Biomedical subjects

P E Chabrier

Publications and source records attributed to P E Chabrier.

At least 19 recordsLinked to original sources

PubMed1995

Inhibition of nitric oxide synthesis in the forearm arterial bed of patients with advanced cirrhosis.

Increased vascular production of nitric oxide (NO) may contribute to the peripheral vasodilation and hyperdynamic state complicating advanced liver cirrhosis. In this study, we examined the effect on forearm blood flow of local brachial artery infusion of noradrenaline (NA) and NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO-synthase, in 10 alcoholic ascitic cirrhotic patients (patients with decompensated alcohol-induced liver disease: DALD group) and 10 patients with well-compensated alcohol-induced liver disease (CALD group). Forearm blood flow was measured by venous occlusion plethysmography. As compared with the CALD group, the DALD group had higher cardiac index and forearm blood flow as well as lower systemic blood pressure and vascular resistance. Infusions of NA and L-NMMA produced similar reduction in resting blood flow in the CALD group. However, in the DALD group, NA was significantly less effective than L-NMMA. The forearm vasoconstrictor response to NA was also significantly reduced in the DALD group when compared with the CALD group. In the DALD group, NA decreased forearm blood flow by 21.0 +/- 6.2% and increased vascular resistance by 37.2 +/- 12.3%, whereas respective changes in the CALD group were 41.8 +/- 6.2% (P < .01) and 77.8 +/- 9.9% (P < .02). In contrast, L-NMMA induced greater forearm vasoconstriction in the DALD group than in the CALD group. In decompensated patients, L-NMMA decreased forearm blood flow by 50.4 +/- 2.7% and increased vascular resistance by 115.9 +/- 14.4%, whereas changes in compensated patients were 38.2 +/- 4.9% (P < .05) and 77.4 +/- 16.2% (NS), respectively. These results are consistent with the hypothesis that increased vascular synthesis of NO contributes to the high dynamic state of patients with advanced cirrhosis.

Arginine↗

PubMed1994

Endothelin-1 in patients with coronary heart disease undergoing cardiac catheterization.

OBJECTIVES: This study examined the possible association between endothelin and coronary atherosclerosis and evaluated the synthesis and release of endothelin in the presence of various stimuli that occur during cardiac catheterization. BACKGROUND: Circulating endothelin has been reported to be increased in diffuse atherosclerosis and acute myocardial infarction. However, the relation between coronary artery disease and endothelin release remains unclear. METHODS: We measured the plasma and urinary concentrations of endothelin immunoreactivity in 45 patients and 10 healthy control subjects. RESULTS: In group IA (n = 9), simultaneous blood sampling in the coronary sinus and femoral artery during coronary angioplasty of the left anterior descending coronary artery demonstrated no immediate changes in plasma immunoreactive endothelin-1 (ir-ET-1) levels. In 11 patients in group IB undergoing coronary angioplasty of a major artery, we did not detect changes in peripheral plasma concentrations of ir-ET-1 within 24 h, but urinary ir-ET-1 levels increased from 9.2 +/- 2.3 to 18.6 +/- 4.9 pg/mg of creatinine a few hours after coronary angioplasty (mean +/- SEM, p < 0.05). This increase in urinary endothelin excretion persisted 24 h later. Group II patients (n = 12) had coronary angiography without coronary angioplasty. Levels of both plasma and urinary ir-ET-1 did not change during the 24-h follow-up period. There was no relation between the severity of coronary atherosclerosis and the plasma or urinary concentrations of ir-ET-1. Systolic aortic pressure correlated with basal urinary excretion of endothelin (r = 0.54, p = 0.03, n = 15). In group III (n = 13), levels of ir-ET-1 in patients undergoing right heart catheterization without angiography did not differ from those in the control group. CONCLUSIONS: The presence or the severity, or both, of coronary atherosclerosis is not associated with a detectable increase in endothelin release. The diagnostic procedures of catheterization do not modify endothelin concentrations in plasma and urine. Vascular stretch or injury, or both, during coronary angioplasty increases urinary ir-ET-1 levels a few hours after the procedure. This increase persists for at least 24 h but is not detectable by brief sampling of peripheral or coronary sinus blood.

Angioplasty, Balloon, Coronary↗

PubMed1994

Changes in [3H]PAF binding and PAF concentrations in gerbil brain after bilateral common carotid artery occlusion: a quantitative autoradiographic study.

This study investigated the distribution of platelet activating factor (PAF) binding sites in the brain and their involvement in global ischemia in a model of bilateral common carotid occlusion in the gerbil. In sagittal sections of gerbil brain, labeling with [3H]PAF was mainly located in the cortex, hippocampus and cerebellum. The corpus striatum, the superior and inferior colliculi showed lower binding, while the thalamus was only weakly labeled. Scatchard analysis of the data obtained from displacement curves with unlabeled PAF revealed the presence of one or two populations of binding sites with different affinity constant values depending on the brain structures. When the gerbils were submitted to 10 min ischemia, similar autoradiography with [3H]PAF demonstrated a dramatic reduction of labeling in all brain structures, particularly in the hippocampus. Immunoreactive endogenous PAF concentrations in brain tissues showed a marked increase in ischemic animals: (8977.3 +/- 1113 pg/g wet weight) as compared to sham-operated control: (997.7 +/- 77 pg/g wet weight). Endogenous PAF levels returned to basal values following 30 min reperfusion. These results indicate that PAF may be involved in the early stages of brain ischemia in the gerbil and suggest that endogenous PAF produced during ischemia may contribute to the down-regulation of [3H]PAF binding sites in the brain.

Animals↗

PubMed1994

[Functions of the endothelium].

The venous endothelium, acting as an interface between the blood and the layer of smooth muscle cells, plays a major role in many essential functions of vessel physiology. The endothelium prevents and inhibits pathological activation of the coagulation system and plays an active role in the regulation of venous tone. Mediators include the prostacyclin which has vasodilating and antiagregating properties and nitric oxide (NO), a vasodilator and inhibitor of thrombosis, adhesion and cellular proliferation. To maintain endothelial integrity and tissue cohesion, endothelial cells express adhesion factors which regulate cell to cell and cell to extracellular matri interactions. Finally, the endothelium plays a role in vasotrophism by synthesizing, or activating growth factors which act directly on cell renewal of the endothelium itself and proliferation of adjacent tissues. Thus, the venous endothelium cannot be considered simply as a biologically inert barrier but rather as an active cell layer capable of intercell signalling and interactions constantly modified by the pathophysiological environment.

Blood Coagulation Factors↗

PubMed1994

Intravenously administered atrial natriuretic factor in patients with COPD. Effects on ventilation-perfusion relationships and pulmonary hemodynamics.

The potent pulmonary vasodilating property of atrial natriuretic factor (ANF) may alter gas exchange in patients with COPD. We examined the hemodynamic and gas exchange responses to intravenous infusion of ANF (0.01 and 0.03 ng/min/kg body weight) in eight stable patients with COPD studied during spontaneous breathing, using the inert gas elimination technique. When compared with baseline, ANF infusion was associated with a dose-dependent decrease in pulmonary artery pressure (from 27.3 +/- 2.5 to 23.9 +/- 1.8 and 20.2 +/- 1.7 mm Hg, respectively) and a dose-dependent increase in blood flow perfusing poorly ventilated and unventilated units (VA/Q < 0.1: from 5.80 +/- 2.05 to 7.25 +/- 2.5 and 12.0 +/- 5.4 percent of total blood flow, respectively; p = 0.02). However, PaO2 remained unchanged (70.2 +/- 3.6, 68.1 +/- 3.8 65.4 +/- 3.5 mm Hg, respectively) because of a significant increase in minute ventilation (VE) from 8.6 +/- 0.8 to 9.6 +/- 0.8 and 10.3 +/- 0.7 L/min (p < 0.002). Six additional COPD patients receiving intravenously administered ANF at the same dosages were studied during controlled mechanical ventilation using right heart catheterization. In these patients, pulmonary vasodilation was associated with a significant increase in venous admixture (from 12.7 +/- 2.4 to 14.4 +/- 2.9 and 17.5 +/- 3.5 percent of total blood flow, respectively; p < 0.02), and a dose-dependent reduction in arterial PO2 (from 117 +/- 17 to 110 +/- 15 and 96.4 +/- 8.8 mm Hg, respectively; p < 0.05). The present results show that ANF infusion is associated with alterations in the VA/Q relationship in patients with COPD. However, a decrease in arterial oxygenation may be prevented by an increase in VE.

Aged↗

PubMed1994

[Role of endothelial nitric oxide synthases in the contractile response to angiotensin II of the aorta in rats. Wistar Kyoto and hypertensive rats].

Dysfunctions of EDRF/L-arginine-NO pathway have been demonstrated in genetic and experimental hypertension. NO is produced through the conversion of L-arginine to L-citruline by NO synthases (NOS) which exist at least in two isoforms. The first termed constitutive (NOSc) and located in the endothelium of the vascular wall results in the basal and stimulated NO production. The second termed inducible (NOSi), which produces large amounts of NO, can be expressed in both smooth muscle and endothelial cells. The aim of the study was to examine and compare in isolated aortic rings of WKY and SHR rats, the activity of the two isoforms of endothelial NO synthases and their influence on the constrictor response induced by angiotensin II. On phenylephrine preconstricted endothelium intact aortic rings (10(-6) M, WKY = 1.2 +/- 0.04 g; SHR = 1.2 +/- 0.07 g; n = 7), carbachol (10(-5) M) induced a greater relaxation in WKY (84 +/- 2.5%) than in SHR (63 +/- 8.5%) rat. This suggests the presence of a low NOSc stimulated activity in the hypertensive strain. When the incubation period was limited to 30 min after equilibration period, L-arginine (3.10(-4) M) did not induce relaxation. When the incubation period was prolonged (180 min), L-arginine induced a relaxation (WKY = 75 +/- 8%; SHR = 58 +/- 10%; n = 7). This relaxation was not observed in a medium containing actinomycin D (10(-6) M) or after endothelium removal, indicating the induction of an endothelial NOSi in the two strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

PubMed1994

Endothelin receptor subtypes A and B are up-regulated in an experimental model of acute renal failure.

The two endothelin (ET) receptor subtypes (ETA and ETB) have been characterized in rat kidney from normal rats and rats with acute renal failure induced by hypertonic glycerol administration. In control rats, the total number of ET receptors in kidney cortex and medulla was 155 and 386 fmol/mg of protein, respectively. The ratio of ETA to ETB receptors was 54:46 in renal cortex and 35:65 in renal medulla. Treatment of rats with 10 ml/kg glycerol (50%, w/v) intramuscularly resulted in severe renal dysfunction; the serum urea concentration increased from 0.46 to 2.65 g/liter and the creatinine clearance decreased from 1.06 to 0.30 ml/min. Ligand binding studies showed that glycerol-induced acute renal failure was associated with a marked up-regulation of ETA and ETB receptor subtypes in both cortex and medulla. In glycerol-treated rats, the total ET receptor density in kidney cortex and medulla was increased to 294 and 1172 fmol/mg of protein, with ETA/ETB ratios of 52:48 and 31:69, respectively. The upregulatory effect of glycerol treatment was significantly more pronounced in renal medulla than renal cortex and affected ETB receptors preferentially, compared with ETA receptors. Subsequently, ETA and ETB receptor mRNA levels were markedly increased by glycerol administration in both kidney cortex and medulla, as assessed by polymerase chain reaction coupled to reverse transcription. These results suggest that up-regulation of renal ET receptors, particularly ETB receptors in kidney medulla, may account for or contribute to renal function impairment induced by glycerol, and they support a pathophysiological role for ET in acute renal failure.

Acute Kidney Injury↗

PubMed1993

Activation of the murine monocyte/macrophage cell line, J774A1 by poly(A).poly(U): I. Binding of poly(A).poly(U) and induction of oligo-2',5'-adenylate synthetase.

Binding and internalization of the synthetic double-stranded complex poly(A).poly(U) were studied on a murine monocyte/macrophage cell line J774A1. Poly(A).poly(U) increased in a dose-dependent fashion the oligo-2',5'-adenylate synthetase demonstrating that those cells were responsive to this agonist. Binding of [32P]poly(A).[32P]poly(U) to the cells reached an apparent kinetic equilibrium within 4 h and was saturable (apparent Kd = 9.99 +/- 0.09.10(-2) g/l and Bmax 13.3 +/- 5.3.10(-3) g/l per 10(6) cells) and temperature-dependent. The binding of poly(A).poly(U) was competitively inhibited by various polynucleotides but not by other structurally unrelated compounds. Analysis of cell-associated [32P]poly(A).[32P]poly(U) demonstrated a minimal degradation of this polyribonucleotide over a 4-h incubation period. Autoradiography of cells incubated with [3H]poly(A).[3H]poly(U) revealed that poly(A).poly(U) was internalized and migrated to cell nuclei. These results suggest that poly(A).poly(U) is internalized in J774A1 cells via an endocytotic process.

2',5'-Oligoadenylate Synthetase↗

PubMed1993

Nitric oxide synthase induction in glial cells: effect on neuronal survival.

In primary rat cortical glial cell cultures lipopolysaccharide (LPS) induced a dose- and time-dependent increase of intracellular cyclic GMP concentration associated with a release of nitrite. The LPS-induced cyclic GMP and nitrite increase was enhanced by interferon-gamma and was prevented by L-NG-nitroarginine, dexamethasone and cycloheximide. Thus indicates that LPS effect occurred via the production of nitric oxide (NO) and involved new protein synthesis suggesting the induction of NO synthase in these cells. Furthermore this induction was Ca(2+)-independent and was blocked by an inhibitor of the synthesis of tetrahydrobiopterin. The inducible NO synthase was also expressed by C6 glioma cells. In primary mixed cultures containing both neuronal and glial cells, the effects of LPS were less important than in primary glial cell cultures suggesting that glial cells rather than neurons expressed the inducible form of NO synthase. On the other hand no change on neuronal viability was observed after NO synthase induction by LPS in this culture type. This study indicates that glial cells are able to induce NO synthase without affecting neuronal survival.

Amino Acid Oxidoreductases↗

PubMed1993

The role of endothelin in the vessel wall.

Endothelins (ETs) are a family of vasoactive peptides occurring in three isoforms (ET-1, ET-2, ET-3) encoded by three distinct genes in the human genome. ETs arise from precursor peptides (big-ETs) that are cleaved and released by an endothelin-converting enzyme. ET-1 secretion, which can be stimulated by various agents, is preferentially directed towards the abluminal site of endothelial cells, suggesting a local paracrine action of the peptide. ETs exert their actions through the activation of at least two receptor subtypes: ET-A receptors, which mediate the proliferative and vasoconstrictive effects, and ET-B receptors, which mediate vasorelaxation. Although, the potential roles of ETs are mostly hypothetical, considering their potent cardiovascular effects, it has been suggested that maintenance of a basal vascular tone and regulation of vascular growth and haemostasis may well represent the biological functions of this family of peptides. The recent discovery of specific receptor antagonists will provide a means to assess their physiological and pathophysiological roles.

Amino Acid Sequence↗

PubMed1993

Vascular remodeling and antihypertensive therapy: the example of cicletanine.

Hypertension causes major structural vascular modifications including increase of wall:lumen ratio, vessel wall hypertrophy, and rarefaction of arterioles and small arteries. These structural alterations are accompanied with vascular dysfunctions. The stimuli responsible for this vascular remodeling are numerous and comprise physical, humoral, and locally synthetized factors. Among them, vasoactive substances such as vasoconstrictors (e.g., angiotensin II and endothelin) or vasodilating substances (e.g., prostacyclin and nitric oxide) may play a role as important as those of growth factors. The vascular protection afforded by antihypertensive drugs depends on their mode and their site of action and probably on their direct interference with the local hemodynamic and growth-affecting factors. This is well illustrated by cicletanine, a new antihypertensive agent that provides a good example of protection of the vasculature. This also emphasizes that vascular remodeling is important in hypertension and must be considered as an essential property of any new antihypertensive drug.

Animals↗

PubMed1993

Upregulation of renal endothelin receptors in glycerol-induced acute renal failure in the rat.

Acute renal failure was induced in rat with a hypertonic glycerol solution and endothelin-1 (ET-1) binding was measured in kidney membrane preparations. In control animals, [125I]-ET-1 bound to specific recognition sites in kidney cortex (Bmax = 134 +/- 11 fmol/mg protein) and medulla (Bmax = 300 +/- 9 fmol/mg protein) with an apparent dissociation constant (Kd) of 0.16 +/- 0.06 nM and 0.39 +/- 0.07 nM for cortex and medulla, respectively. A single i.m. dose of 10 ml/kg glycerol (50% w/v) resulted in alterations of renal function that were maximal 48 h after glycerol administration. After this 48-h period, serum urea was increased from 0.20 +/- 0.01 g/L to 1.16 +/- 0.20 g/L (p < 0.001) and creatinine clearance was reduced from 1.04 +/- 0.15 ml/min to 0.23 +/- 0.06 ml/min (p < 0.001). Renal ET-1 receptor density was significantly increased in glycerol-treated rats to 255 +/- 14 fmol/mg protein in renal cortex (p < 0.01), and 576 +/- 55 fmol/mg protein in renal medulla (p < 0.01), with no significant modification of the Kd values. These results suggest that upregulation of ET-1 receptors is involved in renal hemodynamic impairment induced by glycerol.

Acute Kidney Injury↗

PubMed1993

Elevated tissue endothelin content during focal cerebral ischemia in the rat.

To study the involvement of endogenous endothelin (ET) in the development of cerebral ischemia, we measured by radioimmunoassay brain tissue content of immunoreactive (ir)-ET-1 in a model of focal cerebral ischemia in the rat. Permanent occlusion of the middle cerebral artery (OMCA) was accompanied after 24 h by a progressive but marked elevation of ir-ET-1 in the ipsilateral compared with the contralateral hemisphere (119% after 24 h; 184% after 48 h and 459% after 72 h). The pial vessels and the arteries of the circle of Willis did not respond with ir-ET-1 production. The increase in ir-ET-1 content in tissues was first observed in the caudate nucleus (after 24 h) and later in the cortex (after 48 h), which was more variably injured. Transient ischemia followed by recirculation led to a slight increase of ir-ET-1, which also appeared after 24 h of recirculation. This study demonstrates that during permanent OMCA, the tissue content of ir-ET-1 markedly and progressively increases, whereas less severe ischemia (transient) is accompanied by a modest elevation of ir-ET-1 levels. These results suggest that endogenous ir-ET-1 production is involved in the development and the severity of ischemic injury.

Animals↗

PubMed1993

Dilator effect of endothelins in pulmonary circulation: changes associated with chronic hypoxia.

To investigate dilator effects of endothelins (ETs) on the pulmonary circulation and possible changes induced by chronic hypoxia, we examined vascular responses to ET-1 and ET-3 as well as ET binding to receptor subtypes ETA and ETB in the lungs from rats exposed to either room air (controls), hypoxia (10% O2) for 3 wk (3 WH), or 3 WH followed by recovery to room air (3 WH+R). In controls, both ETA and ETB receptor binding was present in smooth muscle of airways and vessels. Infusion of ET-1 or ET-3 (3-100 pM) to isolated perfused lungs preconstricted by U-46619 produced dose-dependent vasodilation with a greater potency of ET-3 (P < 0.01). The vasodilator responses to ET-1 and ET-3 were potentiated by the cyclooxygenase blocker meclofenamate (3 x 10(-6) M) or by the thromboxane synthetase inhibitor R-68070. In meclofenamate-treated lungs, the vasodilator responses to ET-1 and ET-3 remained unaffected by the inhibitor of nitric oxide synthesis, NG-monomethyl-L-arginine (5 x 10(-4) M) or by the guanylate cyclase inhibitor, methylene blue (10(-4) M). Conversely, the K+ channel blockers glibenclamide (10(-4) M) and tetraethylammonium (10(-4) M) attenuated the vasodilator responses to both ET-1 and ET-3. The selective ETA receptor antagonist BQ-123 did not alter ET-induced vasodilation, whereas it attenuated ET-induced vasoconstriction. Vasodilation to both ET-1 and ET-3 was abolished in lungs from 3 WH rats (P < 0.01) but was fully restored in lungs from 3 WH+R rats. Pulmonary vasodilation induced by the K+ channel opener pinacidil, which was suppressed by glibenclamide, did not differ between controls and 3 WH rat lungs. We found no change in ETA and ETB receptor binding from pulmonary vessels in H rat lungs compared with controls. In conclusion, endothelin-induced pulmonary vasodilation which may involve activation of K+ channels is abolished during chronic hypoxia. This abolition does not appear to be related to alterations in ET-receptor subtypes or to unresponsiveness of K+ channels in the pulmonary circulation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1993

Role of atrial natriuretic factor in impaired sodium excretion of normocapnic and hypercapnic patients with chronic obstructive lung disease.

To investigate the mechanisms of sodium retention in patients with chronic obstructive lung disease (COLD), we examined the renal and hormonal responses to volume expansion with isotonic saline and to infusion of atrial natriuretic factor (ANF) in 10 hypercapnic (PaCO2 52 +/- 2 mm Hg) and 12 normocapnic patients (PaCO2 39 +/- 1 mm Hg). Sodium excreted within 4 h of loading (expressed as % sodium load) was 23.5 +/- 2.5% (p < 0.05) in normocapnic and 8.5 +/- 1.5% (p < 0.001) in hypercapnic patients, compared with 32.5 +/- 3.0% in 11 age-matched control subjects. Sodium excretion and renal blood flow correlated negatively with arterial PCO2 and positively with FEV1. Basal plasma ANF concentrations were 72 +/- 5 pg/ml in controls, 100 +/- 14 pg/ml in normocapnic patients, and 230 +/- 52 pg/ml in hypercapnic patients (p < 0.001). Plasma renin activity and aldosterone did not differ between groups. In response to volume expansion, plasma ANF increased in both normocapnic and controls (with a greater increase in normocapnic patients) but remained unchanged in hypercapnic patients. Exogenous ANF increased glomerular filtration rate, renal plasma flow, natriuresis, and diuresis in both groups of patients. Patients with COLD have depressed renal function that appears unrelated to activation of the renin-angiotensin-aldosterone system. An increased secretory response of ANF to volume expansion may help to maintain volume homeostasis in normocapnic patients, while a blunted secretory response of ANF may contribute to sodium retention in hypercapnic patients.

Aged↗

PubMed1992

The vasoconstrictor action of big endothelin-1 is phosphoramidon-sensitive in rabbit saphenous artery, but not in saphenous vein.

The effects of big endothelin-1 and endothelin-1 on vascular reactivity were compared in isolated rabbit saphenous artery and vein. The contractile potency of endothelin-1 was three times higher in the vein than in the artery. In contrast, big endothelin-1 was two times more effective in the artery. Phosphoramidon (100 microM), a metalloproteinase inhibitor, antagonised the contractile action of big endothelin-1 in the artery but not in the vein. These data suggest that the biosynthetic pathway leading to the formation of endothelin differs in arterial and venous vessels.

Animals↗

PubMed1992

Effects of infusion of L-arginine into the left anterior descending coronary artery on acetylcholine-induced vasoconstriction of human atheromatous coronary arteries.

Hypercholesterolemia and atherosclerosis are conditions associated with impaired endothelium-dependent relaxation. In hypercholesterolemic animals, intravenous administration of L-arginine, the precursor of nitric oxide, normalizes endothelium-dependent vasodilator activity. In the present study, we questioned whether intracoronary administration of L-arginine in patients with coronary artery disease could improve coronary vascular reactivity to acetylcholine. Thirteen hypercholesterolemic patients with diffuse coronary atherosclerosis but nonstenotic lesions of the left anterior descending (LAD) coronary artery were investigated. Quantitative coronary angiography and subselective intracoronary Doppler flow velocity measurements were performed to determine LAD diameters and coronary blood flow. Intracoronary infusion of acetylcholine was performed during 3 consecutive 3-minute periods at incremental rates adjusted to achieve estimated final concentrations of 5 x 10(-7), 10(-6) and 5 x 10(-6) M. After evaluation of the response to acetylcholine, L-arginine was infused into the LAD at the rate of 25 mg/min (10(-3) M) and the same stepwise 3-minute infusions of acetylcholine were repeated during infusion of L-arginine. Infusion of acetylcholine induced a dose-dependent reduction of distal epicardial LAD diameter reaching -48.5 +/- 17% at 5 x 10(-6) M (p < 0.01 vs control values). L-arginine alone had no effect on the distal LAD diameter but attenuated acetylcholine-induced vasoconstriction to -21 +/- 9% at 5 x 10(-6) M acetylcholine (p < 0.01). Coronary blood flow showed a biphasic response to acetylcholine, increasing by 41 +/- 12% at 5 x 10(-7) M (p < 0.01) and decreasing by 21 +/- 13% at 5 x 10(-6) M (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1992

Induction of nitric oxide synthase by lipoteichoic acid from Staphylococcus aureus in vascular smooth muscle cells.

Inducible vascular nitric oxide synthase accounts for the contractile impairment observed in endotoxemia. We provide evidence that lipoteichoic acid (LTA) from Staphylococcus aureus, a micro-organism without endotoxin, also induces nitric oxide synthase. Our study demonstrates that on endothelium-free rings of rat aorta. LTA-like lipopolysaccharide induces a loss of contractility restored by Methylene blue and NG-nitro-L-arginine-methyl ester (LNAME). Moreover in cultured vascular smooth muscle cells, LTA produces a dose-dependent increase in intracellular cyclic GMP which is antagonized by LNAME and prevented by dexamethasone.

Amino Acid Oxidoreductases↗