neuropeptide-y and Angina-Pectoris

One of the causes of coronary artery spasm in patients with variant angina could be a disturbed interaction between the vasodilating action of endothelial derived relaxing factor and the vasospastic action of neuropeptide Y and thromboxane B2. The aim of this study was a verification of the participation of neuropeptide Y and thromboxane B2 in etiopathogenesis of the coronary artery spasm in patients with variant angina. The survey was made in 38 patients with variant angina and in 18 patients with chronic stable angina pectoris. The control group consisted of 20 healthy persons. Before the hyperventilation test, during which the person under test has been breathing with a frequency of 40/minute through 5 minutes, the Tris (tromethamol) of pH = 10.5 has been given in intravenous infusion lasting for 5 minutes. The neuropeptide Y and thromboxane B2 plasma levels have been determined just before the hyperventilation test, just after the termination of the test and 10 minutes after the termination of the test. Neuropeptide Y and thromboxane B2 plasma levels have been determined with a radioimmunologic method. It has been recorded that during the hyperventilation test in all of the 38 patients with variant angina the clinical and the electrocardiographic symptoms of the coronary artery spasm have appeared--but these have not appeared in patients with chronic stable angina pectoris and in healthy persons. The level of neuropeptide Y in patients with variant angina before the test, just at its end and as well as 10 min. after completing of the hyperventilation test, was significantly higher compared with the level in patients with chronic stable angina pectoris and controls. Contrary to chronic stable angina pectoris patients and controls, in variant angina group the level of neuropeptide Y increased rapidly at the end of the test and further elevation in neuropeptide Y level was observed 10 min. after the test. There was no difference in basal thromboxane B2 levels between angina patients and controls. At the end of hyperventilation test in variant angina group thromboxane B2 level significantly increased and remained on this level until 10 min. after the test. Significant increase of neuropeptide Y and thromboxane B2 plasma levels in variant angina patients during artery coronary spasm induced by hyperventilation test suggests the contribution of these humoral factors to the pathogenesis of vasospastic episodes in angina patients.

Topics: Adult; Angina Pectoris; Angina Pectoris, Variant; Chronic Disease; Female; Humans; Male; Middle Aged; Neuropeptide Y; Thromboxane B2

Neurohormones may influence vascular tone both during and after exercise. Neuropeptide Y (NPY), which is costored and released with norepinephrine (NE) during sympathetic activity, is a potent vasoconstrictor with a relatively long half-life. We therefore examined its possible association with the ischemic response to exercise in patients with coronary artery disease.. Twenty-nine male patients with effort-induced angina pectoris underwent a symptom-limited exercise test. In addition to conventional ST-segment analysis, we examined ischemia on the basis of heart rate (HR)-adjusted ST-segment changes through calculation of the ST/HR slope during the final 4 minutes of exercise and of the ST/HR recovery loop after exercise. Blood samples were taken before, during, and after exercise for an analysis of several neurohormones. Mean ST-segment depression was -223+/-20.2 microV (P:<0.0001) just before the termination of exercise, followed by a gradual normalization, but it remained significant after 10 minutes (-49+/-8.9 microV, P:<0.0001). At the end of exercise, the ST/HR slope, which reflects myocardial ischemia, was -6.0+/-0.77 microV/HR. In most patients, ST-segment levels at a given HR were lower during recovery than during exercise, here referred to as ST "deficit." Exercise increased the plasma levels of NPY, NE, epinephrine, and N-terminal proatrial natriuretic peptide, but big endothelin remained unchanged. Although NE and epinephrine peaked at maximal exercise, the highest levels of NPY and N-terminal proatrial natriuretic peptide were observed 4 minutes after exercise. The maximal increase in the NPY correlated significantly with ST-segment depression at 3 minutes after exercise (r=-0.61, P:= 0.0005), the ST deficit at the corresponding time point (r=-0.66, P:= 0.0001), and the duration of ST-segment depression after exercise (r= 0.42, P:=0.02). In contrast, no such correlations were found for NE.. The present study has for the first time demonstrated a correlation between plasma NPY levels and the degree and duration of ST-segment depression after exercise in patients with coronary artery disease, which suggests that NPY may contribute to myocardial ischemia in these patients.

Topics: Analysis of Variance; Angina Pectoris; Atrial Natriuretic Factor; Coronary Disease; Electrocardiography; Endothelin-1; Endothelins; Epinephrine; Exercise Test; Heart Rate; Humans; Male; Middle Aged; Neuropeptide Y; Norepinephrine; Protein Precursors; Time Factors

To investigate the change characteristics of neuropeptide Y (NPY) release during acute myocardial ischemia period.. The animal test was carried out in in situ perfused guinea pig hearts with intact sympathetic innervation. Electrical stimulation-evoked exocytotic release of NPY during ischemia and reperfusion was tested by radioimmunoassay (RIA). The plasma NPY concentrations were measured in patients with acute myocardial infarction (AMI) and angina pectoris (AP) in different times.. Electric stimulation of the left ganglion in guinea pig heart evoked an exocytic release of neuropeptide Y. Stimulation after 20 minutes of global ischemia (S2), compared with control period stimulation (S1) produced the inhibition of NPY to a certain extent (S2/S1: 0.72, P < 0.05), whereas the inhibition of NPY release disappeared after 5 minutes reperfusion (with S2/S1 of 1.01, P > 0.05). Ischemia alone, without the electric stimulation, did not apparently induce NPY release. The clinical test found that the plasma NPY level was increased significantly during the acute ischemia attack period of coronary heart disease (CHD). The plasma NPY level reached peak (136.3 +/- 66.5 pg/ml) in patients during the first day after AMI. It began to decrease from the third day and came to normal level in the end of the first week. The plasma NPY level was 159.3 +/- 98.5 pg/ml in AP patients during angina attack. After two weeks treatment, the plasma NPY level was decreased to 118.9 +/- 54.3 pg/ml (P < 0.05).. The NPY release of global ischemia have some relation with sympathetic nerve activity. At the early stage of ischemia, NPY release is inhibited to some degree and the inhibition factors will fade away on reperfusion. NPY interferes with the pathogenesis and the pathophysiolgy.

Topics: Aged; Angina Pectoris; Animals; Electric Stimulation; Guinea Pigs; Humans; In Vitro Techniques; Middle Aged; Myocardial Infarction; Neuropeptide Y; Sympathetic Nervous System

Plasma levels of neuropeptide Y-like immunoreactivity (NPY-LI) and noradrenaline were studied for 25 h in 22 patients with acute ischaemic heart disease. On admission, NPY-LI levels were above normal in 16 patients, and 20 patients had increased noradrenaline levels. The initial plasma NPY-LI did not differ between patients with acute myocardial infarction (AMI) and angina pectoris. Initial plasma noradrenaline levels were higher in patients with AMI than in those with angina pectoris. Plasma levels of noradrenaline remained elevated in AMI patients, but decreased towards normal values in patients with angina pectoris. Levels of NPY-LI returned to normal within 25 h in all patients. Tachycardia and left ventricular failure were related to high NPY-LI and noradrenaline levels. A positive correlation was found between noradrenaline and NPY-LI in plasma. It is suggested that neuropeptide Y (NPY), an endogenous vasoconstrictor peptide, should be considered as one of the mediators involved in the cardiovascular response to sympathetic activation induced by myocardial ischaemia.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Blood Pressure; Female; Heart Rate; Humans; Male; Middle Aged; Myocardial Infarction; Neuropeptide Y; Norepinephrine; Pain Measurement; Sampling Studies; Time Factors

STUDY OBJECTIVE - The aim of the study was to measure plasma neuropeptide Y, which is related to sympathetic nerve stimulation, in patients admitted to a coronary care unit and to relate the findings to clinical information. DESIGN - Plasma neuropeptide Y was measured on admission and the results were related to the cause of admission and to clinical information collected prospectively and retrospectively. SUBJECTS - Plasma subjects were obtained from 377 consecutive daytime admissions to the coronary care unit at Södersjukhuset. Results of only the first sample in each patient are included in this study, so 45 cases observed more than once (readmitted patients) were omitted. Six samples were abandoned because of technical failures. The study therefore comprises 326 patients. Clinical diagnoses were defined as acute myocardial infarction, arrhythmia, angina pectoris, and miscellaneous (all other diagnoses). Heart failure was defined according to a modified Killip scheme. MEASUREMENTS and RESULTS - Neuropeptide Y like immunoreactivity was measured by radio-immunoassay. Plasma concentrations above normal (greater than 30 pmol.litre-1) were found in association with: increased age, female sex, diuretic treatment, tachycardia, arterial hypotension, increased respiratory rate, and mortality in the unit. There was a strong relationship between high neuropeptide Y concentrations and: moderate left heart failure (63%), pulmonary oedema (90%), and cardiogenic shock (100%). Of patients without heart failure only 25% had raised neuropeptide Y. In multivariate analysis, the severity of heart failure (Killip class), heart rate and respiratory rate were the only variables that were significantly and independently related to plasma neuropeptide Y. CONCLUSIONS - The presence and degree of circulatory disturbance, in particular tachycardia and left heart failure, were strongly related to increased plasma concentrations of neuropeptide Y in coronary care patients.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Arrhythmias, Cardiac; Coronary Care Units; Diuretics; Epinephrine; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Neuropeptide Y; Norepinephrine; Pilot Projects; Pulmonary Edema; Risk Factors; Shock, Cardiogenic

Neuropeptide Y was infused into a coronary artery of 6 patients with typical angina but no significant coronary stenosis. 3 patients had transient myocardial ischaemia, shown by typical pain and electrocardiographic change, at doses of 0.2 pmol/kg per min in 2 patients and 1.0 pmol/kg per min in 1 patient. The arteriographic appearances suggested constriction of small vessels rather than constriction of epicardial coronary arteries. The ischaemia was completely reversed by intracoronary administration of isosorbide dinitrate with no adverse sequelae. This is the first demonstration of myocardial ischaemia in man induced by a peptide neurotransmitter.

Topics: Adult; Aged; Angina Pectoris; Angiography; Coronary Angiography; Female; Humans; Infusions, Intra-Arterial; Isosorbide Dinitrate; Middle Aged; Myocardial Infarction; Neuropeptide Y