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PubMed2002

Inhibition of mitogen-activated protein/extracellular signal-regulated kinase improves endothelial function and attenuates Ang II-induced contractility of mesenteric resistance arteries from spontaneously hypertensive rats.

OBJECTIVES: Extracellular signal-regulated kinases (ERK1/2) modulate vascular smooth muscle cell (VSMC) growth and contractility, important factors in blood pressure regulation. In the present in vivo study, we investigated whether short-term inhibition of ERK1/2-dependent signaling pathways influences vascular function and blood pressure (BP) in spontaneously hypertensive rats (SHR). METHODS: SHR and Wistar-Kyoto (WKY) rats were injected subcutaneously with either PD98059, selective MEK1/2 inhibitor (20 mg/kg), or vehicle. BP was measured by telemetry. Rats were killed 24 h after injection and small mesenteric arteries mounted as pressurized systems for morphometric analysis and assessment of endothelial function and angiotensin II (Ang II)-induced contractility. ERK1/2 phosphorylation was measured by Western blots, using protein extracts from mesenteric arteries, aorta, heart and kidneys. RESULTS: BP was higher (P < 0.01) in SHR than in WKY rats. PD98059 did not influence BP in either group. Endothelial-dependent relaxation (acetylcholine-induced), which was impaired in SHR, was improved by PD98059 (P < 0.05). Ang II increased contraction, with greater responses in SHR (Emax = 25 +/- 4%) than WKY (Emax = 9 +/- 3%) (P < 0.01). PD98059 reduced Ang II-induced contraction in SHR (Emax = 5.8 +/- 0.4%) and WKY (Emax = 4 +/- 0.4%). Vascular structure was unaltered by PD98059. Vascular and renal ERK1/2 phosphorylation, which was higher in SHR than WKY, was decreased by PD98059 in SHR. CONCLUSION: Short-term treatment with PD98059 improves endothelial function and vascular contractility without influencing BP in SHR. These findings provide evidence that vascular ERK1/2 activity is upregulated and that MEK1/2-sensitive signaling pathways play an important role in the regulation of vascular function in SHR. Acute inhibition of MEK1/2 does not alter blood pressure despite improved endothelial function and reduced arterial reactivity to Ang II.

Angiotensin II↗

PubMed2001

Acute effects of haemodialysis on endothelial function and large artery elasticity.

BACKGROUND: Disturbances of functional properties of large arteries contribute to increased cardiovascular morbidity and mortality in patients with end-stage renal disease. However, it is not clear whether haemodialysis per se acutely affects mechanical vessel wall properties or endothelial function. METHODS: Twenty-five chronic haemodialysis patients (mean+/-standard error of the mean (SEM): age 52+/-5 years; time on dialysis 63+/-7 months; blood pressure 132+/-4/72+/-2 mmHg) were studied before and immediately after a haemodialysis (HD) session using a polysulphone dialyser (ultrafiltration 1460+/-54 ml), as well as on the following day. Blood pressure was measured with an automatic sphygmomanometer and applanation tonometry. End-diastolic diameter and distension of the brachial and carotid arteries were measured by Doppler frequency analysis of vessel wall movements in M-mode using a multigate pulsed Doppler system and aortic pulse wave velocity (PWV) by an automatic device (Complior). Endothelial function was determined as brachial artery flow-mediated dilation (FMD) and compared with endothelium-independent nitroglycerine-induced dilation (NMD). RESULTS: FMD was 7.9+/-1.8% in patients before HD and did not change significantly after HD or in the dialysis-free intervall (6.7+/-2.1 and 7.1+/-2.0%, respectively; NS). The same was true for NMD and PWV (12.6+/-0.8 m/s before HD, 12.8+/-0.8 m/s after HD, and 11.9+/-0.7 m/s on the HD-free day). Carotid distensibility coefficients decreased significantly during HD (from 18.1+/-1.9 x 10(-3)/kPa to 16.7+/-2.2 x 10(-3)/kPa, P<0.05) and increased again on the HD-free day (19.8+/-2.4 x 10(-3)/kPa). However, when corrected for blood pressure by tonometry, isobaric carotid distensibility did not change significantly. Brachial artery distensibility also did not show significant acute changes. CONCLUSIONS: Haemodialysis per se did not have a significant effect on endothelial function or large artery mechanical vessel wall properties in patients on maintenance dialysis therapy.

Arteries↗

PubMed1997

Effect of a single high-fat meal on endothelial function in healthy subjects.

Although there is a well-established relation between serum cholesterol and coronary artery disease risk, individual and national variations in this association suggest that other factors are involved in atherogenesis. High-fat diet associated triglyceride-rich lipoproteins have also been suggested to be atherogenic. To assess the direct effect of postprandial triglyceride-rich lipoproteins on endothelial function, an early factor in atherogenesis--10 healthy, normocholesterolemic volunteers--were studied before and for 6 hours after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat, respectively). Endothelial function, in the form of flow-mediated vasoactivity, was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum lipoproteins and glucose were determined before eating and 2 and 4 hours postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and 10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p <0.05 compared with low-fat meal data). No changes in lipoproteins or flow-mediated vasoactivity were observed after the low-fat meal. Fasting low-density lipoprotein cholesterol correlated inversely (r = -0.47, p = 0.04) with preprandial flow-mediated vasoactivity, but triglyceride level did not. Mean change in postprandial flow-mediated vasoactivity at 2, 3, and 4 hours correlated with change in 2-hour serum triglycerides (r = -0.51, p = 0.02). These results demonstrate that a single high-fat meal transiently impairs endothelial function. These findings identify a potential process by which a high-fat diet may be atherogenic independent of induced changes in cholesterol.

Adult↗

PubMed1989

Disturbances of reticulo-endothelial function following experimental liver transplantation.

Reticulo-endothelial function was studied in liver-grafted pigs using intravenous carbon clearance at 24 h and 7 days postgraft. Flushing of auto- or allografts with Ringer's lactate and with or without 4-hour storage caused no change in carbon clearance. Flushing of auto- or allografts with Eurocollins solution and with or without 4-hour storage resulted in delayed carbon clearance at 7 days. The changes appeared to be related to the composition of preservation fluid rather than to its volume or temperature, the duration of storage or the development of rejection.

Animals↗

PubMed2004

[Ultrasound assessment of endothelial function in Chilean children and adults].

BACKGROUND: Endothelial dysfunction is an important pathogenetic mechanism in the development of atherosclerosis. AIM: To evaluate endothelial function in Chilean children and adult subjects and to provide normal values of flow mediated dilatation (FMD) in the Chilean population. SUBJECTS AND METHODS: Flow mediated dilation of the brachial artery was measured by high resolution ultrasonography in healthy children (n=32) and adults (n=69) of both gender, in a group of 8 healthy women during 4 periods of pregnancy and late postpartum, and in 22 men and women with a history of stroke or coronary heart disease. RESULTS: FMD in boys and girls was 9.9 +/- 3.6 and 10.0 +/- 4.2% respectively (NS). The figures for young women and young men were 11.3 +/- 3.8 and 8.6 +/- 3.9, respectively (p=0.02); for postmenopausal women and older men, 5.5 +/- 6.6 and 7.6 +/- 6.7 respectively (NS). During normal pregnancy and postpartum there were no significant changes in FMD. Patients with cardiovascular disease had a FMD of 0.3 +/- 5.2%, (p <0.001, with other groups). CONCLUSIONS: The present study provides values of FMD in healthy Chilean subjects of different ages, and in patients with coronary heart disease.

Adolescent↗

PubMed2004

The effect of hormone replacement therapy on endothelial function in postmenopausal women with hypertension.

BACKGROUND: Endothelial dysfunction has been implicated in the pathophysiology of cardiovascular diseases, including arterial hypertension. The present study was undertaken to assess endothelial function in postmenopausal women with arterial hypertension receiving hormone replacement therapy and antihypertensive treatment. MATERIAL/METHODS: A group of 76 women with natural menopause and essential mild to moderate arterial hypertension entered the study. Forty women received a transdermal, combined hormone replacement therapy (HRT) of 17 -estradiol and norethisterone acetate, whereas 36 served as controls. At baseline and at 3 and 12 months, all patients underwent 24-hr blood pressure monitoring and an exercise test, before which, at peak exercise, and after a 15-min recovery period venous blood was drawn to measure the level of nitrite/nitrate (NOx) according to the Griess RESULTS: At 3 and 12 months after beginning HRT, the level of NOx at rest was slightly increased, with marked individual differences in response to HRT. In women not receiving HRT, NOx did not change. In the HRT group, 52.5% at 3 months and 47.5% at 12 months had significantly increased levels compared with the baseline values (17.8+/-6.7 vs. 32.8+/-4.5 vs. 28.7+/-1.1 Kmol/l; p=0.002). The increased NOx level in responders was associated with decreased LDL cholesterol (3.62+/-1.2 vs. 3.53+/-1.3 vs. 2.6+/-0.6 mmol/l; p=0.01). At 12 months, blood pressure values did not differ from those at baseline in either group. CONCLUSIONS: The significant increase of NOx in half of the women receiving HRT suggests that only responders experience the cardioprotective effects of HRT.

Administration, Cutaneous↗

PubMed2003

Increased vasoconstrictor reactivity and decreased endothelial function in high grade varicocele; functional and morphological study.

The pathophysiology of human varicocele is not fully understood. We investigated vasoconstrictor reactivity, endothelial function and morphological changes in different grades of varicocele to clarify the pathophysiology. Contractile responses to phenylephrine, norepinephrine, serotonin and histamine were determined in isolated human varicose spermatic veins using the organ bath technique. Endothelial function was tested with acetylcholine-induced relaxation after phenylephrine-induced precontraction in the absence and presence of nitric oxide synthase inhibitor, L-NAME, and cyclooxygenase inhibitor, indomethacin. The cyclic guanosine monophosphate (cGMP) level was measured in the spermatic vein and peripheral plasma. Morphological changes were evaluated with light microscopy. Phenylephrine, norepinephrine, serotonin and histamine induced concentration-dependent contractions. The maximum contractions for all of these agents except norepinephrine were significantly higher in grade III than grade I and II (P<0.05). The sensitivity to phenylephrine was significantly higher in grades II and III than in grade I (P<0.05). In the presence of L-NAME and indomethacin, the difference from respective control phenylephrine-induced contractions was higher in grade I and II than grade III. Acetylcholine did not induce stable relaxation but the level of cGMP, which is responsible for the vasorelaxant effect of NO, in veins was lower in grades II and III than grade I (P<0.05). Vessel wall thickness increased in grade II and dilatation developed in grade III when compared to grade I (P<0.05). Our findings suggest that endothelium produces less vasorelaxant which results in the more enhanced effects of vasoconstrictor substances in grade III, indicating that endothelial dysfunction develops at high grades of varicocele.

Endothelium, Vascular↗

PubMed2006

Endothelial function parameters in patients with unstable angina and infection with Helicobacter pylori and Chlamydia pneumoniae.

BACKGROUND: Endothelial dysfunction may be a factor linking infection with atherosclerosis. The aim of our study was to assess the relationship between seropositivity to Helicobacter pylori (Hp) and/or to Chlamydia pneumoniae (Cp) and some endothelial function parameters in patients with unstable angina. METHODS: In 31 patients with unstable angina, we determined the serum concentration of the von Willebrand factor (vWF), thrombomodulin, tissue plasminogen activator antigen, and tissue plasminogen activator inhibitor type 1 antigen, the concentration of IgG antibodies to Hp and Cp (all by ELISA), and the level of C-reactive protein. The Western blot test was performed for all patients seropositive to Hp. It allowed us to identify 15 different antigen proteins of Hp. RESULTS: Sixty-one percent of the patients were seropositive to both Hp and Cp, and 35% were seropositive to Hp only. We did not find significant differences in serum concentrations of endothelial function parameters and CRP between the two groups of patients. The patients seropositive to both Hp and Cp had a significantly higher serum concentration of vWF when Hp did not contain the 95 kDa protein (p=0.01) and a significantly higher serum concentration of PAI-1:Ag when Hp did not contain the 57 kDa protein (p=0.002) and the 66 kDa protein (p=0.02). CONCLUSION: The results show that the antigenic profile of bacteria may play a more significant role in coronary artery disease than seropositivity.

Journal Article↗

PubMed2005

Endothelial function markers in parkinsonian patients with hyperhomocysteinemia.

Hyperhomocysteinemia is considered a risk factor for vascular disease causing endothelial damage and consequently atherogenesis. The purpose of this study was to investigate the effect of elevated homocysteine on certain biochemical markers of endothelial function in patients with idiopathic Parkinson's disease (PD). Blood homocysteine levels were assessed in 57 PD patients and 40 matched normal controls. Investigation of the C677T 5,10 methylenetetrahydrofolate reductase (MTHFR) genotype was also performed in 43 PD patients. The following markers of endothelial function were assessed: superoxide dismutase (SOD), nitric oxide (NO), sICAM-1 and sE-selectin. Homocysteine levels were found mildly elevated in PD patients particularly in those treated with L-Dopa. MTHFR genotype did not influence significantly this finding. SOD activity was found reduced but it was not correlated to homocysteine levels. All other parameters measured were normal and were not related to hyperhomocysteinemia. Our findings indicate that mild hyperhomocysteinemia in PD patients was not associated with endothelial dysfunction.

Aged↗

PubMed2003

Effect of lower dosage of oral conjugated equine estrogen on inflammatory markers and endothelial function in healthy postmenopausal women.

OBJECTIVE: Although oral estrogen replacement therapy (ERT) in postmenopausal women improves endothelial function, it also increases plasma C-reactive protein (CRP) and interleukin-6 (IL-6) concentration. The proinflammatory effect of oral ERT may explain the increased risk of coronary heart disease (CHD) associated with this treatment. Recent observational studies have demonstrated that a lower dose of oral estrogen reduces the risk for CHD. The purpose of the present study was to investigate the effects of low-dose oral estrogen on vascular inflammatory markers and endothelium-dependent vasodilation in postmenopausal women. METHODS AND RESULTS: Postmenopausal women were randomized into 3 groups to receive no treatment (n=14) or oral conjugated equine estrogen (CEE) at a dosage of 0.625 mg (n=15) or 0.3125 mg (n=15) daily for 3 months. CEE at a dosage of 0.625 mg resulted in significant increases in plasma concentrations of CRP from 690.9+/-749.5 to 1541.9+/-1608.0 ng/mL, serum amyloid A from 6.12+/-4.15 to 8.25+/-4.40 microg/mL, and IL-6 from 1.45+/-0.73 to 2.35+/-1.16 pg/mL. In contrast, CEE at a dosage of 0.3125 mg had no effect on these inflammatory markers. Both dosages of estrogen significantly decreased E-selectin concentration, whereas the concentrations of intercellular and vascular cell adhesion molecules remained unchanged. In both CEE groups, flow-mediated vasodilation in the brachial artery was increased significantly, whereas nitroglycerine-induced vasodilation was unaltered. CONCLUSIONS: Oral CEE at a low dose of 0.3125 mg in postmenopausal women eliminated the adverse effects of high-dosage oral CEE on vascular inflammatory markers in addition to preserving the favorable effects of estrogen on cell adhesion molecules and endothelial function.

Administration, Oral↗

PubMed2005

Dietary soy isoflavone induced increases in antioxidant and eNOS gene expression lead to improved endothelial function and reduced blood pressure in vivo.

Epidemiological evidence suggests that populations consuming large amounts of soy protein have a reduced incidence of coronary heart disease (1-5). The cardiovascular risks associated with conventional hormone replacement therapy in postmenopausal women (5-7) have precipitated a search for alternative estrogen receptor modulators. Here we report that long-term feeding of rats with a soy protein-rich (SP) diet during gestation and adult life results in decreased oxidative stress, improved endothelial function, and reduced blood pressure in vivo measured by radiotelemetry in aged male offspring. Improved vascular reactivity in animals fed an SP diet was paralleled by increased mitochondrial glutathione and mRNA levels for endothelial nitric oxide synthase (eNOS) and the antioxidant enzymes manganese superoxide dismutase and cytochrome c oxidase. Reduced eNOS and antioxidant gene expression, impaired endothelial function, and elevated blood pressure in animals fed a soy-deficient diet was reversed after refeeding them an SP diet for 6 months. Our findings suggest that an SP diet increases eNOS and antioxidant gene expression in the vasculature and other tissues, resulting in reduced oxidative stress and increased NO bioavailability. The improvement in endothelial function, increased gene expression, and reduced blood pressure by soy isoflavones have implications for alternative therapy for postmenopausal women and patients at risk of coronary heart disease.

Animal Feed↗

PubMed2006

Relationship between chronic tadalafil administration and improvement of endothelial function in men with erectile dysfunction: a pilot study.

Men with erectile dysfunction (ED) frequently have a disproportionate burden of comorbid vascular disorders including atherosclerotic disease. We investigated whether scheduled tadalafil is better than on-demand (OD) in improving endothelium-dependent vasodilatation of cavernous arteries in men with ED and whether this effect is also exerted on markers of endothelial function. We did an open-label, randomized, crossover study including 20 male outclinic patients aged 18 years or older (mean age 54 years) who had at least a 3-month history of ED of any severity or etiology. Tadalafil (20 mg) on alternate days (ADs) or OD was administered for 4 weeks. Primary end points were variations of basal inflow (peak systolic velocity (PSV)) and flow-mediated dilatation (FMD) of cavernous arteries compared with baseline at penile Duplex ultrasound. Secondary end points were variations of Q13-SIEDY scores regarding morning erections and of markers of endothelial function, that is, vascular cell adhesion molecule (VCAM), intercellular cell adhesion molecule, endothelin-1 (ET-1), insulin and C-reactive protein (CRP). PSVs and FMD were higher after AD treatment when compared with OD and baseline, respectively (P=0.0001), and improvements were maintained from 2 weeks after discontinuation (P<0.005). Patients receiving tadalafil AD experienced a significant improvement of morning erections as compared to AD treatment (P<0.0001); ET1, VCAM and CRP showed a robust decrease after chronic vs OD regimes (P<0.05), with concomitant increase in insulin levels (P<0.05), without any variation in blood pressure and other laboratory parameters. Chronic but not OD tadalafil improves endothelial function with sustained effects from its discontinuation. Chronic treatment also produces a dramatic increase in morning erections, which determines better oxygenation to the penis, thus providing a rationale for vascular rehabilitation.

Biomarkers↗

PubMed2003

No effect of an L-arginine-enriched medical food (HeartBars) on endothelial function and platelet aggregation in subjects with hypercholesterolemia.

BACKGROUND: Providing L-arginine as a precursor for nitric oxide has been proposed to improve endothelial function in populations at high risk for cardiovascular events. We studied the effects of dietary L-arginine supplementation with HeartBars (a medical food rich in L-arginine, Cooke Pharma, Belmont, Calif) on flow-mediated dilation and markers of endothelial function in subjects with hypercholesterolemia. METHODS: We randomly assigned 47 subjects with hypercholesterolemia to receive one HeartBar containing 3.3 g L-arginine each, or a placebo bar, consumed twice daily for 2 weeks. Flow-mediated dilation, platelet aggregation studies, and soluble levels of endothelial and platelet adhesion molecules were obtained before and after the 2-week treatment period. RESULTS: Baseline and follow-up levels of L-arginine were 78.5 +/- 28.2 micromol/L and 80.7 +/- 26.7 micromol/L, respectively (P =.54). The HeartBar group had no improvement in flow-mediated dilation; changes in brachial artery diameter at baseline and follow-up were 5.52% +/- 3.32% and 4.96% +/- 2.39%, respectively. There were also no changes in the soluble levels of E-selectin and P-selectin by treatment group. CONCLUSIONS: In our study, 2 weeks of HeartBar supplementation in subjects with hypercholesterolemia showed no favorable effects on endothelial or platelet function.

Ambulatory Care↗

PubMed1996

Impaired endothelial function with essential hypertension assessed by ultrasonography.

The objective of this investigation was to evaluate the role of hypertension in endothelial function, changes in which are known to be an early event of atherosclerosis. We assessed endothelial function in 13 subjects with normal blood pressure and 13 subjects with essential hypertension who had never been treated for hypertension or hyperlipidemia and who had no history of smoking or coronary or cerebrovascular disease. B-mode ultrasonography was used to measure the diameter of the brachial artery. Endothelium-dependent dilatation was assessed as the change in diameter of the artery during reactive hyperemia. Endothelium-independent dilatation was evoked, as a control, by sublingual administration of isosorbide dinitrate. Despite similar ages and lipid and glucose levels in the study groups, endothelium-dependent dilatation was less in patients with hypertension (13.1% +/- 1.6%) than in subjects with normal blood pressure (18.5% +/- 1.9%) (p < 0.05), whereas isosorbide dinitrate-induced changes were similar. Systolic and diastolic blood pressure were significantly correlated with endothelium-dependent vasodilatation (r = -0.57 and r = -0.53, respectively) but not with the change by isosorbide dinitrate. These results suggest that endothelial dysfunction exists in patients with hypertension and precedes overt atherosclerotic disease.

Adult↗

PubMed1998

Verapamil plus nitroglycerin solution maximally preserves endothelial function of the radial artery: comparison with papaverine solution.

BACKGROUND: Endothelium plays a key role in graft patency. My colleagues and I have developed a verapamil+nitroglycerin solution (balanced to pH 7.4) to prepare the radial artery without mechanical distention or dilation and have reported the efficacy of its antispastic action. This study was designed to investigate whether using this solution as part of the University of Hong Kong protocol to prepare the radial artery is more efficacious than papaverine solution in preserving endothelial function. METHODS: Ring segments of the radial artery taken from 25 patients undergoing coronary artery bypass grafting were studied in organ chambers. The endothelium-dependent relaxation, as the index of endothelial function, was examined by two mechanisms-receptor-mediated relaxation (by acetylcholine) and non-receptor-mediated relaxation (by calcium ionophore A23187) in U46619-induced contraction (10 nmol/L). RESULTS: In the relaxation induced by either acetylcholine (27.3% +/- 5.0% [n = 7] vs 23.9% +/- 3.9% [n = 6],p = 0.6) or A23187 (62.9% +/- 6.0% [n = 13] vs 62.3% +/- 8.4% [n = 6],p = 0.96), there was no significant difference between the control radial arteries and those treated with the verapamil+nitroglycerin solution. In the papaverine-treated rings, acetylcholine-mediated relaxation was abolished (3.3% +/- 2.6% vs 23.9% +/- 3.9%,p < 0.001) and A23187-mediated relaxation was significantly reduced (39.7% +/- 5.2% vs 62.3% +/- 8.4%, p = 0.02) compared with verapamil+nitroglycerin treatment. CONCLUSION: Use of verapamil+nitroglycerin solution to prepare the radial artery maximally preserves endothelial function. In contrast, papaverine impairs this function. Verapamil+nitroglycerin solution may be effectively and safely used to prepare the radial artery for coronary artery bypass grafting.

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

PubMed2006

Impact of paraoxonase polymorphism (Q192R) on endothelial function in intact coronary circulation.

Paraoxonase-1 (PON1) can protect endothelial function by preventing the oxidation of low-density lipoprotein (LDL) cholesterol and retarding the development of atherosclerosis. We examined whether PON1 polymorphism influences endothelium-dependent coronary vasomotor responses. Sixty-seven patients underwent diagnostic cardiac catheterization, but showed no significant coronary artery stenosis. In all patients, PON1 genotypes (Q/Q, Q/R and R/R) were determined, and provocative testing was performed by the intracoronary administration of graded doses of bradykinin (BK; 0.2, 0.6 and 2.0 mug/min) and acetylcholine (ACh; 3, 10 and 30 mug/min). Coronary blood flow (CBF) was evaluated by a Doppler guide wire. The patients were divided into 2 groups on the basis of ACh testing: one with coronary spastic angina (CSA) and one with non-CSA. The frequencies of the PON1 genotype in the CSA group did not differ significantly from those in the non-CSA group. In the non-CSA group, the patients were subdivided into 2 groups: a group with the Q/Q or Q/R genotypes and a group with the R/R genotype. The vasoconstrictive responses of the epicardial coronary artery to ACh were comparable between the Q/Q + Q/R and R/R groups. Also, the coronary vasodilations induced by BK in the R/R group were similar to those in the QR + QQ group. There were no significant differences in the CBF responses induced by BK or ACh between the Q/Q + Q/R and R/R groups. In conclusion, as estimated by BK and ACh testing, our findings suggest that PON1 genotypes may not play a critical role in the modulation of endothelial vasomotor function in the intact coronary circulation.

Acetylcholine↗

PubMed2006

Discordant twin growth in utero and differences in blood pressure and endothelial function at 8 years of age.

OBJECTIVE: Low birth weight is associated with increased prevalence of hypertension and cardiovascular disease in adults. The aim of this study was to evaluate genetic and intrauterine environmental contributions to blood pressure (BP) and vascular functions in twins with discordant growth in utero. SUBJECTS: We studied 31 twin pairs (21 monozygous and nine dizygous), mean age 8 years) with large within-pair differences in birth weight. Among the monozygous pairs, nine had suffered from twin-to-twin-transfusion syndrome (TTTS). METHODS: Apart from BP, we determined diameters and elasticity of the carotid artery and abdominal aorta with ultrasonography, and endothelial function in skin vessels with a laser Doppler technique, before and after transdermal delivery of acetylcholine and nitroglycerin. RESULTS: Eight of 62 twin subjects had a systolic BP above the 90th percentile in a North-American reference population. Among these, seven/eight were monozygous with a history of poor fetal growth and/or TTTS. In monozygous twin pairs without TTTS, systolic BP and pulse pressure were higher and vascular endothelial function was impaired in the lower birth weight twin. In the TTTS group, the lighter twin had a narrower carotid artery but there was no within-pair difference in arterial elasticity. Pre-eclampsia during the index pregnancy enhanced within-pair differences in BP but abolished within-pair differences in endothelial function. CONCLUSIONS: Severe fetal growth retardation contributes to higher BP, arterial narrowing and endothelial dysfunction in childhood. Pre-eclampsia may act both as an effect modifier and confounder of these associations.

Acetylcholine↗

PubMed2003

Folate improves endothelial function in patients with coronary heart disease.

Elevated plasma homocysteine is associated with increased cardiovascular risk but it remains unproven that the effect is directly causal. Folate and homocysteine metabolism are closely linked such that administration of folic acid in doses ranging from 0.2-10 mg/day lowers plasma total homocysteine (tHcy) by up to 25%. Folic acid has been widely advocated as a therapy which may reduce cardiovascular risk, but the clinical benefit remains as yet unproven and the choice of dose remains unclear. The effect of folic acid on endothelial function has been investigated in patients with proven coronary heart disease (CHD) by measuring flow-mediated dilatation (FMD) in the brachial artery. Oral folic acid (5 mg/day) markedly enhances endothelial function (FMD) and lowers homocysteine. Studies of the acute effects of folic acid have shown that this improvement occurs within the first 2-4 hours following the first dose, at which times there was no significant reduction in plasma tHcy. Administration of 5-methyltetrahydrofolate directly into the brachial artery markedly enhances FMD, an effect that is blocked by monomethyl arginine (LNMMA), suggesting that the effects of folate are mediated by nitric oxide. This Review summarises studies which show that pharmacological doses of folate markedly enhance endothelial function in patients with CHD. The discordance with changes in plasma homocysteine suggests that these effects may occur by mechanisms distinct from homocysteine lowering.

Administration, Oral↗