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PubMed2006

Microalbuminuria: a marker of endothelial dysfunction in thermal injury.

INTRODUCTION: Systemic endothelial dysfunction (SED) and capillary leak occur following severe burn. SED can be assessed as low-level albuminuria (microalbuminuria) detectable only by sensitive immunoassay. This study compared the magnitude and duration of microalbuminuria with burn surface area and associated aggravating factors. METHODS: Serial urine specimens were collected from 2 to 36 h after injury from 43 adult burn patients with a mean total body surface area (TBSA) of 32% (range 15-68%) and during 44 episodes of wound manipulation within the same period. Urinary albumin was expressed as the albumin/creatinine ratio (ACR, normal <2.3 mg/mmol). RESULTS: Median ACR was highest 2h after injury (12.3 range 1.8-118 mg/mmol) returning to normal within 6 h. Full thickness burns (mean 17%) showed a significant association with ACR between 3 and 7h after burn. ACR was higher for up to 8 h in the presence of inhalation injury, alcohol intoxication or accelerant (p<0.05). ACR rose within 30 min of escharotomy or wound scrubbing (p<0.01). CONCLUSION: Severe burn produces variable SED which recurs with wound manipulation. Inhalation injury, alcohol intoxication and accelerant all showed a stronger association with SED than TBSA. Microalbuminuria provides a means of monitoring microvascular integrity during the early after injury period.

Adolescent↗

PubMed2006

Insertion/deletion polymorphism on ACE gene is associated with endothelial dysfunction in young patients with hypertension.

Endothelial dysfunction, insulin resistance (IR) and genetic predispositions are important risk factors of hypertension. Aim of our study was to test the hypothesis, whether insertion/deletion (I/D) polymorphism on the angiotensin converting enzyme (ACE) gene and M235T polymorphism on angiotesinogen gene (AGT) correlates with parameters of insulin sensitivity and plasminogen activator inhibitor (PAI-1) levels in newly diagnosed hypertensive patients as compared with normotensive controls. Blood pressure (BP), fasting plasma glucose, insulin, epinephrine, norepinephrine and PAI-1 concentrations were determined in 30 male patients with hypertension grade 1 (HT) and in 31 matched healthy subjects (NT). Insulin resistance was estimated using IR HOMA formula. Patients with HT had increased levels of PAI-1, norepinephrine, fasting plasma insulin levels, IR HOMA (p<0.001) compared to controls. Subjects (HT and NT) with DD and ID genotype had a significantly higher systolic BP (p<0.05) and PAI-1 compared to those with II genotype. Homozygous subjects 235T had a higher systolic BP and higher levels of epinephrine and norepinephrine than heterozygous or homozygous M235 (p<0.05). In conclusion, no association was found between M235T polymorphism and insulin resistance or PAI-1 levels, but results indicate relationship between I/D polymorphism of the ACE gene and plasma PAI-1 levels in the early stage of hypertension.

Case-Control Studies↗

PubMed2006

[Endothelial dysfunction and vasculitis: a close relationship].

Endothelial dysfunction (ECD) is implicated in the etiopathogenesis of several entities, with special interest and new perspectives in collagen diseases and vasculitis. ECD precedes development of atherosclerotic coronary damage and thrombotic events, with accelerated atherogenesis. Mechanisms of ECD that are involved in vasculitis are not simply due to focal vascular inflammation, since it may be caused by inflammatory systemic mediators, for example C reactive protein and tumor necrosis factor (TNF) alpha. We already have preliminary studies about specific ECD treatment in vasculitis, with drugs such as anti-TNF.

Endothelium, Vascular↗

PubMed2006

Abnormal flow-mediated vasodilation in normal-tension glaucoma using a noninvasive determination for peripheral endothelial dysfunction.

PURPOSE: To assess peripheral vascular endothelial function in patients with normal-tension glaucoma (NTG) by using a noninvasive method: endothelium-dependent flow-mediated vasodilation (FMD). METHODS: Forty patients with NTG and 40 healthy age- and sex-matched normal control subjects underwent measurement of FMD and endothelium-independent nitroglycerin-mediated vasodilation (NMD) via high-resolution, two-dimensional (2D) ultrasonographic imaging of the brachial artery. The patients also underwent blood sampling for biochemistry, lipid profile, and high-sensitivity C-reactive protein (hsCRP) analysis. RESULTS: The NTG group exhibited significant impairment of FMD compared with the control group (NTG: 2.64% +/- 2.22%, control: 5.96% +/- 2.50%, P < 0.001). Multivariate analysis demonstrated that the presence of NTG was the strongest independent predictor of FMD. The lipid profile and hsCRP did not differ significantly between the two groups. CONCLUSIONS: This study demonstrated impaired FMD in patients with NTG and the results provide evidence of a generalized peripheral vascular endothelial dysfunction in patients with NTG.

Blood Flow Velocity↗

PubMed2002

Abnormal carbohydrate metabolism during pregnancy : association with endothelial dysfunction.

OBJECTIVE: To evaluate whether abnormal endothelial function, a common finding in premenopausal women with type 2 diabetes, is present in early states of diabetes during pregnancy, such as impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: Brachial artery flow-mediated dilatation (FMD) (endothelium-dependent) and nitrate-induced dilatation (NID) (endothelium-independent) were measured in 23 pregnant subjects with carbohydrate abnormalities (10 IGT, 13 GDM) and in 15 pregnant control subjects during the third trimester of gestation. High-resolution vascular ultrasonography was used to perform these investigations. A fasting lipid panel was obtained, and glucose and insulin values in response to a 100-g oral glucose load were also measured. RESULTS: FMD was significantly reduced in both groups of women with abnormal carbohydrate metabolism compared with control subjects (7.6 +/- 1.1% in the IGT group and 4.1 +/- 0.9% in the GDM group vs. 10.9 +/- 1.1% in control subjects, P < 0.04 and P < 0.0001, respectively). Significant difference in FMD was also observed between IGT and GDM groups (P < 0.04). NID was comparable in the three groups. Among all subjects, FMD showed a strong independent negative correlation with glycemic area (r=-0.60, P < 0.0001). CONCLUSIONS: Endothelial dysfunction, an early marker of macrovascular disease, is present in pregnancies complicated by IGT and GDM. This alteration, which seems to be directly related to glycemic levels, could explain, at least in part, the increased risk for concurrent hypertensive disorders during pregnancy in these women.

Adult↗

PubMed2001

Endothelial dysfunction and xanthine oxidoreductase activity in rats with human renin and angiotensinogen genes.

We examined whether xanthine oxidoreductase (XOR), a hypoxia-inducible enzyme capable of generating reactive oxygen species, is involved in the onset of angiotensin (Ang) II-induced vascular dysfunction in double-transgenic rats (dTGR) harboring human renin and human angiotensinogen genes. In 7-week-old hypertensive dTGR, the endothelium-mediated relaxation of noradrenaline (NA)-precontracted renal arterial rings to acetylcholine (ACh) in vitro was markedly impaired compared with Sprague Dawley rats. Preincubation with superoxide dismutase (SOD) improved the endothelium-dependent vascular relaxation, indicating that in dTGR, endothelial dysfunction is associated with increased superoxide formation. Preincubation with the XOR inhibitor oxypurinol also improved endothelium-dependent vascular relaxation. The endothelium-independent relaxation to sodium nitroprusside was similar in both strains. In dTGR, serum 8-isoprostaglandin F(2alpha), a vasoconstrictor and antinatriuretic arachidonic acid metabolite produced by oxidative stress, was increased by 100%, and the activity of XOR in the kidney was increased by 40%. Urinary nitrate plus nitrite (NO(x)) excretion, a marker of total body NO generation, was decreased by 85%. Contractile responses of renal arteries to Ang II, endothelin-1 (ET-1), and NA were decreased in dTGR, suggesting hypertension-associated generalized changes in the vascular function rather than a receptor-specific desensitization. Valsartan (30 mg/kg PO for 3 weeks) normalized blood pressure, endothelial dysfunction, and the contractile responses to ET-1 and NA. Valsartan also normalized serum 8-isoprostaglandin F(2alpha) levels, renal XOR activity, and, to a degree, NO(x) excretion. Thus, overproduction of Ang II in dTGR induces pronounced endothelial dysfunction, whereas the sensitivity of vascular smooth muscle cells to nitric oxide is unaltered. Ang II-induced endothelial dysfunction is associated with increased oxidative stress and vascular xanthine oxidase activity.

Acetylcholine↗

PubMed2004

AKT participates in endothelial dysfunction in hypertension.

BACKGROUND: In hypertension, reduced nitric oxide production and blunted endothelial vasorelaxation are observed. It was recently reported that AKT phosphorylates and activates endothelial nitric oxide synthase and that impaired kinase activity may be involved in endothelial dysfunction. METHODS AND RESULTS: To identify the physiological role of the kinase in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), we used adenoviral vectors to transfer the human AKT1 gene selectively to the common carotid endothelium. In vitro, endothelial vasorelaxations to acetylcholine, isoproterenol, and insulin were blunted in control carotids from SHR compared with WKY rats, and human AKT1 overexpression corrected these responses. Similarly, blood flow assessed in vivo by Doppler ultrasound was reduced in SHR compared with WKY carotids and normalized after AKT1 gene transfer. In primary cultured endothelial cells, we evaluated AKT phosphorylation, activity, and compartmentalization and observed a mislocalization of the kinase in SHR. CONCLUSIONS: We conclude that AKT participates in the settings of endothelial dysfunction in SHR rats by impaired membrane localization. Our data suggest that AKT is involved in endothelium dysfunction in hypertension.

Acetylcholine↗

PubMed1999

[Endothelial dysfunction and arterial hypertension].

The endothelium lines all blood vessels in the human body, it is the basic structure which ensures the action of substances circulating in the blood stream on the vascular wall. It is an organ the sound state of which is essential for the physiological function of the vascular system. Its impaired function is a basic factor in the genesis and development of vascular disease. Under physiological conditions the endothelium has antiadhesive and antithrombotic properties, it produces vasoactive substances, prevents the penetration of circulating substances and formed elements across the vascular wall, and via adhesion molecules it participates in the interaction with cells in the circulation. Risk factors of cardiovascular diseases such as hypertension, hyperlipidaemia, hyperglycaemia, smoking damage the function of endothelial cells and cause the development of endothelial dysfunction. In patients with arterial hypertension endothelial dysfunction is characterized by an impaired endothelium dependent relaxation, increased adhesion and permeability of endothelial cells, structural changes of the vascular wall. When the endothelium is damaged by released cytokines an increased expression of adhesion molecules occurs, adhesion and migration of inflammatory cells across the vascular wall. Cytoadhesion molecules are released from the surface of the endothelium into the circulation where the rise of their plasma levels can serve as a marker of endothelial damage. Endothelial dysfunction in hypertonic subjects contributes in a significant way to the development and progression of chronic vascular disease--atherosclerosis. Improvement of the damaged endothelial function is therefore at present a desirable therapeutic objective in the treatment of hypertension.

Arteriosclerosis↗

PubMed2005

Increased plasma markers of inflammation and endothelial dysfunction and their association with microvascular complications in Type 1 diabetic patients without clinically manifest macroangiopathy.

AIMS: To evaluate whether plasma biomarkers of inflammation and endothelial dysfunction differed in Type 1 diabetic patients as compared with those in non-diabetic subjects, and to examine the association of these biomarkers with early stages of microvascular complications. METHODS: Plasma biomarkers of inflammation [fibrinogen, hs-C-reactive protein (hs-CRP)] and endothelial dysfunction [von Willebrand factor (v-WF), intercellular adhesion molecule-1, plasminogen activator inhibitor-1 (PAI-1) activity] were measured in 88 non-smoking young patients with Type 1 diabetes without clinical macrovascular disease and in 40 healthy controls. RESULTS: Plasma levels of hs-CRP, fibrinogen, v-WF, soluble intracellular adhesion molecule-1 (sICAM-1) and PAI-1 activity were markedly higher (P < 0.01 or less) in Type 1 diabetic patients than in healthy controls; these results were essentially unchanged when healthy controls were compared with patients without complications. After stratification by microvascular complication status, plasma biomarkers of inflammation and endothelial dysfunction were significantly increased in those with more advanced disease compared with those with early complications or without complications, respectively. However, while the significant differences in these biomarkers were little affected by adjustment for sex, age, BMI and blood pressure values, they were totally abolished after additional adjustment for diabetes duration and glycaemic control. CONCLUSIONS: These results indicate that in Type 1 diabetes there is a subclinical, chronic inflammation which is, at least partly, independent of clinically manifest macro- and microvascular complications, smoking or other traditional cardiovascular risk factors; this subclinical inflammation is closely correlated to the magnitude and duration of hyperglycaemia.

Adult↗

PubMed2001

Oxidative inactivation of nitric oxide and endothelial dysfunction in stroke-prone spontaneous hypertensive rats.

This study tested the hypothesis that increased nitric oxide (NO) inactivation and concurrent peroxynitrite formation is responsible for endothelial dysfunction in the spontaneously hypertensive stroke-prone rat (SHRSP). In SHRSP, the aortic vasorelaxation to acetylcholine (ACh) was decreased (p < 0.05), but NO production was unchanged. Nitrotyrosine staining, a footprint of peroxynitrite (ONOO(-)) formation, was detected. Exposure of SHRSP to a high-salt, high-fat diet (SFD) further exacerbated hypertension and accelerated end-organ disease. A severe endothelial dysfunction [maximal ACh relaxation: 49.8 +/- 2.1 versus 94.5 +/- 1.8% in Wistar-Kyoto rats (WKY), p < 0.01], increased basal NO production (482 +/- 17 versus 356 +/- 21 nM, p < 0.01), decreased ACh-stimulated NO production (57 +/- 6 versus 112 +/- 6 nM, p < 0.01), extensive inducible NO synthase and nitrotyrosine staining, elevated nitrotyrosine content (21-fold increase over WKY), and a high percentage of cells with DNA damage were observed in the aortic tissues from these animals. Treatment of SHRSP on SFD with carvedilol restored ACh-induced vasorelaxation and NO production, inhibited nitrotyrosine formation, reduced vascular cell DNA damage, and reduced end-organ injury. These data demonstrate that endothelial dysfunction was caused by increased NO inactivation alone (SHRSP) or in combination with decreased NO production from endothelial NO synthase (SHRSP on SFD). Antioxidant treatment with carvedilol exerted significant vascular protective effects, attenuated end-organ damage, and decreased mortality under these conditions.

Acetylcholine↗

PubMed2002

Ceramide-induced activation of NADPH oxidase and endothelial dysfunction in small coronary arteries.

We tested the hypothesis that ceramide induces endothelial dysfunction in small coronary arteries via NADPH oxidase-mediated superoxide and resulting peroxynitrite formation. With the use of dihydroethidium as a superoxide indicator, C(2)-ceramide was found to increase superoxide production in the endothelial cells of small coronary arteries, which was inhibited by the NADPH oxidase inhibitors N-vanillylnonanamide, apocynin, and diphenylene iodonium. NADPH oxidase expression was confirmed in endothelial cells, as indicated by the immunoblotting of its subunits gp91(phox) and p47(phox). C(2)-ceramide increased NADPH oxidase activity by 52%, which was blocked by NADPH oxidase inhibitors but not by inhibitors of NO synthase, xanthine oxidase, and mitochondrial electron transport chain enzymes. By Western blot analysis, ceramide-induced NADPH oxidase activation was found to be associated with the translocation of p47(phox) to the membrane. In isolated and pressurized small coronary arteries, N-vanillylnonanamide, apocynin, or uric acid, a peroxynitrite scavenger, largely restored the inhibitory effects of ceramide on bradykinin- and A-23187-induced vasorelaxation. With the use of nitrotyrosine as a marker, C(2)-ceramide was found to increase peroxynitrite in small coronary arteries, which could be blocked by uric acid. We conclude that NADPH oxidase-mediated superoxide production and subsequent peroxynitrite formation mediate ceramide-induced endothelial dysfunction in small coronary arteries.

Animals↗

PubMed2004

Endothelial dysfunction in congestive heart failure: ACE inhibition vs. angiotensin II antagonism.

BACKGROUND: Endothelial dysfunction of the vasculature contributes to the elevated peripheral resistance and reduced myocardial perfusion in congestive heart failure (CHF). The present study systematically investigated the effect of angiotensin II (AT(1))- receptor blockade on vascular superoxide (O(2)(-)) production and endothelial dysfunction. METHODS AND RESULTS: Vasodilator responses and O(2)(-) production were determined in aortic rings from Wistar rats with experimental CHF 10 weeks after extensive myocardial infarction and compared with sham-operated animals (Sham). Rats were either treated with placebo (P), with the AT(1)-receptor antagonist Irbesartan (50 mg kg(-1) day(-1)) or with the ACE inhibitor Trandolapril (0.3 mg kg(-1) day(-1)). In CHF-P, endothelium-dependent, acetylcholine-induced relaxation was significantly attenuated compared with Sham-P. Chronic treatment with Trandolapril or Irbesartan significantly improved endothelium-dependent relaxation. Aortic O(2)(-) formation was markedly increased in CHF, and was not significantly affected by Trandolapril treatment, while it was reduced by Irbesartan. eNOS expression was reduced in CHF and normalised by both treatments. CONCLUSION: Endothelial vasomotor function in CHF rats was normalised by long-term treatment with an ACE inhibitor or an AT(1)-antagonist. Reduced aortic eNOS expression was normalised by both treatments, whereas aortic superoxide formation was only reduced by the AT(1)-antagonist Irbesartan.

Analysis of Variance↗

PubMed2000

Hypercholesterolemia increases coronary endothelial dysfunction, lipid content, and accelerated atherosclerosis after heart transplantation.

Hyperlipidemia may increase endothelial damage and promote accelerated atherogenesis in graft coronary vasculopathy. To study the effects of hypercholesterolemia on coronary endothelial dysfunction, intimal hyperplasia, and lipid content, a porcine model of heterotopic heart transplantation, allowing nonacute rejection without immunosuppressive drugs, was used. A high cholesterol diet was fed to donor and recipient swine 1 month before and after transplantation. The endothelial function of coronary arteries of native and transplanted hearts from cholesterol-fed animals was studied in organ chambers 30 days after implantation and compared with endothelial function in arteries from animals fed a normal diet. The total serum cholesterol increased 3-fold in donors and recipients. Endothelium-dependent relaxations to serotonin, to the alpha(2)-adrenergic agonist UK14,304, and to the direct G-protein activator sodium fluoride were decreased significantly in allografted hearts compared with native hearts from both groups. Relaxations to the calcium ionophore A23187 and bradykinin were decreased significantly in allografts from animals fed the high cholesterol diet. The prevalence of intimal hyperplasia was significantly increased in coronary arteries from hypercholesterolemic swine. There was a significant increase in the lipid content of allograft arteries of hypercholesterolemic recipients. Hypercholesterolemia causes a general coronary endothelial dysfunction, increases the prevalence of intimal hyperplasia, and augments the incorporation of lipids in the vascular wall after heart transplantation. Hyperlipidemia accelerates graft coronary atherosclerosis through its effects on the endothelium.

Adrenergic alpha-Agonists↗

PubMed2004

Inflammation, endothelial dysfunction, and platelet activation in patients with chronic kidney disease: the chronic renal impairment in Birmingham (CRIB) study.

BACKGROUND: Studies in the general population suggest that low-grade inflammation, endothelial dysfunction, and platelet activation are associated with an increased risk of cardiovascular events. METHODS: Markers of inflammation, endothelial dysfunction, and platelet activation were measured in 334 patients with chronic kidney disease (serum creatinine >1.47 mg/dL [>130 micromol/L] at screening) and compared with 2 age- and sex-matched control groups, 1 comprising 92 patients with coronary artery disease and the other comprising 96 apparently healthy individuals with no history of cardiovascular or kidney disease. RESULTS: There was evidence of low-grade inflammation in the chronic renal impairment group compared with healthy controls, with higher concentrations of C-reactive protein (3.70 versus 2.18 mg/L, P < 0.01) and fibrinogen (3.48 versus 2.67 g/L, P < 0.001) and lower serum albumin concentration (41.8 versus 44.0 g/dL [418 versus 440 g/L], P < 0.001). More severe renal impairment was associated with a trend towards higher fibrinogen and lower albumin concentrations (both P < 0.001), although there was no association with higher C-reactive protein level. As compared to healthy controls, plasma von Willebrand factor (142 versus 108 IU/dL, P < 0.001) and soluble P-selectin concentrations (57.0 versus 43.3 ng/mL, P < 0.001) were also higher in the chronic renal impairment group. More severe renal impairment was associated with a trend towards higher levels of von Willebrand factor (P < 0.001) and of soluble P selectin (P < 0.05). CONCLUSION: This cross-sectional analysis demonstrates that chronic kidney disease is associated with low-grade inflammation, endothelial dysfunction, and platelet activation, even among patients with moderate renal impairment.

Adult↗

PubMed1999

Ischemic preconditioning attenuates postischemic coronary artery endothelial dysfunction in a model of minimally invasive direct coronary artery bypass grafting.

OBJECTIVE: Unmodified reperfusion without cardioplegia in minimally invasive direct coronary artery bypass grafting procedures causes endothelial dysfunction that may predispose to polymorphonuclear neutrophil-mediated myocardial injury. This study tested the hypothesis that ischemic preconditioning in a minimally invasive direct coronary artery bypass grafting model attenuates postischemic endothelial dysfunction in coronary vessels. METHODS: In anesthetized dogs, the left anterior descending coronary artery was occluded for 30 minutes and reperfused for 3 hours without ischemic preconditioning (no-ischemic preconditioning; n = 7); in 7 dogs, the left anterior descending occlusion was preceded by 5 minutes occlusion followed by 5 minutes of reperfusion. Relaxation responses to stimulators of nitric oxide synthase were used to evaluate endothelial function in arteries from the ischemic-reperfused (left anterior descending) and nonischemic (left circumflex coronary artery) zones. RESULTS: Stimulated endothelial-dependent relaxation of epicardial left anterior descending artery to incremental concentrations of acetylcholine in the no-ischemic preconditioning animals was shifted to the right, and maximal relaxation was attenuated compared with the nonischemic left circumflex coronary artery (117% +/- 4% vs 138% +/- 5%). In contrast, acetylcholine-induced maximal relaxation was comparable in the left anterior descending artery versus left circumflex coronary artery in the ischemic preconditioning group (130% +/- 6% vs 135% +/- 5%). In 150- to 200- microm left anterior descending microvessels, 50% relaxation occurred with a lower concentration (log[M]) of acetylcholine in ischemic preconditioning versus no-ischemic preconditioning (-8.0 +/- 0.4 vs -7.0 +/- 0.1) with no group differences in smooth muscle relaxation to sodium nitroprusside, suggesting endothelial-specific damage. Adherence of fluorescent labeled polymorphonuclear neutrophils to epicardial coronary artery endothelium, used as an index of basal (unstimulated) anti-polymorphonuclear neutrophil function, was significantly attenuated by ischemic preconditioning versus no-ischemic preconditioning (293 +/- 25 polymorphonuclear neutrophils/mm2 vs 528 +/- 29 polymorphonuclear neutrophils/mm2). CONCLUSION: In this minimally invasive direct coronary artery bypass grafting model, both agonist-stimulated and basal postischemic endothelial dysfunction were attenuated by ischemic preconditioning.

Analysis of Variance↗

PubMed2004

Diabetes is a vascular disease: the role of endothelial dysfunction in pathophysiology of cardiovascular disease in diabetes.

Diabetes is a vascular disease. Endothelial dysfunction is the initial process in vascular manifestations of diabetes mellitus (DM). There are multiple pathways involved in the pathophysiologic process related to endothelial dysfunction in DM. Most of these abnormalities occur secondary to insulin resistance. In this article the role of insulin, glucose,dyslipidemia, oxidative stress and various cellular mechanisms related to endothelial dys-function in diabetes are discussed in detail.

Cardiovascular Diseases↗

PubMed2005

Isoflurane prevents platelets from enhancing neutrophil-induced coronary endothelial dysfunction.

We evaluated whether platelets can enhance polymorphonuclear neutrophil-induced coronary endothelial dysfunction, and, after observing this, whether isoflurane can prevent the effect. Neutrophils, coronary artery segments, and platelets were obtained from 25 healthy dogs. Coronary artery rings were exposed to neutrophils activated with platelet-activating factor (1.0 microM), and after washing and preconstriction with U46619, were evaluated for concentration-related responses to acetylcholine, an endothelium-dependent vasorelaxing drug. Superoxide production by activated neutrophils was measured spectrophotometrically. Adherence of the activated neutrophils to the endothelium of coronary segments was assessed by direct counting of neutrophils labeled with fluorescent dye. Measurements were performed in absence and presence of isoflurane (1 minimum alveolar concentration) both with and without platelets. The presence of platelets enhanced the neutrophil-induced rightward shift in the concentration-vasorelaxation response curve to acetylcholine (the concentration of acetylcholine required to elicit 50% of maximal relaxation (-log M) was increased from 6.78 +/- 0.7 to 5.26 +/- 0.6), and it increased superoxide oxide production from 45.0 +/- 4.2 to 54.3 +/- 4.2 nM O2-/5 x 10(6) neutrophils and adherence of activated neutrophils from 204 +/- 10 to 268 +/- 5 neutrophils/mm2. Isoflurane abolished these effects of platelets. In conclusion, platelets enhanced the ability of neutrophils to cause coronary endothelial dysfunction. This effect was prevented by isoflurane. This may be attributable to an inhibitory action on superoxide production by the neutrophils leading to reduced expression of endothelial adhesion molecules and, in turn, reduced neutrophil adherence.

Acetylcholine↗

PubMed2026

The Association Between NT-Pro BNP, Nephropathy and Endothelial Dysfunction in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-Pro BNP) is an established biomarker of heart failure and has been recommended for cardiovascular risk stratification in type 2 diabetes mellitus (T2DM). However, its relationship with diabetic nephropathy and endothelial dysfunction across varying stages of kidney impairment remains unclear. This study examined the associations of NT-Pro BNP, renal impairment, albuminuria and endothelial dysfunction in patients with T2DM without overt heart failure. METHODS: A comparative cross-sectional study was conducted among 192 adults with T2DM. Participants were stratified by KDIGO eGFR groups (≥ 90, 60-89, 30-59 mL/min/1.73m2). NT-Pro BNP was considered abnormal at a cut-off of ≥ 125 pg/mL. Albuminuria was categorized using the urinary albumin-to-creatinine ratio (uACR). Endothelial function was assessed by brachial artery flow-mediated dilatation (FMD). Logistic regression analysis was performed to identify independent factors of elevated NT-Pro BNP, with p-values < 0.05 considered statistically significant. RESULTS: NT-Pro BNP levels were significantly higher in the lower eGFR groups compared with normal eGFR (204.3 vs. 96.8 vs. 62.2 pg/mL, p < 0001). A weak but significant positive correlation was observed between NT-Pro BNP and uACR (r = 0.31, p < 0.001). However, no significant association was found between NT-Pro BNP and FMD (p = 0.388). Following multivariable adjustments, older age (adjusted OR 1.14, 95% CI: 1.06-1.23, p < 0.001), higher systolic blood pressure (adjusted OR 1.05, 95% CI: 1.02-1.08, p = 0.010), lower eGFR (adjusted OR 0.97, 95% CI: 0.95-0.99, p = 0.003) and beta-blocker use (adjusted OR 4.65, 95% CI: 1.61-13.45, p < 0.001) were independently associated with elevated NT-Pro BNP. CONCLUSION: In patients with T2DM without overt heart failure, elevated NT-Pro BNP showed a statistically significant association with lower eGFR and higher albuminuria. Moderate to severe albuminuria becomes an independent factor for elevated NT-Pro BNP after adjustment excluding eGFR. The lack of association with endothelial dysfunction suggests that NT-Pro BNP may reflect different pathophysiological pathways. NT-Pro BNP may serve as a useful biomarker for early cardiovascular risk stratification and identification of individuals at risk of pre-heart failure in diabetic kidney disease.

NT‐Pro BNP↗