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Biomedical subjects

G Noll

Publications and source records attributed to G Noll.

At least 73 records · Page 4Linked to original sources
PubMed1997

Synchronous and baroceptor-sensitive oscillations in skin microcirculation: evidence for central autonomic control.

To determine whether skin blood flow is local or takes part in general regulatory mechanisms, we recorded laser-Doppler flowmetry (LDF; left and right index fingers), blood pressure, muscle sympathetic nerve activity (MSNA), R-R interval, and respiration in 10 healthy volunteers and 3 subjects after sympathectomy. We evaluated 1) the synchronism of LDF fluctuations in two index fingers, 2) the relationship with autonomically mediated fluctuations in other signals, and 3) the LDF ability to respond to arterial baroreflex stimulation (by neck suction at frequencies from 0.02 to 0.20 Hz), using spectral analysis (autoregressive uni- and bivariate, time-variant algorithms). Synchronous LDF fluctuations were observed in the index fingers of healthy subjects but not in sympathectomized patients. LDF fluctuations were coherent with those obtained for blood pressure, MSNA, and R-R interval. LDF fluctuations were leading blood pressure in the low-frequency (LF; 0.1 Hz) band and lagging in the respiratory, high-frequency (HF; approximately 0.25 Hz) band, suggesting passive "downstream" transmission only for HF and "upstream" transmission for LF from the microvessels. LDF fluctuations were responsive to sinusoidal neck suction up to 0.1 Hz, indicating response to sympathetic modulation. Skin blood flow thus reflects modifications determined by autonomic activity, detectable by frequency analysis of spontaneous fluctuations.

Adult↗
PubMed1997

The endothelium in coronary artery disease.

An increasing body of evidence indicates that the endothelium is crucially involved in the regulation of coronary blood flow and cardiac function. Injury to the endothelium precipitates atherosclerosis by leading to smooth-muscle-cell migration and proliferation, induction of expression of growth factors and impairment in the plasmatic coagulation and endogenous fibrinolysis system. Strategically located between the circulating blood and the vascular smooth muscle, endothelial cells release numerous vasoactive substances regulating the function of vascular smooth muscle and trafficking blood cells. Important endothelium-derived vasodilators are prostacyclin, bradykinin, nitric oxide and, independent of the former, endothelium-derived hyperpolarizing factor. In particular, nitric oxide inhibits cellular growth and migration. In concert with prostacyclin, nitric oxide exerts potent antiatherogenic and thromboresistant properties by preventing platelet aggregation and cell adhesion. These effects are counterbalanced by endothelial vasoconstrictors, such as angiotensin II and endothelin-1, both of which exert prothrombotic and growth-promoting properties. Modern therapeutic strategies in coronary artery disease focus on preserving or restoring endothelial integrity. Whereas nitrates partly substitute deficient endogenous nitric oxide, calcium antagonists counteract angiotensin II and endothelin-1 at the level of vascular smooth muscle by reducing Ca2+ inflow and facilitating the vasodilator effects of nitric oxide. Beyond inhibiting the renin-angiotensin system, angiotensin-converting enzyme inhibitors diminish the inactivation of bradykinin, thus leading to an augmentation of nitric oxide release. Furthermore, newly developed specific endothelin antagonists will provide us with greater insight into the beneficial effects of restoring endothelial dysfunction in cardiovascular disease. Thus, drugs can directly affect endothelial function, prevent the action of endothelial mediators, substitute for deficient endothelial factors or indirectly exert protective effects by interfering with cardiovascular risk factors.

Animals↗
PubMed1997

Endothelium and high blood pressure.

Due to its strategic anatomical position, the endothelium is constantly exposed to the different risk factors for atherosclerosis. During the last decade it has become clear that hypertension profoundly affects endothelial function. Depending on the form of hypertension, endothelium-dependent relaxation is impaired in most vascular beds. In spontaneous hypertension, the production of nitric oxide, which in endothelial cells is formed from L-arginine via the constitutively expressed enzyme endothelial nitric oxide synthase, represents the main mediator of endothelium-dependent vasodilation and seems to be enhanced. On the other hand, the release of endothelium-dependent contracting factors such as prostaglandin H2 and thromboxane A2 have been demonstrated in this model of hypertension. Similar results have been obtained in the forearm circulation of patients with essential hypertension. In contrast, in models of salt-sensitive hypertension no release of vasoconstrictor prostanoids can be found indicating a decreased production of nitric oxide. Thus, in spontaneous hypertension an increased production of nitric oxide seems to occur, which is ineffective due to either the simultaneous release of endothelium-dependent vasoconstrictors and/or inactivation of nitric oxide, or due to anatomical changes such as hypertension-induced intimal thickness which inhibits its action on vascular smooth muscle cells. In summary, in hypertension, endothelium-dependent vasodilation is blunted and the endothelial L-arginine nitric oxide pathway is altered. These changes seem to represent a consequence rather than a cause of hypertension.

Animals↗
PubMed1996

[Heart, brain and hypertension].

Hypertension is one of the most important cardiovascular risk factors. Without therapy hypertension leads to stroke, coronary heart disease with angina pectoris and myocardial infarction, kidney failure and/or peripheral vascular disease. The association between blood pressure and these cardiovascular complications can be demonstrated over the entire blood pressure range. The risk of stroke, myocardial infarction, renal failure or peripheral vascular disease increases with increasing blood pressure. Additional cardiovascular risk factors such as hyperlipidemia, smoking and diabetes involve a further increase in risk. Today hypertension can be effectively treated. To that end, diuretics, betablockers, ACE-inhibitors or calcium antagonists can be used. Alpha receptor antagonists and angiotensin AT1 receptor antagonists are also of value. The antihypertensive effectiveness of these drugs is comparable but may vary in individual patients. During antihypertensive therapy, a reduction in cerebrovascular and cardiac complications has been demonstrated for alpha methyldopa, diuretics and betablockers. In these studies, fatal and non-fatal strokes were reduced by 42%, while the reduction in cardiac events was less pronounced (14%). The reasons for this greater efficacy of antihypertensive therapy in the cerebral circulation are not clear. Other risk factors may be particularly important in the pathogenesis of coronary artery disease (e.g. genetic factors, hyperlipidemia and others) or hypertensive vascular changes in the coronary circulation may not be as reversible as they are in the cerebral circulation. The well documented correlation between stroke, myocardial infarction and hypertension, as well as the proven efficacy of antihypertensive therapy in preventing cardiovascular events, underscores the importance of effective and sustained blood pressure control in these patients.

Adult↗
PubMed1996

Effect of age on kinetics of nitric oxide release in rat aorta and pulmonary artery.

Aging is an important determinant of vascular disease. Endothelium-derived nitric oxide (NO) is protective as a vasodilator and inhibitor of platelet function. This study was designed to directly measure effects of prolonged aging on endotheliai NO release in isolated blood vessels and to delineate differences between the systemic and pulmonary circulation. Aortas and pulmonary arteries from 5-6-mo-old (young), 18-19-mo-old (middle-aged), and 32-33-mo-old (old) normotensive female rats were used. Blood pressure and plasma estradiol-17beta (E2) remained unchanged. In isolated blood vessels, NO release was induced by the receptor-independent agonist calcium ionophore A23187 (10 micromol/liter) and measured in situ on the endothelial surface of vessels using a porphyrinic microsensor. In vessels suspended in organ chambers isometric tension was recorded. In the aorta, the initial rate of NO release and peak NO concentration were reduced in middle-aged and old rats (P < 0.0006 vs. young rats, n = 6). Furthermore, endothelium-dependent relaxations to calcium ionophore and acetylcholine (both 10(-10) - 10(-5) mol/liter) were also reduced in aortas from old as compared with young rats (n = 6, P < 0.05). The initial rate of NO release and peak NO concentration significantly correlated with maximal relaxation to calcium ionophore A23187 (correlation coefficients r - 0.916, P < 0.0018 and r = 0.961, P < 0.0001, respectively, n = 7). In pulmonary arteries, however, the initial rate of NO release as well as peak NO concentration did not decrease with age (n = 6 for each age group, NS). In both blood vessels, the NO release was unaffected by superoxide dismutase in all age groups (n = 6, NS). Thus, aging specifically reduces initial rate and peak concentrations of endothelial NO release from aorta but not pulmonary artery indicating reduced NO production. As arterial pressure did not change with aging, the chronic exposure of the aorta to higher pressure and/or pulsatility than in the pulmonary artery may be the cause. This appears important as NO plays a protective role by preventing vasoconstriction, thrombosis and atherosclerosis.

Aging↗
PubMed1996

Endothelin and calcium antagonists in the skin microcirculation of patients with coronary artery disease.

BACKGROUND: Endothelin, a potent endothelium-derived vasoconstrictor peptide, is elevated in coronary artery disease (CAD); however, its pathophysiological role is uncertain. Calcium antagonists are widely used in patients with CAD. Using laser Doppler flowmetry, we investigated the influence of two endothelin antagonists and the calcium antagonist diltiazem on endogenous and exogenous endothelin in the skin microcirculation of CAD patients and healthy control subjects. METHODS AND RESULTS: Both endothelin antagonists and diltiazem applied intradermally induced vasodilation in CAD patients, which was more pronounced with the ETA/ETB antagonist than with the ETA antagonist or diltiazem. Exogenous endothelin led to profound vasoconstriction in CAD patients and healthy volunteers. Both endothelin antagonists and diltiazem blunted the vasoconstriction to exogenous endothelin in CAD patients and young healthy volunteers and less so in old healthy volunteers. However, compared with both endothelin antagonists, a 10-times-higher dose of diltiazem was required. Systemic diltiazem (240 mg, slow release) attenuated endothelin-induced vasoconstriction in CAD patients. Neurogenic vasodilation to exogenous endothelin was inhibited by both endothelin antagonists. CONCLUSIONS: This study demonstrates that endogenous endothelin of CAD patients contributes to the regulation of vascular tone in the skin microcirculation not only through ETA receptors but also possibly through ETB receptors. Diltiazem inhibited endothelin-induced vasoconstriction, but endothelin antagonists were slightly more effective. Thus, endothelin antagonists represent potent new tools to interfere with the vascular effects of endothelin in CAD patients. Future studies must confirm these findings in other areas of the circulation.

Administration, Oral↗
PubMed1996

Increased activation of sympathetic nervous system and endothelin by mental stress in normotensive offspring of hypertensive parents.

BACKGROUND: The pathogenesis of essential hypertension is still uncertain, but genetic factors and the sympathetic nervous system are likely to be involved. Sympathetic nerve activity and hormonal circulatory control mechanisms, however, are affected by blood pressure itself. Hence, early functional changes are best investigated in normotensive subjects at risk to develop hypertension, such as normotensive offspring of hypertensive parents. METHODS AND RESULTS: Muscle sympathetic nerve activity (MSA) was measured in the peroneal nerve of 10 normotensive offspring of parents with essential hypertension and 8 offspring of normotensive parents. Measurements were performed under resting conditions, during a 10-minute period of hypoxia (12.5% O2/87.5% N2) and during a 3-minute mental stress test. The tests were separated by a 30-minute resting period. Plasma samples for determination of norepinephrine and endothelin were collected before and after the tests. Baseline values of MSA were comparable in offspring of hypertensive and normotensive parents. During hypoxia, MSA, heart rate, and norepinephrine and endothelin plasma levels increased in offspring of hypertensive and normotensive parents to a comparable degree, whereas no significant changes in blood pressure and plasma norepinephrine levels were observed in either group. During mental stress, MSA and plasma norepinephrine and endothelin increased only in offspring of hypertensive parents (P < .001 to .01). In parallel, blood pressure increased significantly only in offspring of hypertensive parents (P < .001 to .05) but heart rate increased in both groups (P < .001 to .05). CONCLUSIONS: The activity of the sympathetic nervous system and plasma norepinephrine and endothelin levels are increased during mental stress only in offspring of hypertensive parents, whereas the response to hypoxia was similar in offspring of hypertensive and normotensive parents, suggesting a genetically determined abnormal regulation of the sympathetic nervous system to certain stressful stimuli in offspring of hypertensive parents. This may play a role in the pathogenesis of essential hypertension.

Adult↗
PubMed1996

[Sympathetic nervous system and endothelial function in heart failure].

Congestive heart failure is a frequent cardiovascular disease with a poor prognosis in advanced stages. Activation of neurohumoral systems such as the renin-angiotensin system and the sympathetic nervous system as well as impairment of local regulatory mechanisms (i.e. adrenoceptors, endothelial factors) play an important role in the pathogenesis and prognosis of the disease. The increase in peripheral resistance is due to imbalance of vasoconstrictors and vasodilators in favour of the vasoconstrictors and to changes in endothelial function, i.e. impaired production of nitric oxide, increased production of endothelin. Sodium and volume retention as well as the activation of the renin-angiotensin system increase preload. The sympathetic nervous system, which is known to be an independent negative prognostic factor, is activated and interacts with the renin-angiotensin system; however, up to now it is uncertain, whether these pathophysiological findings contribute to the development of congestive heart failure or if they are only secondary phenomena.

Amino Acid Sequence↗
PubMed1996

[Therapeutic measures following acute myocardial infarct: differential use of PTCA, surgery and drugs].

Myocardial infarction represents a crossroads in the natural history of coronary artery disease. The prognosis is determined by the severity of coronary artery disease, infarct size (and hence ejection fraction), and age of the patient. After infarction, patients may remain symptomless, or suffer angina, silent ischemia, reinfarction, heart failure or sudden death. Hence patient management after infarction includes (1) estimation of risk, (2) the use of stress tests to detect ischemia and rhythm disorders, (3) PTCA or bypass if required and (4) medical therapy. Cardiac catheterization is indicated in patients with angina or silent ischemia, non-Q wave infarction or large infarctus; its use is less well established in patients without ischemia and left ventricular dysfunction, but this indication is nevertheless increasingly accepted. PTCA is primarily utilized in patients with single or two vessel disease, while coronary bypass surgery is indicated in patients with left main or three vessel disease. All these measures are designed to improve symptoms and prognosis. For secondary prevention medical therapy should be used to treat cardiovascular risk factors (antihypertensive drugs, lipid-lowering drugs etc.), to inhibit platelets (aspirin, ticlopidine) or coagulation (coumarins), to block neurohumoral activation (betablocker, ACE-inhibitors), for vasoconstriction (calcium channel blockers, nitrates) and to suppress arrhythmias. The large number of drugs requires reasoned use depending on the risk profile of the individual patient. Cardiovascular risk factors should be treated appropriately. Platelet inhibitors should be given to all patients except those with atrial fibrillation or large ventricles (coumarins). Betablockers reduce mortality, reinfarction and sudden death after infarction and hence should be used if no contraindications exist. ACE-inhibitors are particularly effective in improving symptoms and prognosis in patients with impaired left ventricular function. Calcium antagonists should be used with caution and only in patients with normal left ventricular function. Nitrates are primarily effective in improving symptoms in patients with angina or heart failure. Antiarrhythmic drugs (amiodarone) are only useful in patients with complex arrhythmias. Digitalis has been shown to improve symptoms in patients with heart failure, while other inotropic drugs are virtually no longer used. These guidelines allow reasoned differential therapy after myocardial infarction to the maximum benefit of the patient and at minimum cost.

Adrenergic beta-Antagonists↗
PubMed1996

Progressive withdrawal of muscle nerve sympathetic activity preceding vaso-vagal syncope during lower-body negative pressure.

We report the observation of a vaso-vagal syncope (VVS) occurring during lower body negative pressure in a young male volunteer. Recording of the peripheral blood flow, blood pressure and muscular sympathetic nerve activity revealed first a progressive withdrawal of muscle nerve sympathetic activity with redistribution of blood flow before the onset of the VVS.

Adult↗
PubMed1996

Endothelial function as an end-point in interventional trials: concepts, methods and current data.

SURROGATE END-POINTS: Pharmacotherapy of cardiovascular disease has been increasingly validated in large interventional trials to assess its efficacy, safety and costs. As endpoints, morbidity and mortality are evaluated. More recently, surrogate end-points have been included in interventional trials, both to increase our understanding of pathogenic mechanisms and for their potential use as markers of risk in patients. ENDOTHELIAL FUNCTION: The endothelium lies in a strategic anatomical position between the circulating blood and vascular smooth muscle and hence is a major local mediator of cardiovascular function. Also, endothelial cells are a target for mechanical forces and cardiovascular risk factors in the circulation. Thus, it is not surprising that their function becomes impaired at an early stage in the disease process. The cells are able to produce numerous proteins and mediators. This review focuses on nitric oxide and endothelin-1, which are endothelium-derived relaxing and constrictor factors, respectively. Nitric oxide also prevents platelet adhesion and aggregation and the adhesion of monocytes. Both substances also affect vascular structure in that nitric oxide inhibits while endothelin stimulates vascular smooth muscle proliferation and migration. MEASUREMENTS OF ENDOTHELIAL FUNCTION: Endothelial function and the effects of nitric oxide and endothelin in particular can be evaluated in the coronary circulation by quantitative coronary angiography and Doppler flow wire, and in the peripheral circulation with plethysmography and new ultrasound/Doppler devices. In these experimental set-ups, lipid-lowering drugs and angiotensin converting enzyme (ACE) inhibitors have been evaluated. Lipid-lowering drugs improve endothelium-dependent vasodilation in the coronary and forearm circulation of patients with hyperlipidemia and atherosclerosis. Similarly, ACE inhibitors improve coronary vasomotion in patients with coronary artery disease and normal lipid levels. In hypertension, ACE inhibitors have failed to improve endothelium-dependent vasodilation, while studies with other drugs are planned. CONCLUSIONS: Endothelial function can now be assessed precisely in patients in vivo, in both the coronary and the peripheral circulation. Tests can detect early dysfunction in patients with a risk of cardiovascular disease and the possible effects of drugs on endothelial function. Large interventional trials are needed to establish how far endothelial dysfunction can or cannot predict clinical outcome.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Lipids and endothelial function: effects of lipid-lowering and other therapeutic interventions.

Coronary arteries are regulated by neuronal mechanisms, hormones and paracrine mediators. The importance of endothelium-dependent mechanisms has recently been recognized. The endothelium responds to mechanical and chemical signals from the blood by releasing mediators that modulate vascular tone and structure, platelet function, coagulation and monocyte adhesion. Important relaxing factors are nitric oxide, prostacyclin and a putative hyperpolarizing factor. Nitric oxide also inhibits smooth muscle proliferation and, together with prostacyclin, platelet function. Bradykinin-induced nitric oxide production is reduced by angiotensin-converting enzyme. Endothelin-1, thromboxane A2 and prostaglandin H2 are contracting factors. Thromboxane A2 and prostaglandin H2 activate platelets, while endothelin has no direct platelet effects, but causes smooth muscle proliferation. In hypercholestermia, endothelium-dependent relaxation is impaired and contraction as well as adhesion of monocytes and platelets enhanced. Pharmacological correction of hyperlipidemia by statins also improves or normalizes endothelial dysfunction in patients. Angiotensin-converting enzyme inhibitors have similar effects.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

[Molecular and cellular mechanisms of arteriosclerosis and restenosis: possibilities of gene therapy].

Atherosclerosis and its consequences account for most of morbidity and mortality in Western countries. Atherosclerosis develops over a period of decades and has a complex pathogenesis. It is a disease of the intima and primarily involves four cell types, i.e., endothelial and vascular smooth muscle cells, monocytes and platelets. In recent years, knowledge on the cellular and molecular mechanisms of these cells and their alterations by cardiovascular risk factors and in atherosclerosis has greatly expanded. In particular, it became clear that endothelial cells play a crucial role in the regulation of platelet function, coagulation as well as vascular tone and structure. Interestingly, endothelial dysfunction occurs early, particularly if cardiovascular risk factors such as hyperlipidemia, hypertension and diabetes are present. This could lead to adhesion of circulating platelets and monocytes and increased accumulation of lipids in the subintima as well as increased contraction, migration and proliferation of vascular smooth muscle cells. The fact that atherosclerosis develops only in certain, but not in other parts of the circulation, however, has rarely been considered. With the development of molecular biology techniques it became possible to clone differentially expressed genes in vessels with or without atherosclerosis; this in turn allows to better characterize the molecular and cellular mechanisms of the disease. The search for such candidate genes could set the basis for future genetic interventions. This therapeutic approach is likely to reach clinical importance particularly in monogenetic diseases (i.e., familial hypercholesterinemia), while its use in complex polygenetic diseases such as atherosclerosis is more difficult. Restenosis, however, may be accessible to gene therapy earlier on as it is amenable to local gene transfection.

Arteriosclerosis↗
PubMed1995

[Molecular medicine and gene therapy as exemplified with arteriosclerosis and restenosis].

Atherosclerosis and its consequences account for most morbidity and mortality in Western countries. Atherosclerosis develops over a period of decades and has a complex pathogenesis. It is a disease of the intima and primarily involves four cell types, i.e. endothelial and vascular smooth muscle cells, monocytes and platelets. In recent years, elucidation of the cellular and molecular mechanisms of these cells, and their alterations by cardiovascular risk factors and in atherosclerosis, has markedly expanded knowledge of this disease. In particular, it became clear that endothelial cells play a crucial role in the regulation of platelet function and coagulation, as well as vascular tone and structure. Interestingly, endothelial dysfunction occurs early on in the presence of cardiovascular risk factors such as hyperlipidemia, hypertension and diabetes. This could lead to adhesion of circulating platelets and monocytes, increased accumulation of lipids in the subintima, increased contraction, migration and proliferation of vascular smooth muscle cells. The fact that atherosclerosis develops only in some but not in other parts of the circulation, however, has rarely been considered. With the development of molecular biology it has now become possible to clone differentially expressed genes in vessels with or without atherosclerosis; this in turn makes it possible to characterize better the molecular and cellular mechanisms of the disease. The search for such candidate genes could form the basis for future genetic interventions. This therapeutic approach is likely to assume clinical importance, particularly in monogenetic diseases (i.e. familial hypercholesteremia), while its use in complex polygenetic diseases such as atherosclerosis is more difficult. Restenosis, however, may be accessible to gene therapy earlier on as it is accessible to local gene transfection.

Arteriosclerosis↗
PubMed1995

Increased activity of constitutive nitric oxide synthase in cardiac endothelium in spontaneous hypertension.

BACKGROUND: We analyzed the activity of nitric oxide synthase in the rat heart to study whether this activity is affected by high blood pressure. Hearts from young (3 to 4 weeks old) and adult (15 to 25 weeks old) Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were excised and frozen in liquid nitrogen. The activities of Ca(2+)-dependent (cNOS) and Ca(2+)-independent (iNOS) were determined in homogenized tissues by measuring the conversion of [14C]-L-arginine to [14C]-L-citrulline in the presence or absence of either EGTA (1 mmol/L) or EGTA plus NG-nitro-L-arginine methyl ester (L-NAME, 1 mmol/L each). METHODS AND RESULTS: Arterial pressure was higher in adult SHR than in young SHR and WKY rats of both ages (P < .01). The cNOS activity was two to three times higher in hypertensive than in normotensive hearts (P = .01 to P = .04). No significant activity of iNOS was detected in any tissue. Studies of the right and left ventricles demonstrated a higher cNOS activity in the left sides of the hearts of adult SHR (P < .05). No differences were found in hearts from WKY rats. Selective removal of endocardial or coronary endothelial cells in hearts of SHR and WKY rats substantially reduced cNOS activity (P < .01). CONCLUSIONS: The cNOS activity is upregulated in cardiac endothelial cells of genetically hypertensive rats. The high activity of cardiac cNOS is related to increased arterial pressure of these animals. We propose that in the heart, endothelial cells respond with a higher production of nitric oxide as a compensatory mechanism against high blood pressure and its damaging effects in this organ.

Amino Acid Oxidoreductases↗
PubMed1995

[Beta blockers in heart insufficiency].

Congestive heart failure is common. Since prognosis depends on activation of neurohumoral systems, treatment with beta-blocking agents seems to be appropriate in spite of their negative inotropic effects. According to the results of the studies published hitherto, mortality was not reduced by beta blockers, but the clinical course, symptoms and hemodynamic parameters were influenced positively, particularly in patients with congestive cardiomyopathy. Further studies are necessary in order to establish specific advantages of beta-blocking agents in patients with heart failure, before they are recommended for routine therapy in medical practice.

Adrenergic beta-Antagonists↗
PubMed1995

Local regulation of the coronary circulation in health and disease: role of nitric oxide and endothelin.

Coronary artery disease is the leading cause of morbidity and mortality in western countries. Its pathogenesis is unknown, but involves enhanced vasoconstriction, increased interaction of platelets and monocytes with the vessel wall, as well as proliferation, migration and extracellular matrix formation of vascular smooth muscle. The endothelium lies in a strategic anatomical position between circulating blood and vascular smooth muscle cells. This supports the concept that dysfunction of these cells significantly contributes to coronary artery disease. Besides other mediators, endothelial cells are a source of nitric oxide and endothelin. Nitric oxide is a vasodilator, an inhibitor of both platelet function and proliferation and migration of vascular smooth muscle. Endothelin is a potent vasoconstrictor that facilitates proliferation. Under pathological conditions, in particular the presence of cardiovascular risk factors, endothelial dysfunction occurs and is a major contributor to the increase in platelet vessel wall interaction, vasoconstriction and proliferation in the coronary system. Endothelium-dependent vasodilation is usually reduced and endothelium-dependent constrictor responses, as well as endothelin production, are augmented. Hence, endothelial cells are important targets and mediators of coronary artery disease.

Animals↗