endothelin-1 and Angina-Pectoris--Variant

Recent studies showed that coronary artery spasm may be due to disturbances of secretory and excretory endothelial activity in atherosclerotic coronary artery. However, this theory does not explain the reasons of coronary artery spasm when endothelium is not damaged. There must be other patomechanisms of coronary artery spasm. The aim of our study was examination of calcium efflux through the lymphocytic cell membrane and determination of endothelin-1 plasma levels in patients with variant angina in order to define the participation of these factors in pathogenesis of coronary artery spasm. The survey was made in 76 patients with ischaemic heart disease. All patients were divided into 2 groups. The first group consisted of 48 patients with variant angina (d.b.s.), the other consisted of 28 patients with stable angina (d.b.w.). The control group (g.k.) was composed of 25 healthy people. Patients were administered 100 ml of trometamol (TRIS, pH = 10.5) intravenously for 5 minutes. After stopping the infusion the examined patient was breathing deeply for 5 minutes at a rate of 40/min. The endothelin-1 (ET-1) plasma levels and transmembrane calcium transport in lymphocytes were determined before and just after the hyperventilation test, as well as 10 minutes after the test. ET-1 plasma concentrations were estimated with a radioimmunologic assay. The method of estimation of transmembrane calcium transport was elaborated in Laboratory of Department of Cardiology of Medical University of Wrocław. We showed that ET-1 plasma levels and transmembrane calcium transport in patients with d.b.s. before the test were normal. There was an increase in transmembrane calcium efflux in patients with d.b.s. during coronary artery spasm that had been caused by ET-1. ET-1 plasma levels were still high 10 min. after the coronary artery spasm. Disturbances of transmembrane calcium transport and increased endothelin-1 plasma level may be the primary factors responsible for coronary artery spasm.

Topics: Adult; Aged; Angina Pectoris; Angina Pectoris, Variant; Calcium; Endothelin-1; Female; Humans; Ion Transport; Lymphocytes; Male; Middle Aged; Tromethamine

The role of endothelial dysfunction in coronary vasospasm is controversial. We hypothesized that reactive oxygen species (ROS) and endothelin-1 (ET-1) are plausible candidates as the mediator of vasospasm is linked to endothelial dysfunction. In a pig model with repetitive endothelial injury in coronary arteries, intracoronary administration of serotonin induced a vasospasm at the endothelial injury site. The level of endothelin-converting enzyme was upregulated at that site where, upon exposure to serotonin, there were also increases in p47(phox), ROS, and ET-1 fluorescence intensities, and myosin light chain phosphorylation and RhoA activation were detected. The nicotinamide adenine dinucleotide phosphate oxidase inhibitor, apocynin, had the effect of extinguishing not only ROS but also the appearance of ET-1. The chronic blockade of endothelin type-A receptor prevented a serotonin-triggered vasospasm along with the inhibition of ROS generation and myosin light chain phosphorylation. Under the coronary artery endothelial dysfunction, ET-1 is essential for an ROS-dependent coronary vasospasm. Our findings suggest that endothelial dysfunction plays a critical role in clinically defined human Prinzmetal angina.

Topics: Acetophenones; Angina Pectoris, Variant; Animals; Aspartic Acid Endopeptidases; Coronary Angiography; Coronary Vasospasm; Disease Models, Animal; Endothelin A Receptor Antagonists; Endothelin-1; Endothelin-Converting Enzymes; Endothelium, Vascular; Enzyme Inhibitors; Metalloendopeptidases; Myosin Light Chains; NADPH Oxidases; Phosphorylation; Pyrimidines; Reactive Oxygen Species; Receptor, Endothelin A; rhoA GTP-Binding Protein; Serotonin; Signal Transduction; Sulfonamides; Swine; Time Factors; Vasoconstriction

The incidence of variant angina in oriental patients is higher than in patients from the Western world. Endothelin-1 (ET-1) seems to be associated with coronary vasospasm in variant angina, suggesting that ET-1 gene variants may be important in coronary vasospasm in variant angina. We wanted to assess potential association between Korean variant angina and three polymorphisms of the ET-1 gene, which include the +138delA polymorphism in exon 1, G8002A polymorphism in intron 4 and Lys198Asn polymorphism in exon 5.. A total of 97 patients with variant angina and 111 healthy controls were studied. Analyses of the +138delA, G8002A and Lys198Asn polymorphisms were carried out by polymerase chain reaction-restriction fragment length polymorphism and haplotype techniques.. The frequency of mutant 138delA allele was lower in the angina group than in controls [p=0.003, odds ratio (OR)=0.42] and the frequencies of A8002 or Asn198 were significantly higher in the variant angina group than in controls (p=0.005, OR=2.17 or p=0.009, OR=1.75, respectively). According to haplotype analysis, 4A/A8002/Asn198 haplotype was significantly associated with the disease (p=0.0162, OR=2.33) and 3A/G8002/Lys198 haplotype was protective against the disease (p=0.0043, OR=0.54).. The ET-1 gene polymorphisms, such as +138delA, G8002A and Lys198Asn polymorphisms, seem to be associated with variant angina in Korean patients.

Topics: Adult; Aged; Angina Pectoris, Variant; Asian People; Endothelin-1; Female; Gene Deletion; Gene Frequency; Genotype; Haplotypes; Humans; Korea; Logistic Models; Male; Middle Aged; Odds Ratio; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Risk Factors

Vasospastic angina as a result of alcohol ingestion has been reported, but the mechanism of alcohol-induced coronary artery spasm is presently unknown. This report presents 2 cases of alcohol-induced variant angina (VA) with elevated levels of plasma endothelin-1 after alcohol ingestion. In case 1, the plasma endothelin-1 concentration was 3.15 pg/ml before drinking (normal <2.30 pg/ml) and increased to 4.09 pg/ml when measured 5 h after alcohol ingestion. After 2 months of abstinence, the plasma endothelin-1 concentration was 2.88 pg/ml and 6 months after abstinence, it decreased to 2.03 pg/ml (normal range). In case 2, the plasma endothelin-1 concentration was 2.44 pg/ml before drinking and increased to 4.36 pg/ml when measured 5 h after alcohol ingestion. After 2 months of abstinence, the plasma endothelin-1 concentration was 3.04 pg/ml and 6 months after abstinence, it decreased to 2.09 pg/ml (normal range). These 2 cases suggest that a relationship may exist between alcohol-induced VA and elevation in the plasma endothelin-1 concentration after alcohol ingestion.

Topics: Aged; Alcoholic Beverages; Angina Pectoris, Variant; Chest Pain; Coronary Angiography; Coronary Vasospasm; Electrocardiography; Endothelin-1; Ethanol; Humans; Male; Temperance; Time Factors