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N P Curzen

Publications and source records attributed to N P Curzen.

At least 19 recordsLinked to original sources
PubMed2006

The limitations of coronary angiography: identification of a critical coronary stenosis using intravascular ultrasound.

Coronary angiography is considered the gold standard method of imaging coronary stenoses. Quantitative coronary angiography (QCA) has helped to provide information about the degree of stenosis which is used as a surrogate to indicate impaired flow in a coronary bed. QCA however can underestimate disease severity. In this case intravascular ultrasound identifies a critical coronary stenosis not seen on angiography.

Adult↗
PubMed2006

Thromboelastography: potential bedside tool to assess the effects of antiplatelet therapy?

Modified thrombelastography (TEG) is a simple point of care test that provides an overall assessment of ex vivo clot formation and currently has limited clinical application. We evaluated the ability of TEG to assess the effects of antiplatelet therapy on clot formation using a novel assessment parameter (the area under curve). Forty healthy volunteers were divided into four groups of 10. Group A took aspirin 75 mg once daily for 7 days followed by aspirin 75 mg and clopidogrel 75 mg once daily in combination for 7 more days. Blood samples were taken for analysis at day 0 and days 7 and 14. Group B took a single 300 mg dose of aspirin. Group C took 600 mg of clopidogrel only. Group D took 300 mg of aspirin and 600 mg of clopidogrel at the same time. For groups B, C and D blood was taken prior to drug administration and at 2, 6 and 24 h afterwards. Each sample was tested by TEG in four channels following activation using (1) kaolin, (2) activator F (Act F), a direct activator of fibrin, (3) Act F + arachidonic acid (AA) and (4) Act F + adenosine diphosphate (ADP). Parameters measured included the maximum amplitude (MA) of the clot and the area under the TEG-generated curve at 1 h. Significant, time-dependent reductions in MA and area were seen in the AA-activated samples following administration of aspirin in all groups as compared to baseline. By contrast, there were no significant differences in MA or area in the AA-activated samples with clopidogrel alone. Significant reductions were also seen in MA and area in ADP-activated samples from volunteers treated with clopidogrel as compared to baseline. Three out of 10 subjects receiving 600 mg clopidogrel had a reduction in their responses of 30% or less, thus identifying them as relatively resistant to the drug. This study identifies a rapid, reliable method for assessing the time-dependent effects of antiplatelet therapy on clotting using a novel parameter of area of the TEG trace, which could have an important clinical application as a point of care test of efficacy, particularly in the context of acute coronary syndromes and percutaneous coronary intervention.

Adult↗
PubMed2006

Thrombelastography: current clinical applications and its potential role in interventional cardiology.

Thrombelastography is a bedside blood test used to assess patients' haemostatic status. It has a well-established role in hepatobiliary and cardiac surgery and is also used in obstetrics and trauma medicine to assess coagulation and identify the causes of post-operative bleeding. It is not routinely used in the diagnosis or treatment of thrombosis although recently it has been shown to predict thrombotic events post-operatively and after percutaneous intervention (PCI). In cardiovascular medicine the importance of the platelet in the pathophysiology of vascular events is increasingly apparent. As a result antiplatelet therapy is a cornerstone of the treatment for coronary disease, particularly in the setting of acute coronary syndromes. The increasing utilization of stents, particularly drug-eluting devices, in PCI has also necessitated widespread use of antiplatelet agents to minimize the risk of stent thrombosis. A quick, accurate and reliable test to measure the effect of platelet inhibition by antiplatelet agents on clotting in an individual patient would be of profound clinical value. The results from such a test could provide prognostic information, allow treatment with antiplatelet agents to be tailored to the individual and identify resistance to one or more of these agents. Optimization and tailoring of anti-platelet therapy in patients with cardiovascular disease, particularly those undergoing PCI, using such a test may reduce morbidity and mortality from thrombotic and haemorrhagic complications. Current methods of assessing platelet activity measure platelet count and function in isolation. Optical aggregation is the most widely used method for assessing platelet function but it is relatively time consuming, measures platelet function in isolation rather than in the context of clot formation and is not a bedside test. By contrast the modified thrombelastograph platelet mapping kit marketed by Haemoscope can be used to assess the effects of antiplatelet agents on ex vivo blood clotting, thus giving a measurement more relevant to in vivo responses. This represents a potentially powerful tool to assess response of individual patients to antiplatelet therapy, particularly in the context of PCI.

Anticoagulants↗
PubMed2005

Patients undergoing coronary revascularisation: a missed opportunity for secondary prevention?

BACKGROUND: This study tested the hypothesis that the opportunity to start secondary prevention therapy before discharge after coronary revascularisation is being missed. The study assessed current prescribing practice and identified discrepancies in prescribing for patients managed by surgeons (especially) and cardiologists. METHODS: 200 consecutive patients from the Manchester Heart Centre percutaneous coronary intervention (PCI) and coronary artery bypass (CABG) registries were identified (100 from each registry) and the notes analysed. All had undergone coronary revascularisation from February 2002 to March 2002. Data were analysed using SPSS for Windows, version 10.1. RESULTS: After exclusion of two patients with contraindications, 100% (98 of 98) of PCI patients and 92% (90 of 98) CABG patients were prescribed aspirin at discharge. Eight two per cent of eligible PCI patients and 70% of eligible CABG patients were prescribed beta blockers at discharge. Ninety six per cent (96 of 100) of PCI patients and 73% (73 of 100) of CABG patients were prescribed statins of any dose at discharge, (p<0.001). Sixty five per cent of PCI but only 26% of CABG patients were discharged prescribed ACE inhibitors (eligible patients based on HOPE, heart outcomes prevention evaluation trial), (p<0.001). CONCLUSIONS: Secondary prevention prescription after coronary revascularisation remains suboptimal in all but aspirin use. Patients in the PCI group were statistically more likely to be discharged prescribed a statin or an ACE inhibitor, or both, than patients after CABG. Both interventional cardiologists and (especially) cardiac surgeons must improve their use of secondary prevention therapy.

Adrenergic beta-Antagonists↗
PubMed2004

A reverse perfusion pattern during Technetium-99m stress myocardial perfusion imaging does not predict flow limiting coronary artery disease.

BACKGROUND: A reverse redistribution pattern during myocardial perfusion imaging is most widely described using thallium (Tl-201), when stress images exhibit greater perfusion than rest. Technetium (Tc-99 m) radiopharmaceuticals may also yield a reverse perfusion (RP) pattern, but its significance is uncertain. This study tested the hypothesis that RP correlates with the presence and location of flow limiting coronary stenosis(es). METHOD: We reviewed 842 consecutive Tc-99 m tetrofosmin SPECT stress studies performed at a cardiothoracic centre over a 15 month period. 69 (8.2%) demonstrated RP. Thirty-three patients (age 32-79 mean 56, 17 female) had undergone cardiac catheterisation within 12 months of the scan. Correlation was sought between the presence and location of angiographic stenoses and RP pattern. RESULTS: 10/33 (30.3%) had significant (>60%) coronary stenosis(es); 5 single-vessel, 2 two-vessel and 3 three-vessel disease (3VD). Stenosis location correlated poorly with the RP territory (LAD/Anterior 5/17, RCA/Inferior 1/10, Cx/lateral 0/4 (p = 0.57)). Of the 6 patients with a lesion in the RP territory, 3 had 3VD; 2 of these had a simultaneous reversible defect. All 5 patients with previous myocardial infarction had a simultaneous fixed defect. However only 3/12 with co-existent reversible defects had significant disease. CONCLUSION: The reverse perfusion pattern is a poor predictor of flow limiting coronary disease, and does not correlate with stenosis location in those with significant lesions. Such patients should not undergo invasive investigation purely on the basis of this result.

Adult↗
PubMed2003

Off-pump coronary artery bypass graft surgery: the incidence of postoperative atrial fibrillation.

Atrial fibrillation (AF) occurs in one quarter to one third of patients after coronary artery bypass graft surgery (CABG). Conventional CABG uses cardiopulmonary bypass, a process that is itself associated with a systemic vascular inflammatory response that contributes to postoperative morbidity. The avoidance of cardiopulmonary bypass is associated with a significant reduction in the inflammatory response and in the release of markers of myocardial necrosis when compared with conventional CABG. There is speculation that off-pump CABG may reduce the incidence of postoperative AF through reduced trauma, ischaemia, and inflammation. Current data, however, do not emphatically answer the question of whether the incidence of post-CABG AF is reduced by off-pump surgery. The evidence from both observational and randomised studies is conflicting and many studies have weaknesses in design, conduct, or interpretation. It remains an attractive hypothesis that postoperative AF is reduced by off-pump CABG but more robust data are required.

Atrial Fibrillation↗
PubMed2000

Atrial fibrillation after coronary artery bypass surgery: a model for preoperative risk stratification.

BACKGROUND: Atrial fibrillation (AF) occurs in 20% to 40% of patients after CABG. Identification of patients vulnerable for arrhythmia will allow targeting of those most likely to benefit from prophylactic therapy. The aim of the present study was to evaluate accuracy of a prospectively defined signal-averaged P-wave duration (SAPD) cutoff and additional preoperative characteristics for the prediction of AF after CABG. METHODS AND RESULTS: Patients undergoing elective isolated CABG were recruited to the present prospective study. SAPD was recorded in all patients. Filtered signals from 3 orthogonal leads were combined in a vector analysis, and total SAPD was measured preoperatively. Postoperative in-hospital AF occurred in 92 (28.2%) of 326 patients. Patients who developed AF were older (65.9 versus 61.7 years of age; P<0.0005) and had longer SAPD (158 versus 145 ms; P<0.0005) than non-AF patients. Incidence of AF increased in patients > or =75 years of age and increased progressively throughout the range of SAPD. Stepwise logistic regression analysis of preoperative variables identified that SAPD >155 ms (odds ratio, 5.37; 95% CI, 3.10 to 9.30; P<0.0005), advanced age (odds ratio, 1. 53; 95% CI, 1.26 to 1.86 per 5-year increase in age; P<0.0005), and male sex (odds ratio, 2.88; 95% CI, 1.30 to 6.40; P<0.01) independently predicted AF. Prospectively defined SAPD >155 ms predicted AF with positive and negative predictive accuracy of 49% and 84%, respectively. CONCLUSIONS: A combination of prolonged SAPD, advanced age, and male sex identifies patients at high risk for development of AF after CABG.

Adrenergic beta-Antagonists↗
PubMed1999

Stent implantation reduces restenosis in patients with suboptimal results following coronary angioplasty.

BACKGROUND: Primary intracoronary stenting reduces the rate of restenosis when compared with balloon angioplasty (PTCA) in selected patients. The strategy of PTCA followed by provisional stent placement for suboptimal PTCA results may be preferable to universal stenting but has not yet been tested in a randomized trial. METHODS: An attempt was made to obtain an optimal result with PTCA alone in 143 patients. Stenting was required in 50 patients (35%) for significant coronary dissection or PTCA failure. In the remaining 93 patients, the angiographic result was assessed immediately using on-line quantitative coronary angiography and classified as either optimal (<15% residual stenosis) or suboptimal (>/=15% residual stenosis). Sixteen patients (11%) had an optimal result from PTCA. The remaining 77 (54%) patients had a suboptimal result and were immediately randomized either to no further treatment or to the placement of a stent. The primary end-point was the rate of restenosis (>50% stenosis), assessed by quantitative coronary angiography, at 6 months. RESULTS: Angiographic follow-up was completed in 132 patients. Restenosis occurred in 53 (36,69)% of patients with a suboptimal result randomized to PTCA alone compared with 24 (12,41)% of patients randomized to stent (P=0.023). There was no significant difference in minimal luminal diameter at follow-up between the randomized groups. The rate of restenosis was 14 (2,43)% in patients with an optimal PTCA result and 14 (5,28)% in those that required stenting. CONCLUSIONS: Optimal angiographic results following conventional PTCA are rare and the restenosis rate following suboptimal results is high. The strategy of stenting suboptimal results is associated with a significant reduction in the rate of stenosis.

Angioplasty, Balloon, Coronary↗
PubMed1998

Can C reactive protein or troponins T and I predict outcome in patients with intractable unstable angina?

OBJECTIVE: To determine whether a single blood test for the measurement of C reactive protein, or troponin I or T concentrations could be used to stratify patients with intractable unstable angina awaiting transfer for coronary angiography by correlating these values with coronary anatomy and transient myocardial ischaemia. DESIGN: Prospective study. SETTING: Tertiary cardiac unit. PATIENTS: All patients admitted to their local hospital with ischaemic chest pain, uncontrolled by medical treatment, in whom acute myocardial infarction had been excluded by serial measurement of creatine kinase and lack of Q waves on ECG. INTERVENTION: Coronary angiography and ST segment monitoring for 24 hours. MAIN OUTCOME MEASURES: Concentrations of C reactive protein, troponins T and I, coronary anatomy, presence of transient myocardial ischaemia. RESULTS: Median C reactive protein, troponin I, and troponin T concentrations were 17.1 mg/dl (4.8 to 203.9), 0.05 microgram/l (0 to 7.8), and 0.0 microgram/l (0 to 2.51), respectively. Seven patients (10%) had normal coronaries and 14, 20, and 31 had one, two, or three vessel coronary disease, respectively. Nineteen (26%) had transient myocardial ischaemia, 33 (46%) had complex lesion morphology, and six (8%) had intracoronary thrombus. Of the three markers, troponin T alone was higher in patients with multivessel disease (p < 0.05) and in those with transient myocardial ischaemia (p < 0.05), but there was no significant relation between C reactive protein, troponin T or I and lesion morphology or thrombus. CONCLUSIONS: In patients transferred to a tertiary centre with intractable chest pain, C reactive protein and troponin I are not predictive of transient myocardial ischaemia or lesion morphology, both of which are surrogate markers of outcome. Troponin T is, however, raised in patients with multivessel disease or transient myocardial ischaemia. These serum protein assays cannot be used to stratify the risk of patients with unstable angina who are awaiting transfer to the tertiary centre.

Adult↗
PubMed1997

Evidence for a dilator function of 8-iso prostaglandin F2 alpha in rat pulmonary artery.

1. 8-Iso prostaglandin F2 alpha (8-iso PGF2 alpha) is one of a series of prostanoids formed independently of the cyclo-oxygenase pathway. It has been shown to be upregulated in many conditions of oxidant stress where its formation is induced by free radical-catalysed actions on arachidonic acid. As 8-iso PGF2 alpha is formed in vivo in diseases in which oxidant stress is high such as septic shock, we have assessed the relative potency and efficacy of this compound in pulmonary arteries from control and lipopolysaccharide (LPS)-treated rats. 2. Several studies have characterized the contractile actions of 8-iso PGF2 alpha on various smooth muscle preparations, but its potential dilator actions have not been addressed. Thus these studies examined both the contractile and dilator actions of 8-iso PGF2 alpha in rat pulmonary artery rings. The thromboxane mimetic U46619, PGE2 sodium nitroprusside (SNP) and acetyl choline (ACh) were used for comparison. Each prostanoid had to be dissolved in ethanol to a maximum concentration of 1 x 10-2 M. At high concentrations, ethanol directly contracted pulmonary vessels. We were therefore limited by the actions of the vehicle such that we were unable to add prostanoids at concentrations higher than 1 x 10-4 M. In some cases this meant that maximum responses were not achieved and in these cases the Emax and pD2 values are apparent estimates. 3. The following rank order of potency was obtained from contractile studies; U46619 > 8-iso PGF2 alpha > PGE2, each prostanoid producing concentration-dependent contractions (10(-10)-3 x 10(-4) M, 10(-9)-10(-4) M, 10(-8)-10(-4) M, respectively). As has been shown previously for other smooth muscle preparations, the thromboxane receptor (TP) antagonist ICI 192605, (1 x 10(-6), 1 x 10(-5) and 1 x 10(-4) M), inhibited the contractions of 8-iso PGF2 alpha in a concentration-dependent fashion. 4. The nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 1 x 10(-4) M), enhanced the contractile function of both 8-iso PGF2 alpha and PGE2, but had no effect on that caused by U46619. Similarly, L-NAME inhibited the dilator function of all agents tested except the exogenous nitric oxide (NO) donor SNP indicating that PGE2 and 8-iso PGF2 alpha like ACh, act through the release of NO. The specificity of the effects of L-NAME were confirmed in studies with the inactive enantiomer D-NAME (1 x 10(-4) M), which did not affect the contractile or the dilator actions of 8-iso PGF2 alpha. Furthermore, ICI 192605 enhanced the dilator actions of 8-iso PGF2 alpha, suggesting that the dilator component of 8-iso PGF2 alpha was achieved via activation of a non-TP receptor. 5. Isoprostanes may modulate vascular tone by a direct action on TP receptors to cause contraction and via a distinct receptor leading to the release of NO to cause dilation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Do ACE inhibitors modulate atherosclerosis?

The ACE/angiotensin II/bradykinin system is inextricably linked to some of the processes that contribute to the generation of atherosclerosis at genetic, molecular, biochemical and pharmacological levels. There is a large body of laboratory-derived experimental data that suggests that inhibition of ACE activity has antiproliferative, anti-inflammatory and vasodilatory effects that can modulate this atherosclerotic process from the earliest form of endothelial dysfunction, to delay of lesion formation in primary atherosclerosis or in myointimal proliferation after PTCA. The clinical evidence for these potential benefits is so far sparse. There are several possible explanations for these discrepancies. Firstly, the role of the ACE/bradykinin/angiotensin II system in the local vascular response to either the primary process of atherosclerosis, or to the injury induced by balloon angioplasty is likely to vary between species and models. Secondly, there is a tendency to ensure the presence of ACE inhibitor in high concentration before or during the vascular insult in animal models, whereas this has not been the case in the clinical studies of post-PTCA restenosis. Whilst the animal studies therefore offer potentially valuable insights into the mechanics of local vascular response, the ability of ACE inhibitors to interfere with such mechanisms now needs to be tested in clinical trials that are each aimed at precisely answering specific questions. The experimental data so far lend considerable support to the fact that drugs acting solely by interference with the angiotensin II-receptor complex are at a theoretical disadvantage, when compared with ACE inhibitors, since the former would be expected to have little effect on bradykinin-mediated activities. To the established benefits of ACE inhibitors in left ventricular dysfunction, and the interesting possibility that there may be an anti-ischaemic action in these circumstances, we may add the promise of the TREND study. In the coming years, there is an urgent requirement for intensive investigation into the ability of ACE inhibitors to modulate the various stages of the atherosclerotic spectrum. For now though, the jury remains out.

Angioplasty, Balloon, Coronary↗
PubMed1997

Endothelin-1 in rat endotoxemia: mRNA expression and vasoreactivity in pulmonary and systemic circulations.

Endothelin-1 (ET-1) is a vasoconstrictor and proinflammatory peptide, but its role in the vascular response to sepsis is unknown. After intraperitoneal injection of male Wistar rats (300 g) with 20 mg/kg of Salmonella enteritidis lipopolysaccharide (LPS), the expression of ET-1 mRNA was significantly increased in pulmonary artery and aorta within 1 h and arterial ET-1 concentration was elevated. Despite this increase in ET-1 production, there was no difference in baseline systemic or pulmonary arterial pressures between control and endotoxin-treated rats, and, furthermore, combined ETA/ETB receptor antagonism using bosentan produced reductions in systemic and pulmonary arterial pressures that were not greater than the modest fall seen in controls. However, bosentan completely antagonized the hemodynamic effects of exogenous ET-1 in controls but only weakly antagonized its effects in LPS animals. After LPS the initial (ETB-mediated) systemic hypotensive responses to ET-1 were attenuated, but the subsequent systemic pressor responses were not. By contrast, the increases in pulmonary arterial pressure in response to ET-1 and the ETB receptor agonist sarafotoxin S6c were significantly reduced in LPS animals. Vascular ET-1 mRNA expression and arterial ET-1 concentration are elevated after LPS treatment in rats, but the functional activity of ET-1 cannot be exposed by combined ETA/ETB receptor antagonism, possibly because of an alteration in the functional status of ET receptors.

Animals↗
PubMed1997

In vivo treatment with endotoxin increases rat pulmonary vascular contractility despite NOS induction.

Pulmonary hypertension is a feature of clinical and experimental acute lung injury. Nitric oxide (NO) synthesis is increased in hyporesponsive systemic and pulmonary conductance arteries after endotoxin (LPS) injection in the rat. We examined the effects of NO synthase (NOS) induction by LPS on vascular reactivity of the isolated perfused rat lung (IPL) using the selective inducible (iNOS) inhibitor aminoguanidine (AG). Baseline pulmonary artery pressures (Ppa) were higher in the LPS compared with the sham-treated rats and were further increased only in the LPS-treated group by AG. Increased NOS activity in whole lung and the vasopressor effect of AG suggested that iNOS was active in pulmonary resistance vessels after LPS treatment. Vasoconstriction to hypoxia, angiotensin II (AII), and prostaglandin F2 alpha (PGF2 alpha) was enhanced or unchanged in LPS-treated rats despite NOS induction. Hence, iNOS activity counterbalances increased pulmonary vascular contractility in this model.

Angiotensin II↗
PubMed1996

Tissue expression of endothelin-1 mRNA in endotoxaemia.

Circulating endothelin-1 concentrations are elevated in animal models of sepsis. The major actions of endothelin-1 appear to be as a local autocrine and paracrine factor, rather than as a circulating hormone, and plasma concentrations may not reflect local tissue concentrations. We therefore measured tissue expression of mRNA encoding pre-pro-endothelin-1 by RNase protection assays, as an indicator of local production of ET-1 in an in vivo rat model of endotoxaemia. The effects of dexamethasone pre-treatment were also examined. There was a tissue-specific increase in pre-pro-endothelin-1 mRNA in endotoxaemia, apparent at 6h after endotoxin challenge in heart and lung. No significant changes in expression were seen in kidney or skeletal muscle. Dexamethasone pre-treatment significantly attenuated the rise in pre-pro-endothelin-1 mRNA in heart at 6h. Therefore, we have demonstrated tissue-specific differences in the effect of endotoxin upon pre-pro-endothelin-1 mRNA expression and in sensitivity to dexamethasone. This could account for some of the inter-tissue differences seen in local vascular response to endotoxin.

Animals↗
PubMed1996

Endothelin-1-induced contraction of pulmonary arteries from endotoxemic rats is attenuated by the endothelin-A receptor antagonist, BQ123.

OBJECTIVE: Sepsis is characterized by systemic vasodilation and hyporesponsiveness to constrictor agents, at a time when the pulmonary circulation exhibits varying degrees of vasoconstriction. Plasma endothelin-1 concentrations are increased, but the role of this potent vasoconstrictor peptide in modulating the vascular response to sepsis is unknown. Therefore, we assessed the effect of endothelin-A receptor antagonism in the response of pulmonary arteries from rats treated with lipopolysaccharide to endothelin-1, and determined the vasomotor role of the endothelin-B receptors that are known to be located on rat pulmonary artery smooth muscle and endothelium. DESIGN: Prospective, controlled study. SETTING: Animal research laboratory. SUBJECTS: Male Wistar rats (275 to 300 g). INTERVENTIONS: Animals were injected with either lipopolysaccharide (20 mg/kg i.p.) or saline (1 mL i.p.) 4 hrs before being killed. The main pulmonary arteries were cut into 2-mm rings, and suspended in an organ bath. In the first set of experiments, half of the rings underwent a procedure that removed the endothelium, and the contractile response to cumulative doses of endothelin-1 (10(-11) to 10(-6) M) was measured. Half of the rings were pretreated with the endothelin-A receptor antagonist, BQ123 (10(-5) M or 10(-6) M), and the other half of the rings were treated with vehicle. In a separate group of experiments, the contractile response to cumulative concentrations of the selective endothelin-B agonist, sarafotoxin S6c (10(-11) to 10(-6) M), was measured in rings at baseline tension. Second, the possible dilator effect of endothelin-B receptor activation was tested by the administration of sarafotoxin S6c (10(-7) to 10(-6) M) to rings preconstricted by 10(-6) M of U46619, a thromboxane receptor agonist, either in the presence or absence of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine-methylester (10(-4) M). Acetylcholine-induced (10(-4) M), endothelium-dependent vasodilation was also measured. MEASUREMENTS AND MAIN RESULTS: BQ123 (10(-5) or 10(-6) M) caused consecutive rightward shifts in the endothelin-1 concentration-contraction curves for all ring types, including the intact rings from endotoxemic animals. Sarafotoxin S6c failed to induce any direct constriction in rings from sham-treated or lipopolysaccharide-treated rats. However, sarafotoxin S6c induced transient vasodilation at the initial dose in rings from sham-treated rats but not lipopolysaccharide-treated rats-an effect that was attenuated by N omega-nitro-L-arginine-methylester. Acetylcholine induced an N omega-nitro-L-arginine-methylester-sensitive vasodilation that was reduced in rings from endotoxin-treated rats. CONCLUSIONS: Endothelin-A receptor blockade is an effective means of attenuating endothelin-1-induced contraction of isolated pulmonary artery rings, even from rats rendered endotoxemic. Endothelin-B receptors on the pulmonary artery cause vasodilation via the release of nitric oxide, and have no constrictor component. The functional effects of endothelin-B receptors on tone are lost after lipopolysaccharide treatment. The endothelium is involved in both the constrictor and dilator effects of endothelin in rat pulmonary artery, confirming a pivotal role for endothelial cells in the vascular response to sepsis.

Animals↗