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Biomedical subjects

G Noll

Publications and source records attributed to G Noll.

At least 19 recordsLinked to original sources
PubMed2005

[Coffee--poison or medicine?].

Intake of coffee, one of the most common beverages worldwide, has often been discussed as a potential cardiovascular risk factor. However, definitive data about this topic are missing and newer studies even point out for a favorable rather than hazardous effect. Despite many studies no clear association between coffee and the risk of hypertension, myocardial infarction and other cardiovascular diseases was found. Recent publications suggest that moderate coffee intake does not represent a health hazard, but may even be associated with beneficial effects on the cardiovascular system and diabetes.

Cardiovascular Diseases↗
PubMed2005

[The sweet secret of dark chocolate].

For centuries dark chocolate has been known for its taste as well as its beneficial effects on health. Mainly polyphenols, a heterogeneous group of molecules, have been associated with antioxidant and immunomodulatory properties. Furthermore they inhibit primary hemostasis and pathways associated with platelet activation and aggregation.

Administration, Oral↗
PubMed2003

[Pathophysiologic cardiovascular changes in stress and depression].

Fear, anger, and grief may precipitate myocardial ischemia and infarction. The prognosis of patients with inducible ischemia during mental stress is worse than in those without inducible ischemia. The sympathetic nervous system plays an important role in stress-associated changes in cardiovascular regulation and contributes to cardiovascular morbidity and mortality by inducing vasoconstriction and tachycardia, as well as arrhythmia. Hostility--previously termed type A personality--is often associated with sympathetic hyperreactivity to mental stress and carries an increased risk for atherosclerotic vascular disease. As endothelial dysfunction is an early manifestation of atherosclerosis, the impact of mental stress on endothelial function is also important. Acute mental stress induces prolonged endothelial dysfunction in healthy volunteers, which is prevented by selective endothelin A receptor antagonism. This represents an important link between mental stress and atherosclerotic vascular disease. In addition, patients with depression show hypercortisolemia, and changes in platelet function leading to a prothrombotic state. These findings help to explain the increased cardiovascular risk in patients with depression.

Arousal↗
PubMed2001

Stent coating with titanium-nitride-oxide for reduction of neointimal hyperplasia.

BACKGROUND: Coronary stents prevent constrictive arterial remodeling but stimulate neointimal hyperplasia. Stainless steel induces a metallic foreign body reaction, which is absent for titanium. The hypothesis of the present study was that titanium renders the stent surface biologically inert, with reduced platelet and fibrinogen binding. METHODS AND RESULTS: Twelve pigs were instrumented with a stainless steel and 2 titanium-nitride-oxide-coated stents (TiNOX 1, ceramic; TiNOX 2, metallic). Animals were restudied after 6 weeks. Histological specimens of stented segments were analyzed by digital morphometry. Platelet adhesion and fibrinogen binding studies were performed in the perfusion chamber. Under in vitro conditions, TiNOX 1 showed reduced platelet adhesion (65+/-3%) compared with TiNOX 2 (72+/-5%; P<0.05) and stainless steel (71+/-4%; P<0.05). Platelet adhesion 48 hours after incubation with human plasma, however, was not different between TiNOX 1 (17+/-3%) and 2 (15+/-3%) but was significantly higher with stainless steel (23+/-2%; P<0.05). Fibrinogen binding was significantly reduced with TiNOX 2 (54+/-3%) compared with TiNOX 1 (82+/-4%, P<0.05) or stainless steel (100%, P<0.05). Histomorphometry revealed a significantly larger neointimal area in stainless steel (2.61+/-1.12 mm(2)) than in TiNOX 1-coated (1.47+/-0.84 mm(2), P<0.02) or TiNOX 2-coated (1.39+/-0.93 mm(2), P<0.02) stents. The reductions were 44% and 47%, respectively. CONCLUSIONS: TiNOX coating significantly reduces neointimal hyperplasia in stainless steel stents. The antiproliferative effect was similar for both TiNOX coatings, suggesting that the electrochemical properties are more important for attenuation of neointimal proliferation than the observed differences in platelet adhesion and fibrinogen binding.

Alloys↗
PubMed2001

Endothelin 1 type a receptor antagonism prevents vascular dysfunction and hypertension induced by 11beta-hydroxysteroid dehydrogenase inhibition: role of nitric oxide.

BACKGROUND: The enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) prevents inappropriate activation of the nonselective mineralocorticoid receptors by glucocorticoids. Renal activity of 11beta-HSD is decreased in patients with apparent mineralocorticoid excess (SAME), licorice-induced hypertension, and essential hypertension. Although expressed in vascular cells, the role of 11beta-HSD in the regulation of vascular tone remains to be determined. METHODS AND RESULTS: lycyrrhizic acid (GA; 50 mg/kg IP, twice daily for 7 days) caused a significant inhibition of 11beta-HSD activity and induced hypertension in Wistar-Kyoto rats (157 versus 127 mm Hg in controls; P<0.01). After 11beta-HSD inhibition, aortic endothelial nitric oxide (NO) synthase (eNOS) protein content, nitrate tissue levels, and acetylcholine-induced release of NO were blunted (all P<0.05 versus controls). In contrast, vascular prepro-endothelin (ET)-1 gene expression, ET-1 protein levels, and vascular reactivity to ET-1 were enhanced by GA treatment (P<0.05 versus controls). Chronic ET(A) receptor blockade with LU135252 (50 mg. kg(-1). d(-1)) normalized blood pressure, ET-1 tissue content, vascular reactivity to ET-1, vascular eNOS protein content, and nitrate tissue levels and improved NO-mediated endothelial function in GA-treated rats (P<0.05 to 0.01 versus untreated and verapamil-treated controls). In human endothelial cells, GA increased production of ET-1 in the presence of corticosterone, which indicates that activation of the vascular ET-1 system by 11beta-HSD inhibition can occur independently of changes in blood pressure but is dependent on the presence of glucocorticoids. CONCLUSIONS: Chronic ET(A) receptor blockade normalizes blood pressure, prevents upregulation of vascular ET-1, and improves endothelial dysfunction in 11beta-HSD inhibitor-induced hypertension and may emerge as a novel therapeutic approach in cardiovascular disease associated with reduced 11beta-HSD activity.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2001

Endothelin receptor antagonists in congestive heart failure: a new therapeutic principle for the future?

Congestive heart failure (CHF) is characterized by impaired left ventricular function, increased peripheral and pulmonary vascular resistance and reduced exercise tolerance and dyspnea. Thus, mediators involved in the control of myocardial function and vascular tone may be involved in its pathophysiology. The family of endothelins (ET) consists of four closely related peptides, ET-1, ET-2, ET-3 and ET-4, which cause vasoconstriction, cell proliferation and myocardial effects through activation of ETA receptors. In contrast, endothelial ETB receptors mediate vasodilation via release of nitric oxide and prostacyclin. In addition, ETB receptors in the lung are a major pathway for the clearance of ET-1 from plasma. Thus, infusion of an ETA-receptor antagonist into the brachial artery in healthy humans leads to vasodilation, whereas infusion of an ETB-receptor antagonist causes vasoconstriction. Endothelin-1 plasma levels are elevated in CHF and correlate both with hemodynamic severity and symptoms. Plasma levels of ET-1 and its precursor, big ET-1, are strong independent predictors of death after myocardial infarction as well as in CHF. Endothelin-1 contributes to increased systemic and pulmonary vascular resistance, vascular dysfunction, myocardial ischemia and renal impairment in CHF. Selective ETA, as well as combined ETA/B-receptor antagonists, have been studied in patients with CHF, and their use has shown impressive hemodynamic improvement (i.e., reduced peripheral vascular and pulmonary resistance as well as increased cardiac output). These results indicate that ET-receptor antagonists, indeed, have a potential to improve hemodynamics, symptoms and, potentially, prognosis in patients with CHF, which still carries a high mortality.

Antihypertensive Agents↗
PubMed2001

Endothelin A receptor antagonists in congestive heart failure: blocking the beast while leaving the beauty untouched?

Congestive heart failure (CHF) is a disease process characterized by impaired left ventricular function, increased peripheral and pulmonary vascular resistance and reduced exercise tolerance and dyspnea. Thus, mediators involved in the control of myocardial function and vascular tone may be involved in its pathophysiology. The family of endothelins (ET) consists of four closely related peptides, ET-1, ET-2, ET-3, and ET-4, which cause vasoconstriction, cell proliferation, and myocardial effects through activation of ET(A) receptors. In contrast, endothelial ET(B) receptors mediate vasodilation via release of nitric oxide and prostacyclin. In addition, ET(B) receptors in the lung are a major pathway for the clearance of ET-1 from plasma. Thus, infusion of an ET(A) receptor antagonist into the brachial artery in healthy humans leads to vasodilation whereas infusion of an ET(B) receptor antagonist causes vasoconstriction. ET-1 plasma levels are elevated in CHF and correlate both with the hemodynamic severity and with symptoms. Plasma levels of ET-1 and its precursor, big ET-1, are strong independent predictors of death in patients after myocardial infarction and with CHF. ET-1 contributes to increased systemic and pulmonary vascular resistance, vascular dysfunction, myocardial ischemia, and renal impairment in CHF. Selective ET(A) as well as combined ET(A/B) receptor antagonists have been studied in patients with CHF showing impressive hemodynamic improvements (i.e. reduced peripheral vascular and pulmonary resistance as well as increased cardiac output). These results indicate that ET receptor antagonists indeed have a potential to improve hemodynamics, symptoms, and potentially prognosis of CHF which still carries a high mortality.

Coronary Circulation↗
PubMed2001

Cycle length-associated modulation of the regional dispersion of ventricular repolarization in a canine model of long QT syndrome.

Previous tridimensional activation mapping showed that the development of functional conduction block at the onset of torsades de pointes was regionally heterogeneous; conduction block was frequently observed in the LV and the interventricular septum (IVS) but not in the RV, in the canine anthopleurin-A (AP-A) model of long QT syndrome (LQTS). This may be related to the distribution of myocytes with M celllike electrophysiological characteristics. To better understand the regional difference of arrhythmogenicity in LQTS, the authors investigated cycle length related modulation of ventricular repolarization among three different layers: the endocardium (End), mid-myocardium (Mid), and epicardium (Epi) of the LV and RV and at two different areas: the Epi and septum (Sep) in the IVS. The LQT3 model was produced by AP-A in dogs. Using constant pacing and single premature stimulation (S1S2), the ventricular repolarization pattern was analyzed from 256 unipolar electrograms. Activation-recovery intervals (ARIs) were used to estimate local repolarization. In seven experiments, AP-A increased regional ARI dispersion to 88.1 +/- 36.0 ms in the LV, to 72.9 +/- 35.7 ms in the IVS, and to 23.0 +/- 8.7 ms in the RV at the pacing cycle length (CL) of 1,000 ms. Development of the large ARI dispersion was due to greater ARI prolongation at the Mid site in the LV and at Sep site in the IVS. As the S1S2 interval was shortened, regional ARI dispersion decreased gradually, and finally, ARI dispersion showed a reversal gradient of repolarization between the Mid and Epi sites in the LV and between the Sep and Epi sites in the IVS. Two factors contributed to create the reversal gradient of repolarization: (1) a difference in restitution kinetics at the Mid site in the LV and at the Sep site in the IVS, characterized by a larger delta ARI and slower time constant (tau), and (2) a difference in diastolic intervals at each site resulting in different input to restitution at the same CL. However, the RV showed small alteration in the transmural dispersion of repolarization in the S1S2 protocol. S2 created heterogeneous functional conduction block in the LV and IVS but not in the RV. In the LQT3 model, the arrhythmogenicity of torsades de pointes is primarily due to dispersion of repolarization in the LV and IVS because of prominent distribution of M cells. The RV seems to participate passively in reentrant excitation during torsades de pointes.

Animals↗
PubMed2001

Current strategies and perspectives for correcting endothelial dysfunction in atherosclerosis.

The vascular endothelium synthesizes and releases a spectrum of vasoactive substances such as nitric oxide and endothelin. In atherosclerosis, the delicate balance between endothelium-derived factors is disturbed. Endothelin acts as the natural counterpart to endothelium-derived nitric oxide, which exerts vasodilating, antithrombotic and antiproliferative effects, and inhibits leukocyte adhesion to the vascular wall. Besides its blood pressure increasing effect in man, endothelin also induces vascular and myocardial hypertrophy, which are independent risk factors for cardiovascular morbidity and mortality. The derangement of endothelial function in atherosclerosis is likely to be caused in part by genetic factors, but is also due to cardiovascular risk factors. Endothelial dysfunction in atherosclerosis is crucial for the development of the disease process in the vasculature and is therefore an important therapeutic target. However, the efficacy of pharmacotherapy aimed at an improvement in endothelial function depends on the individual risk factor profile of the patient.

Adrenergic beta-Antagonists↗
PubMed2001

Vascular effects of newer cardiovascular drugs: focus on nebivolol and ACE-inhibitors.

Alterations in the function and structure of the blood vessel wall account for most clinical events in the coronary and cerebrovascular circulation such as myocardial infarction and stroke. Cardiovascular drugs may exert beneficial effects on the vascular wall both at the level of the endothelium and vascular smooth muscle cells. Therefore, endothelial mediators, in particular nitric oxide (NO) and endothelin (ET), are of special interest. Drugs can modulate the expression and actions of NO, a vasodilator with antiproliferative and antithrombotic properties, and of ET, a potent vasoconstrictor and proliferative mitogenic agent. The most successful drugs in this context are statins and angiotensin-converting enzyme (ACE)-inhibitors. While statins increase the expression of NO synthase. ACE-inhibitors increase the release of NO via bradykinin-mediated mechanisms. Antioxidant properties of drugs are also important, as oxidative stress is crucial in atherosclerotic vascular disease. These properties may explain part of the effects of calcium antagonists and ACE-inhibitors. Indeed, angiotensin II stimulates NAD(P)H oxidases responsible for the formation of superoxide, which inactivates NO. ACE-Inhibitors thus increase the bioavailability of NO. Newer cardiovascular drugs such as nebivolol are able to directly stimulate NO release from the endothelium both in isolated arteries and in the human forearm circulation. ET receptor antagonists may exert beneficial effects in the vessel wall by preventing the effects of ET at its receptors and by reducing ET production. In summary, cardiovascular drugs have important effects on the vessel wall, which may be clinically relevant for the prevention and treatment of cardiovascular disease.

Adrenergic beta-1 Receptor Antagonists↗
PubMed2001

Therapeutic potential for endothelin receptor antagonists in cardiovascular disorders.

The endothelins are synthesized in vascular endothelial and smooth muscle cells, as well as in neural, renal, pulmonal, and inflammatory cells. These peptides are converted by endothelin-converting enzymes (ECE-1 and -2) from 'big endothelins' originating from large preproendothelin peptides cleaved by endopeptidases. Endothelin (ET)-1 has major influence on the function and structure of the vasculature as it favors vasoconstriction and cell proliferation through activation of specific ET(A) and ET(B) receptors on vascular smooth muscle cells. In contrast, ET(B )receptors on endothelial cells cause vasodilation via release of nitric oxide (NO) and prostacyclin. Additionally, ET(B) receptors in the lung are a major pathway for the clearance of ET-1 from plasma. Indeed, ET-1 contributes to the pathogenesis of important disorders as arterial hypertension, atherosclerosis, and heart failure. In patients with atherosclerotic vascular disease (as well as in many other disease states), ET-1 levels are elevated and correlate with the number of involved sites. In patients with acute myocardial infarction, they correlate with 1-year prognosis. ET receptor antagonists have been widely studied in experimental models of cardiovascular disease. In arterial hypertension, they prevent vascular and myocardial hypertrophy. Experimentally, ET receptor blockade also prevents endothelial dysfunction and structural vascular changes in atherosclerosis due to hypercholesterolemia. In experimental myocardial ischemia, treatment with an ET receptor antagonist reduced infarct size and prevented left ventricular remodeling after myocardial infarction. Most impressively, treatment with the selective ET(A) receptor antagonist BQ123 significantly improved survival in an experimental model of heart failure. In many clinical conditions, such as congestive heart failure, both mixed ET(A/B )as well as selective ET(A) receptor antagonism ameliorates the clinical status of patients, i.e. symptoms and hemodynamics. A randomized clinical trial showed that a mixed ET(A/B) receptor antagonist effectively lowered arterial blood pressure in patients with arterial hypertension. In patients with primary pulmonary hypertension or pulmonary hypertension related to scleroderma, treatment with a mixed ET(A/B) receptor antagonist resulted in an improvement in exercise capacity. ET receptor blockers thus hold the potential to improve the outcome in patients with various cardiovascular disorders. Randomized clinical trials are under way to evaluate the effects of ET receptor antagonism on morbidity and mortality.

Animals↗
PubMed2000

Nitric oxide prevents cardiovascular disease and determines survival in polyglobulic mice overexpressing erythropoietin.

Nitric oxide (NO) induces vasodilatatory, antiaggregatory, and antiproliferative effects in vitro. To delineate potential beneficial effects of NO in preventing vascular disease in vivo, we generated transgenic mice overexpressing human erythropoietin. These animals induce polyglobulia known to be associated with a high incidence of vascular disease. Despite hematocrit levels of 80%, adult transgenic mice did not develop hypertension or thromboembolism. Endothelial NO synthase levels, NO-mediated endothelium-dependent relaxation and circulating and vascular tissue NO levels were markedly increased. Administration of the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) led to vasoconstriction of peripheral resistance vessels, hypertension, and death of transgenic mice, whereas wild-type siblings developed hypertension but did not show increased mortality. L-NAME-treated polyglobulic mice revealed acute left ventricular dilatation and vascular engorgement associated with pulmonary congestion and hemorrhage. In conclusion, we here unequivocally demonstrate that endothelial NO maintains normotension, prevents cardiovascular dysfunction, and critically determines survival in vivo under conditions of increased hematocrit.

Animals↗
PubMed2000

Tissue endothelin-converting enzyme activity correlates with cardiovascular risk factors in coronary artery disease.

BACKGROUND: Endothelin-converting enzymes (ECEs) are the key enzymes in endothelin-1 (ET-1) generation. However, their pathophysiological role in patients with cardiovascular disease remains elusive. METHODS AND RESULTS: Vascular reactivity to big endothelin-1 (bigET-1; 10(-9) to 10(-7) mol/L) and ET-1 (10(-9) to 10(-7) mol/L) were examined in the internal mammary artery (IMA, n=33) and saphenous vein (SV, n=27) of patients with coronary artery disease with identified cardiovascular risk factors. Vascular ECE activity was determined by conversion of exogenously added bigET-1 to ET-1. Tissue contents of bigET-1 and ET-1 were measured by radioimmunoassay. In addition, the effects of LDL and oxidized LDL on ECE-1 protein levels were determined by Western blot analysis in human IMA endothelial cells. In the IMA, vascular ECE activity showed an inverse correlation with serum LDL levels (r=-0.76; P<0.01) and systolic and diastolic blood pressure and a positive correlation with fibrinogen (r=0.58; P<0.05). In the SV, fibrinogen was the only parameter to be correlated with vascular ECE activity. Vascular tissue content of bigET-1 was attenuated in the IMA of patients with hyperfibrinogenemia but increased in patients with elevated systolic blood pressure and increased serum LDL levels (P<0.05). Most interestingly, LDL and oxidized LDL downregulated ECE-1 protein levels in human IMA endothelial cells (P<0.05). CONCLUSIONS: These data demonstrate, for the first time, that vascular ECE activity is (1) inversely correlated with serum LDL levels and blood pressure and (2) positively associated with fibrinogen in human vascular tissue. Hence, ECE-1 activity may modulate cardiovascular risk in patients with coronary artery disease.

Aspartic Acid Endopeptidases↗