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PubMed2003

Atherosclerotic involvement of the radial artery in patients with coronary artery disease and its relation with midterm radial artery graft patency and endothelial function.

BACKGROUND: The radial artery has recently been proposed as an alternative arterial conduit for surgical myocardial revascularization. This study was conceived to evaluate the degree of atherosclerotic involvement of the radial artery in patients with coronary artery disease and the eventual influence of a subtle degree of preoperative atherosclerosis on the midterm results of radial artery grafts. METHODS AND RESULTS: The intima-media thickness of the radial artery, common carotid artery, and internal thoracic artery was evaluated in 42 coronary artery disease patients and in 26 control patients. All radial arteries were then used for myocardial revascularization; 30 patients submitted to control angiography after 5 years. The mean intima-media thickness was 0.92 +/- 0.22 mm for the common carotid artery, 0.54 +/- 0.16 mm for the internal thoracic artery, 0.55 +/- 0.11 mm for the radial artery in coronary artery disease patients versus 0.79 +/- 0.14 mm, 0.52 +/- 0.11 mm, and 0.56 +/- 0.09 mm, respectively, in control patients (P =.001 only for the common carotid artery). No correlation was found between the intima-media thickness of the carotid, internal thoracic, and radial artery. No correlation was found between the preoperative intima-media thickness of the radial artery and the midterm patency and endothelial-mediated vasodilating capacity of radial artery grafts. CONCLUSION: In coronary artery disease patients, radial artery atherosclerotic involvement is more frequent than that of the gold standard internal thoracic artery but still by far less severe than that of the common carotid artery. The early atherosclerotic signs often observed in the radial artery do not seem to have the potential to influence radial artery graft patency and endothelial function.

Aged↗

PubMedDate not supplied

History of major depressive disorder and endothelial function in postmenopausal women.

OBJECTIVE: To determine whether history of depression is associated with endothelium-dependent flow-mediated dilation (FMD) in postmenopausal women. METHODS: Thirty-nine postmenopausal women with no known or suspected cardiovascular disease participated. Nineteen had a positive lifetime history of major depressive disorder, and 20 were never depressed. None were currently depressed, and all had been free of major depressive disorder and antidepressant medications for > or =1 year. History of depression was assessed with the Structured Clinical Interview for DSM-IV, enhanced by a modified version of the timeline follow-back method. Current depressive symptoms were measured with the Center for Epidemiological Studies Depression scale (CES-D). Brachial artery FMD was measured with ultrasound and calculated as percent dilation from baseline. RESULTS: After controlling for current subclinical depressive symptoms, ethnicity, hormone replacement therapy, and presence of the metabolic syndrome, previously depressed women showed significantly and clinically meaningful lower FMD than never depressed women. Controlling the same covariates, there was a dose-response relationship between number of depressive episodes and FMD. Examination of FMD means showed a significant negative correlation between number of depressive episodes and FMD. CONCLUSION: In postmenopausal women, depression continues to show a negative relationship to endothelial functioning even after years of remission. This relationship is not accounted for by residual depressive symptoms. Implications pertain to exclusion of previously depressed persons from control groups in research exploring the relationship between depression and cardiovascular disease.

Aged↗

PubMed1992

Intracoronary L-arginine during reperfusion improves endothelial function and reduces infarct size.

We tested the hypothesis that intracoronary administration of L-arginine (L-Arg), the physiological nitric oxide (NO) precursor, during reperfusion would attenuate postischemic damage by L-Arg NO-pathway mechanisms. Open-chest, anesthetized dogs underwent 60 min of left anterior descending coronary arterial (LAD) occlusion followed by 270 min of reperfusion. Dogs received intracoronary 10 mM L-Arg (n = 9 dogs), intracoronary 10 mM D-arginine (D-Arg, n = 7), or saline vehicle (Veh, n = 10) in the LAD during the first 120 min of reperfusion using an extracorporeal system. After 270 min of reperfusion, segmental systolic and diastolic function were comparably impaired in all three groups. Infarct size (triphenyltetrazolium chloride) expressed as a percentage of the area at risk (An/Ar) was significantly (P < 0.05) reduced in the L-Arg group (17.7 +/- 3.2%) compared with the Veh group (34.8 +/- 2.4%); D-Arg reversed this cardioprotection (48.8 +/- 5.2%, P < 0.05 vs. L-Arg, Veh). Cardiac myeloperoxidase activity, an index of neutrophil accumulation (U/100 mg tissue), was significantly (P < 0.05) lower in the necrotic tissue of the L-Arg group (0.88 +/- 0.26) than in the Veh group (2.46 +/- 0.38). Furthermore, responses to endothelium-dependent vasodilators acetylcholine and A23187 in isolated ischemic-reperfused LAD rings were significantly (P < 0.05) greater in the L-Arg group than in the other two groups. We conclude that intracoronary infusion of L-Arg during the early phase of reperfusion reduced neutrophil accumulation and infarct size and the infusion preserved endothelial function, possibly by increasing NO release or production by the endothelium.

Animals↗

PubMed2002

Population-based twin study of the effects of migration from Finland to Sweden on endothelial function and intima-media thickness.

Finnish men have higher coronary heart disease (CHD) mortality than Swedish men do. To assess the impact of migration to a country with lower CHD mortality on subclinical atherosclerosis, we measured early functional and structural atherosclerotic vascular changes in twins discordant for migration from Finland to Sweden. Conventional CHD risk factors, flow-mediated dilatation (FMD) of the brachial artery, carotid intima-media thickness, and carotid artery compliance were measured in 74 male twin pairs (20 monozygous, 54 dizygous), aged 42 to 69 years, in which co-one twin had migrated more than 20 years ago permanently to Sweden. There were no significant differences in CHD risk factors except for diastolic blood pressure and body fat percentage, which were higher in Sweden. In all subjects, mean FMD was non-significantly higher in Sweden (5.7+/-4.3% vs 4.9+/-4.2%, P=0.22), but in monozygous twins the difference in FMD was highly significant (7.2+/-4.4 vs 3.7+/-2.9%, P=0.003). There was no significant difference in intima-media thickness or carotid artery compliance between Sweden and Finland. We conclude that in Finnish monozygous twins the endothelial function is better among the twins that have migrated to a country with lower CHD prevalence.

Adult↗

PubMed2006

[Effect of therapy with rosuvastatin on lipid spectrum, factors of inflammation and endothelial function in patients with ischemic heart disease].

Rosuvastatin (10 mg) was given for 3 months to 30 men (mean age 57+/-9 years) with total cholesterol (CH) above 5.2 mmol/l. Questioning, physical examination, registration of ECG, measurement of levels of total, low density lipoprotein (LDL), high density lipoprotein (HDL) CH, and triglycerides (TG), assessment of endothelium-dependent brachial artery dilation were carried out at baseline and in 3 months. It was noted that 3 months therapy with rosuvastatin exerted positive effect on blood lipid spectrum: lowering of concentration of total CH (-31%, baseline 6.52+/-0.92, after therapy 4.47+/-0.96 mmol/l, p<0.0001), TG (-39%, baseline 2.73+/-1.56, after therapy 1.67+/-0.71 mmol/l, p<0.001), LDLCH (-44%, baseline 4.11+/-0.85, after therapy 2.40+/-0.90 mmol/l, p<0.0001), elevation of HDLCH (+6%, baseline 1.15+/-0.27, after therapy 1.22+/-0.34 mmol/l, p=0.08). Target LDL CH level (<2.6 mmol/l) was achieved in 23 patients (77%). Significant lowering of concentration of C-reactive protein (CRP) (-56%) and interleukin 6 (-25%) was also established. Before beginning of therapy mean flow dependent dilation was 6.1+/-1.64%, after therapy -- 10.4+/-5.0% (p<0.05). Treatment of men with ischemic heart disease with rosuvastatin (10 mg for 3 months) led to achievement of target values of LDLCH in 77% of them, to significant lowering of concentrations of CRP and interleukin 6, and to improvement of endothelial function.

Biomarkers↗

PubMed2004

Tamoxifen improves endothelial function and reduces carotid intima-media thickness in postmenopausal women.

BACKGROUND: Tamoxifen is a selective estrogen-receptor modulator shown to improve several cardiovascular risk factors in postmenopausal women with breast cancer. In animal studies tamoxifen inhibits the progression of atherosclerosis. Although the presence of a history with tamoxifen treatment is related to a lower intima-media thickness (IMT) of the common carotid artery, data from controlled follow-up studies are lacking to support this observation. METHODS: We examined 14 postmenopausal women with early stage breast cancer with indication for tamoxifen treatment (20 mg/d) and 13 healthy postmenopausal women. Flow-mediated dilatation (FMD) of the brachial artery, combined carotid IMT, and aortic pulse wave were measured before and 6 months after treatment in the tamoxifen group and at the same times in the control group. RESULTS: FMD and IMT were significantly increased and decreased, respectively, in the treatment group compared to the control group (FMD: +2.2% +/- 0.9% vs +0.085% +/- 1%, P =.012; IMT: -0.088 +/- 0.03 mm vs +0.04 +/- 0.03 mm, P =.018, mean +/- standard error of the mean, treatment vs control group). These differences remained significant even when adjusted for age, duration of menopause, and cardiovascular risk factors. Low-density lipoprotein cholesterol was also significantly reduced after tamoxifen treatment. CONCLUSIONS: Tamoxifen treatment slows the progression of atherosclerosis in postmenopausal women with breast cancer as assessed by changes in carotid IMT. An improvement in endothelial function and blood lipid profile may be the reason for this beneficial effect.

Aged↗

PubMed1988

Effects of oleic acid-, alpha-naphthylthiourea-, and phorbol myristate acetate-induced microvascular damage on indexes of pulmonary endothelial function in anesthetized dogs.

To study the value of indexes of endothelial cell function in experimentally induced pulmonary microvascular injury, lung damage was produced in anesthetized dogs by intravenous injection of oleic acid (OA; n = 6), alpha-naphthylthiourea (ANTU; n = 5), or phorbol myristate acetate (PMA; n = 6). Angiotensin-converting enzyme (ACE) activity in serum and simultaneous measurements of serotonin (SER) and propranolol (PROP) pulmonary extraction along with several physiologic parameters were determined and compared with those obtained in a control group (n = 5) before and then at 2-h intervals for 8 h after administration of the toxic agent. ACE activity in serum showed a sustained and significant increase in the PMA and OA groups throughout the whole study period, whereas it decreased significantly at 4 h in the ANTU group. SER pulmonary uptake decreased significantly, but slightly, only in the PMA group at 8 h (-5%). At 6 and 8 h respectively, PROP extraction dropped significantly in the PMA (-11 and -13%) and OA (-13 and -19%) groups. This decrease in PROP extraction was likely to result from physiologic changes due to the development of pulmonary edema as suggested by the correlation between the changes in amine uptake and those affecting pulmonary artery pressure and total static respiratory compliance. The lack of effects on SER uptake by the lungs under these experimental conditions indicate that dissociation exists between metabolic dysfunction of pulmonary endothelial cells and fluid leakage.

Anesthesia↗

PubMed1998

Losartan but not verapamil inhibits angiotensin II-induced tissue endothelin-1 increase: role of blood pressure and endothelial function.

Endothelin partially mediates angiotensin (Ang) II-induced vascular changes in vivo. This study investigated the effects of the angiotensin type 1 receptor antagonist losartan and the calcium channel blocker verapamil on vascular reactivity and tissue endothelin-1 levels in aortas of Wistar-Kyoto rats treated for 2 weeks with Ang II (200 ng x kg(-1) x min(-1)). Ang II increased systolic blood pressure (39+/-4 mm Hg, P<0.05). Concomitant treatment with losartan abolished the Ang II-induced pressure increase (P<0.05), whereas verapamil reduced it only partially (P<0.05). In the aortas of rats with Ang II-induced hypertension, tissue endothelin-1 content was increased threefold and contractions to endothelin-1 were impaired (P<0.05). Interestingly, these alterations were normalized by losartan (P<0.05) but not by verapamil. Hence, there was a strong, negative correlation between contractions to endothelin-1 and tissue endothelin-1 content (r=-0.733, P<0.0001). In contrast, both antihypertensive drugs normalized impaired endothelium-dependent relaxations to acetylcholine and reduced the sensitivity of vascular smooth muscle to sodium nitroprusside compared with Ang II-treated rats (P<0.05). Ang II-induced hypertension enhanced endothelium-dependent contractions to acetylcholine, and these were normalized by either drug. In conclusion, these findings suggest that long-term treatment with Ang II modulates endothelin-1 protein expression in the rat aorta. Although both antihypertensive agents lowered blood pressure and normalized endothelial function, only losartan prevented the increase in tissue endothelin-1 content, suggesting that angiotensin type 1 receptor antagonists but not calcium antagonists modulate tissue endothelin-1 in vivo.

Angiotensin II↗

PubMed2005

Hypoxia impairs systemic endothelial function in individuals prone to high-altitude pulmonary edema.

RATIONALE: High-altitude pulmonary edema (HAPE) is characterized by excessive pulmonary vasoconstriction and is associated with decreased concentrations of nitric oxide (NO) in the lung. OBJECTIVES: We hypothesized that individuals susceptible to HAPE (HAPE-S) would also have dysfunction of the vascular NO vasodilator pathway during hypoxia in the systemic vasculature. METHODS: During normoxia (FI(O(2)) = 0.21) and 4 hours of normobaric hypoxia (FI(O(2)) = 0.12, corresponding to an altitude of 4,500 m above sea level) endothelium-dependent and endothelium-independent vasodilator responses to intraarterial infusion of acetylcholine (ACh) and sodium nitroprusside, respectively, were measured by forearm venous occlusion plethysmography in nine HAPE-S subjects and in nine HAPE-resistant control subjects. MAIN RESULTS: Pulmonary artery systolic pressure increased from 22 +/- 3 to 33 +/- 6 mm Hg (p < 0.001) during hypoxia in control subjects, and from 25 +/- 4 to 50 +/- 9 mm Hg in HAPE-S subjects (p < 0.001). Despite similar responses during normoxia in both groups, ACh-induced changes in forearm blood flow markedly decreased during hypoxia in HAPE-S subjects (p = 0.01) but not in control subjects. The attenuated vascular response to ACh infusion during hypoxia inversely correlated with increased pulmonary artery systolic pressure (p = 0.04) and decreased plasma nitrite correlated with attenuated ACh-induced vasodilation in HAPE-S subjects (p = 0.02). CONCLUSIONS: Hypoxia markedly impairs vascular endothelial function in the systemic circulation in HAPE-S subjects due to a decreased bioavailability of NO. Impairment of the NO pathway could contribute to the enhanced hypoxic pulmonary vasoconstriction that is central to the pathogenesis of HAPE.

Acetylcholine↗

PubMed2006

Short-term statin treatment improves endothelial function and neurohormonal imbalance in normocholesterolaemic patients with non-ischaemic heart failure.

OBJECTIVES: To investigate the effect of short-term statin treatment on impaired endothelium-dependent vasodilatation and haemodynamic abnormalities typically occurring in chronic heart failure (CHF). METHODS: In a double-blind, crossover study endothelium-dependent vasodilatation was measured in conduit and resistance vessels of 23 patients with non-ischaemic CHF after 6 weeks of placebo and 40 mg atorvastatin. The haemodynamic impact was assessed by cardioendocrine hormones, echocardiography and clinical indicators of CHF. RESULTS: Cholesterol concentrations were population average (low density lipoprotein 3.56 (SEM 0.16) mmol/l, triglycerides 1.70 (0.20) mmol/l and high density lipoprotein 1.17 (0.07) mmol/l). In resistance vessels, the area under the curve ratio during acetylcholine infusion increased from 9.2 (1.9) with placebo to 12.2 (2.1) with statin (p < 0.01). This improvement was reversed during co-infusion with the nitric oxide antagonist N(G)-monomethyl-L-arginine. In conduit arteries, flow-mediated dilatation increased from 5.64 (SEM 0.88)% with placebo to 6.83 (0.97)% with statin (p < 0.05). Endothelium-independent vasodilatation did not change (p = 0.68 for conduit and p = 0.45 for resistance vessels). Endothelin 1 and atrial natriuretic peptide (ANP) decreased from 1.57 (0.08) and 51.3 (1.0) with placebo to 1.42 (0.09) pg/ml (p < 0.05) and 42.1 (7.5) pmol/l (p < 0.05), respectively, with statin. CONCLUSIONS: In patients with non-ischaemic CHF and population-average cholesterol concentrations, short-term statin treatment improves endothelial function in conduit and resistance vessels and lowers plasma endothelin 1 and ANP concentrations.

Atorvastatin↗

PubMed1994

The protective effect of L-arginine on myocardial injury and endothelial function following ischaemia and reperfusion in the pig.

The protective effect of the nitric oxide (NO) substrate L-arginine on myocardial ischaemial/reperfusion injury was studied in pigs. Four groups were subjected to 45 min ischaemia and 4 h reperfusion. One control group received coronary venous retroinfusion of saline, the second retroinfusion of L-arginine (1 mg.kg-1.min-1), the third retroinfusion of L-arginine plus the NO synthase inhibitor N omega-nitro-L-arginine (L-NNA), and the fourth systemic i.v. infusion of L-arginine (1 mg.kg-1.min-1). The infarct size in the L-arginine retroinfusion group was 35 +/- 5% of the myocardial area at risk compared to 76 +/- 5% in saline treated controls (P < 0.001). In pigs receiving the combination of retroinfused L-arginine and L-NNA the infarct size was similar to that of controls (79 +/- 4%). Systemic i.v. infusion of L-arginine did not influence the infarct size. Administration of L-NNA+L-arginine slightly increased arterial blood pressure during ischaemia but the groups did not differ in blood pressure, heart rate, rate-pressure product, left ventricular dP/dt or coronary blood flow during the reperfusion period. Coronary vasodilatation by acetylcholine was significantly compromised in the saline retroinfusion group, but not in the L-arginine retroinfusion group as compared to pigs not subjected to myocardial ischaemia. The results show that coronary venous retroinfusion of L-arginine reduces myocardial infarct size and preserves endothelial function via a local action which seems to be related to maintained nitric oxide formation.

Acetylcholine↗

PubMed1987

[Endothelial function and arteriosclerosis].

Elevated levels of plasma LDL have been correlated with morphological endothelial damages, e.g. reduced antithrombogenity of endothelial cells. Numerical and functional defects of endothelial cells probably influence the necessary separation of blood fractions from subendothelial tissues in a negative sense. In order to describe an imaginable endothelial dysfunction with respect to LDL transport we examined human umbilical venous endothelial cells (HUVEC) in culture under physiological flow conditions. HUVEC in culture after incubation with a LDL concentration of 100 micrograms/ml medium were exposed to defined levels of physiological shear stress, fixed with formalin and stained with oil-red-O. After documentation of oil-red-O staining with a photomicroscope, the amount of stain has been characterized semiquantitatively with the help of an image-analysis system (IBAS II/Zeiss). HUVEC not exposed to shear stress only showed a marginal oil-red-O staining at the cell surface. If they were exposed to shear stress of 0.5 dyn/cm2 they showed in orthogonal view an average increase of 1.3%, in cross-sectional view an average increase of 0.3%. HUVEC exposed to shear stress of 2.5 dyn/cm2 showed in orthogonal view an average increase of 4.6%, in cross-sectional view an average increase of 8.7%.

Arteriosclerosis↗

PubMed2001

Effects of low-dose aspirin on endothelial function in hypertensive patients.

BACKGROUND: It has been reported that administration of low-dose aspirin significantly reduces the frequency of major cardiovascular events in patients with hypertension and coronary artery disease. It is generally considered that the preventative effects of long-term aspirin administration on major cardiovascular events are due to the inhibition of platelet aggregation. HYPOTHESIS: It is not known whether administration of low-dose aspirin restores endothelium-dependent vasodilatation, and this study was undertaken to prove or disprove this question in patients with hypertension. METHODS: Flow-mediated endothelium-dependent dilatation and glyceryl trinitrate-induced endothelium-independent dilatation were investigated in 18 hypertensive patients and 10 normotensive control subjects. In the hypertensive patients, flow-mediated dilatation was investigated and cyclic guanosine monophosphate plasma (cGMP) was measured before and at 8 weeks after the administration of 162 mg of aspirin. RESULTS: Flow-mediated dilatation before aspirin administration was more reduced in the hypertensive patients than in the control subjects (6.4+/-2.0% vs. 11.3+/-2.3%, p <0.0001). Glyceryl trinitrate-induced dilatation before aspirin administration was similar in hypertensive patients and control subjects. Flow-mediated dilatation after aspirin administration was improved compared with that before aspirin administration (10.4+/-3.5% vs. 6.4+/-2.0%, p<0.0004). The cGMP product after aspirin administration was significantly higher than that before aspirin administration. CONCLUSIONS: Administration of low-dose aspirin may restore the endothelium-dependent vasodilatation in hypertensive patients. Furthermore, increased nitric oxide production may play a partial role in the improvement in endothelial function induced by administration of low-dose aspirin.

Aged↗

PubMed1987

Acute hypertension selectively potentiates constrictor responses of large coronary arteries to serotonin by altering endothelial function in vivo.

We tested the hypothesis that acute coronary artery hypertension may damage vascular endothelium and alter vasomotor responses to humoral agents. We examined effects of intracoronary infusion of the endothelium-dependent agent serotonin and two endothelium-independent agents, angiotensin II and methoxamine, on large coronary artery diameter in the blood perfused dog heart. Responses were examined before and 30 minutes after brief periods of coronary hypertension (200 mm Hg for 10 seconds to 15 minutes). In open-chest anesthetized dogs, the left anterior descending coronary artery was perfused at constant pressure. Coronary diameter (D) was measured with piezoelectric crystals. At a control perfusion pressure of 80 mm Hg, serotonin produced dose-dependent constriction of the large coronary artery (mean +/- SEM; delta D = -22 +/- 10 microns at 5 micrograms/min; -108 +/- 50 microns at 50 micrograms/min). Increasing perfusion pressure to 200 mm Hg increased flow 515 +/- 79% and coronary diameter 509 +/- 9 microns. After 15 minutes of hypertension, when coronary diameter had returned to baseline values, the constriction of the large artery to serotonin was potentiated (delta D = -89 +/- 33 microns at 5 micrograms/min; -207 +/- 45 microns at 50 micrograms/min; p less than 0.05). Hypertension for 1-5 minutes potentiated constrictor responses of large coronary arteries for at least 2 1/2 hours. Removal of endothelium prevented effects of hypertension on constrictor responses of large arteries to serotonin. Hypertension did not alter constrictor responses to angiotension II (1 and 2.5 micrograms/min) or methoxamine (50 and 100 micrograms/min) or the dilator response to acetylcholine (40 micrograms/min). Acute hypertension altered endothelial morphology. There were small endothelial craters following 10 seconds of hypertension, and disruption of endothelial junctions with leukocyte adherence following 1-15 minutes of hypertension. We conclude that acute hypertension alters constrictor responses of large coronary arteries to serotonin by impairing endothelial function and not by directly affecting vascular smooth muscle. These effects of acute hypertension on vascular reactivity are selective in that they do not involve non-endothelium-dependent agents or the endothelium-dependent agent, acetylcholine. The effect of hypertension also persists long after pressure is restored to normotensive levels.

Acetylcholine↗

PubMed1996

Physical fitness and endothelial function (nitric oxide synthesis) are independent determinants of insulin-stimulated blood flow in normal subjects.

Insulin induces vasodilation via stimulation of nitric oxide (NO) synthesis. This action of insulin exhibits considerable interindividual variation. We determined whether the response of blood flow to endothelium-dependent vasoactive agents correlates with that to insulin or whether other factors, such as physical fitness, limb muscularity, or vasodilatory capacity, better explain variations in insulin-stimulated blood flow. Direct measurements of the forearm blood flow response to three 2-h sequential doses of insulin (1, 2, and 5 mU/ kg.min), endothelium-dependent (acetylcholine and NG-monomethyl-L-arginine) and endothelium-independent (sodium nitroprusside) vasoactive agents, and ischemia (reactive hyperemic forearm blood flow) were performed in 22 normal subjects (age, 24 +/- 1 yr; body mass index, 22.2 +/- 0.6 kg/m2; maximal aerobic power, 40 +/- 2 mL/kg.min). The highest insulin dose increased blood flow by 111 +/- 17%. The fraction of basal blood flow inhibited by NG-monomethyl-L-arginine (NO synthesis-dependent flow) varied from 6-47%. Maximal aerobic power (r = 0.52; P < 0.02), the percentage of forearm muscle (r = 0.50; P < 0.02), and the NO synthesis-dependent flow (r = 0.42; P < 0.05), but not reactive hyperemic, acetylcholine-stimulated, or sodium nitroprusside-stimulated flow, were significantly correlated with insulin-stimulated (5 mU/kg.min) blood flow. In multiple linear regression analysis, 52% of the variation (multiple R = 0.72; P < 0.001) in insulin-stimulated blood flow was explained by NO synthesis-dependent flow (P < 0.005) and the percentage of forearm muscle (P < 0.005). We conclude that endothelial function (NO synthesis-dependent basal blood flow) and forearm muscularity are independent determinants of insulin-stimulated blood flow.

Adult↗

PubMed1997

Dietary supplementation with marine fish oil improves in vitro small artery endothelial function in hypercholesterolemic patients: a double-blind placebo-controlled study.

BACKGROUND: Marine fish oils improve vascular function, but the mechanism of benefit is unclear. We conducted a study to examine the effects of fish oils given to hypercholesterolemic patients on small artery function in vitro. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled trial, subcutaneous gluteal fat biopsies were taken from 16 hypercholesterolemic patients (serum total cholesterol, 7.97+/-0.16 mmol/L [mean+/-SEM]) and 12 age- and sex-matched control subjects (mean cholesterol, 5.11+/-0.34 mmol/L). Small arteries were mounted on a wire myograph for isometric tension experiments. Patients and control subjects were randomized to receive fish oil (Maxepa 5 capsules BID) or placebo for 3 months. A second biopsy was taken and the studies were repeated. Relaxation to acetylcholine was significantly improved in the hypercholesterolemic group given Maxepa but not in the placebo group (mean maximum relaxation before and after, 48+/-6.2% and 68.83+/-2.19%, P=.0054). The dysfunction was not restored to control values (84.3+/-5.2%, P=.0002). There was also a smaller but significant impairment in endothelium-independent relaxation provoked by sodium nitroprusside (P<.01). A good correlation between the increase in eicosapentanoic acid (n=3) in red cell membrane and improvement in relaxation in the hypercholesterolemic group given fish oils was seen (r=.781, P<.02). CONCLUSIONS: Marine fish oil significantly improved endothelial function in peripheral small arteries in hypercholesterolemia patients. This may provide a mechanism for the beneficial effects of these fatty acids in coronary heart disease.

Adult↗

PubMed2004

Electrophysiologic and mechanical evidence of superiority of hyperpolarizing versus depolarizing cardioplegia in protection of endothelium-derived hyperpolarizing factor-mediated endothelial function: a study in coronary resistance arteries.

OBJECTIVE: The advantages of hyperpolarizing cardioplegia with potassium-channel openers versus depolarizing cardioplegia have been suggested but not demonstrated in coronary microarteries. This study examined the simultaneous electric and tonic alteration of coronary microarteries at the cellular level during and after exposure to depolarizing cardioplegia or hyperpolarizing cardioplegia, with emphasis on endothelium-derived hyperpolarizing factor-mediated relaxation and hyperpolarization. METHODS: Porcine coronary microarteries (diameter, approximately 200-400 microm) were incubated with depolarizing cardioplegia (20 mmol/L KCl) or hyperpolarizing cardioplegia (10 micromol/L aprikalim) for 1 hour. Cellular membrane potential with a glass microelectrode in a coronary smooth muscle cell and isometric force of the muscle were simultaneously measured in a myograph. RESULTS: Depolarizing cardioplegia incubation produced a stable contraction (from 4.9 +/- 0.3 mN to 7.3 +/- 0.4 mN) and depolarization (from -51 +/- 1 mV to -41 +/- 2 mV). In contrast, hyperpolarizing cardioplegia relaxed (from 4.8 +/- 0.3 mN to 3.5 +/- 0.3 mN) and hyperpolarized (from -51 +/- 2 mV to -56 +/- 1 mV) the smooth muscle. After exposure to depolarizing cardioplegia, the bradykinin-induced, endothelium-derived hyperpolarizing factor-mediated relaxation reduced from 66.2% +/- 5.0% to 18.4% +/- 3.7% (P <.001), and the membrane hyperpolarization reduced from 18 +/- 1 mV to 7 +/- 1 mV (P <.001) in the presence of indomethacin and N(G)-nitro-L-arginine. In contrast, hyperpolarizing cardioplegia did not affect the bradykinin-induced responses. CONCLUSIONS: In the coronary microarteries, exposure to hyperpolarizing cardioplegia preserves whereas depolarizing cardioplegia reduces the endothelium-derived hyperpolarizing factor-mediated electric (hyperpolarization) and mechanical (relaxation) responses. Thus hyperpolarizing cardioplegia is superior to depolarizing cardioplegia in protecting the endothelial function in the coronary microcirculation.

Animals↗

PubMed2003

Effects of hypochlorite and hydrogen peroxide on cardiac autonomic receptors and vascular endothelial function.

1. Reactive oxygen species (ROS) are known to be involved in the progression of various cardiovascular diseases. One source of ROS is activated neutrophils, which can release superoxide anion radicals and hydrogen peroxide by membrane-bound NAD(P)H oxidases. These ROS not only destroy bacteria, but may also affect mammalian tissue. In addition, hydrogen peroxide serves as a substrate for myeloperoxidase, an enzyme that is released by activated neutrophils during inflammatory processes, as seen, for instance, in reperfusion injury and atherosclerosis. Myeloperoxidase catalyses the oxidation of chloride by hydrogen peroxide, yielding hypochlorite, an extremely potent oxidant. 2. The purpose of the present study was to evaluate the effects of hypochlorite on a variety of receptor-dependent processes in rat isolated left atria and rat thoracic aorta and to compare these results with the phenomena observed after incubation with hydrogen peroxide. 3. In the presence of hypochlorite (300 micro mol/L), the positive inotropic response of alpha1-adrenoceptor stimulation by methoxamine (300 micro mol/L) was converted into a negative inotropic response. In contrast, the positive inotropic effects of the beta1/beta2-adrenoceptor agonist isoprenaline (3 micro mol/L) and endothelin (ET)-1 (100 nmol/L) remained largely unaffected. 4. The inversion of alpha1-adrenoceptor-mediated inotropy was not obtained in the presence of hydrogen peroxide (500 micro mol/L). Hydrogen peroxide did not affect the positive inotropic response of isoprenaline, but it completely abolished the inotropic effect of ET-1. 5. The effect of cardiac M2-receptor stimulation was studied in the presence of hypochlorite and hydrogen peroxide. The negative inotropic response to acetylcholine (ACh) was significantly enhanced after hypochlorite incubation compared with control. 6. In the rat thoracic aorta, endothelial function, evaluated by means of ACh-induced vasodilation, was completely abolished in the presence of hypochlorite (100 micro mol/L), but remained unaffected by treatment with the same concentration of hydrogen peroxide. 7. From these data, we conclude that hypochlorite exerts more toxic properties than its precursor hydrogen peroxide, leading to substantial physiological alterations in cardiac and vascular tissue.

Acetylcholine↗