than 0.05, respectively) than those in normal subjects. Finger and toe blood flow and pulse volume after vasodilation procedures were significantly less (p less than 0.05, p less than 0.01: p less than 0.05, p less than 0.01, respectively) than those in normal subjects despite equal elevation of digital temperature obtained after vasodilation in both groups. These findings indicate the presence of vasoconstrictive process in both resistance vessels and capacitances vessels in cutaneous and skeletal muscular beds. A limited response in the cutaneous circulation to vasodilation procedures also was seen. These data suggest the possibility that latent enhanced sympathoadrenal discharge as well as the accumulation of glycolipid in the autonomic nervous system and vessel walls plays an important role in the disturbed pathophysiology of this disorder.

Adolescent↗
PubMed1981

Hepatic capacitance responses to changes in flow and hepatic venous pressure in dogs.

The effect of changes in inflow and hepatic venous pressure (Phv) on the hepatic vascular bed was studied in denervated, pump-perfused canine livers. Hepatic arterial, portal venous, and hepatic venous pressures and flows were continuously monitored as was the hepatic venous hematocrit (Hct). The hepatic venous outflow, which averaged 1179 +/- 356 (SD) ml x min-1 x kg tissue-1 at control conditions, was controlled by a servosystem set to keep Phv at the desired level. Hepatic volume changes (delta V) were determined by integration of the difference between hepatic inflow (Fin) and outflow (Fhv). Over the range of Phv of 0-15 mmHg, the delta V-to-delta Phv ratio (apparent compliance C) was linear; C = 19.8 ml x mmHg-1 x kg tissue-1. These increases in Phv caused transient and plateau increases in Hct of 1.26 and 0.42%/mmHg, respectively. Varying inflow over the range of 0-156% of control by changing hepatic arterial and/or portal venous flow(s) resulted in delta V of 0.066 ml/kg per ml x min-1 x kg tissue-1 change in flow. We conclude that changes in Fin as well as changes in Phv cause changes in liver volume; and that a significant fraction of the volume shift accompanying changes in Phv is due to transsinusoidal plasma movement.

Animals↗
PubMed1985

Pressure and tone dependence of coronary diastolic input impedance and capacitance.

To quantify reactive elements of the coronary circulation, we have characterized in vivo diastolic coronary input impedance by introducing sinusoidal pressure oscillations of constant amplitude and varying frequency at constant mean pressure levels during prolonged diastoles in heart-blocked dogs anesthetized with pentobarbital. The behavior of coronary input impedance is similar to that observed in other peripheral vascular beds and is a function of both mean distending pressure and vasomotor tone. The behavior of impedance modulus and phase at each pressure level could be described by a lumped resistive-capacitive (RC) parallel model over a frequency range of 1-5 Hz. At higher frequencies the phase angle response could be characterized by adding a Voigt viscoelastic element to the original RC model. Calculated coronary capacitances for both models were similar in magnitude and varied inversely with mean coronary distending pressure. Values for the RC and RC viscoelastic model in the maximally dilated coronary bed were 14.1 and 21.6 X 10(-3) ml X mmHg X 100 g-1 at 30 mmHg and 2.65 and 2.70 X 10(-3) ml X mmHg-1 X 100 g-1 at 110 mmHg. With vasomotor tone intact, calculated coronary capacitance at each pressure level was reduced by a factor of two. These results indicate that an RC parallel model with pressure- and vasomotor tone-dependent capacitance adequately describes diastolic coronary input impedance at frequencies encountered during ordinary diastoles. The addition of a viscoelastic element provides adequate fits up to frequencies of 10 Hz.

Animals↗
PubMed2001

Evidence for stretch-induced resistance increase of proximal coronary microcirculation.

We investigated the influence of stretch on regional hemodynamic parameters of the septal circulation. We used a similar experimental setup and mathematical model, as described previously (14). Five ventricular septa were isolated from anesthetized dogs, sutured to a biaxial stretching apparatus, and perfused with an oxygenated perfluorochemical emulsion at maximal vasodilation. Under unloaded and biaxially stretched conditions, flow and septal thickness (to index vascular volume) were measured continuously. Pressure was varied sinusoidally at 30, 50, and 70 mmHg with amplitude of 7.5 mmHg over frequencies ranging between 0.015 and 7 Hz. Admittance (flow/pressure) and capacitance (thickness/pressure) transfer functions were calculated and interpreted in terms of a two-compartmental model with volume-dependent resistances. Parameter estimation showed that the proximal resistance and compliance were unaffected, whereas the resistance of the proximal part of the microcirculation, including the small arterioles, increased with stretch. The effect of stretch on the distal resistance and capacitance, however, could not be determined unequivocally.

Animals↗
PubMed1981

Peripheral and central vascular compliances in conscious normotensive and spontaneously hypertensive rats.

Changes of left atrial (LAP) and right atrial pressure (RAP) upon 10% and 20% blood volume expansion were studied in conscious spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKR) with intact nervous cardiovascular control. In a separate series the changes of central (CBV) and peripheral (PBV) blood volumes upon similar increases of total blood volume (TBV) were measured as well, throughout using male, adult SHR and WKR in both series. During volume expansion both LAP and RAP increased significantly more in SHR than in WKR, as did CBV, while PBV increased significantly less in SHR than in WKR. Total "effective' vascular compliance, defined as delta TBV/delta RAP, was significantly lower in SHR. From the two series of measurements central (CBV/LAP) and peripheral (PBV/RAP) vascular compliances could be separately deduced. Central vascular compliance was nearly 50% lower in SHR than in WKR. However, "unstressed' volume of the peripheral compartment appeared to be rather normal in SHR compared to WKR. It is therefore suggested that the decreased total vascular compliance seen in essential hypertension and in SHR is mainly due to a decreased distensibility of the systemic capacitance vessels.

Animals↗
PubMedDate not supplied

Parasympathetic influence on the nasal mucosa.

The effect of graded parasympathetic nerve stimulation on the exchange and capacitance vessels of the nasal mucosa, as well as the secretory response, is reported. Possible postganglionic mediators of the vascular and secretory effects are discussed.

Atropine↗
PubMed2001

Nitric oxide insufficiency, platelet activation, and arterial thrombosis.

Nitric oxide (NO) was originally discovered as a vasodilator product of the endothelium. Over the last 15 years, this vascular mediator has been shown to have important antiplatelet actions as well. By activating guanylyl cyclase, inhibiting phosphoinositide 3-kinase, impairing capacitative calcium influx, and inhibiting cyclooxygenase-1, endothelial NO limits platelet activation, adhesion, and aggregation. Platelets are also an important source of NO, and this platelet-derived NO pool limits recruitment of platelets to the platelet-rich thrombus. A deficiency of bioactive NO is associated with arterial thrombosis in animal models, individuals with endothelial dysfunction, and patients with a deficiency of the extracellular antioxidant enzyme glutathione peroxidase-3. This enzyme catalyzes the reduction of hydrogen and lipid peroxides, which limits the availability of these reactive oxygen species to react with and inactivate NO. The complex biochemical reactions that underlie the function and inactivation of NO in the vasculature represent an important set of targets for therapeutic intervention for the prevention and treatment of arterial thrombotic disorders.

Animals↗