3-nitrotyrosine and Coronary-Vasospasm

Endothelial dysfunction of the coronary arteries caused by oxidative stress plays an important role in the pathogenesis of coronary vasospasm. However, it is not clear whether circulating biomarkers for oxidative stress are altered after coronary vasospasm. We investigated temporal changes in the levels of oxidative stress biomarkers after coronary vasospasm induced by intracoronary acetylcholine provocation testing, resulting in transient myocardial ischemia.. Thirty consecutive patients with suspected vasospastic angina pectoris (VSAP) were enrolled in the study. Patients were categorized into the VSAP-positive group (n=14) and the VSAP-negative group (n=16) on the basis of test results. Serum samples were examined for the levels of the oxidative stress markers 4-hydroxynonenal (HNE) and nitrotyrosine (NT) before, and 15min, 3h, and 12h after the provocation test. The serum HNE levels did not change in either group after the test. The serum NT levels in the VSAP-positive group significantly increased at 3h and 12h after the test (11.3±3.3μg/ml at 3h, p=0.015, and 12.1±5.7μg/ml at 12h, p=0.03), as compared with baseline (8.1±3.2μg/ml). In the VSAP-negative group, the serum NT levels significantly decreased from baseline at each of the 3 time points.. Serum NT significantly increased after coronary vasospasm induced by acetylcholine provocation, suggesting that serum NT could be a biomarker of transient myocardial ischemia and could contribute to the development of VSAP.

Topics: Acetylcholine; Aged; Aldehydes; Biomarkers; Coronary Vasospasm; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Oxidative Stress; Tyrosine

In the present study we used a bioassay to study the effects of peroxynitrite (ONOO-) on angiotensin II (A-II)-triggered tension in isolated bovine coronary arteries in order to show the consequences of the previously reported PGI2-synthase inhibition by ONOO- in this model. The following results were obtained: 1. 1 micromol L(-1) ONOO- impaired A-II-induced vasorelaxation and caused a second long lasting constriction phase. Indomethacin (10(-5)M) prevented both effects. U51605, a dual blocker of PGI2-synthase and thromboxane (TX)A2-synthase mimicked the effects of ONOO-. 2. The selective TXA2/prostaglandin endoperoxide (PGH2) receptor antagonist SQ29548 antagonized the second vasoconstriction phase after ONOO- -treatment. Since a generation of TXA2 and 8-iso-prostaglandin F2alpha could be excluded a direct action of unmetabolized PGH2 on the TXA2/PGH2 receptor was postulated. 3. ONOO- dose-dependently inhibited the conversion of 14C-PGH2 into 6-keto-PGF1alpha in isolated bovine coronary arteries with an IC50-value of 100 nM. 4. Immunoprecipitation of 3-nitrotyrosine-containing proteins with a monoclonal antibody revealed PGI2-synthase as the only nitrated protein in bovine coronary arteries treated with 1 micromol 1(-1) ONOO-. 5. Using immunohistochemistry a co-localization of PGI2-synthase and nitrotyrosine-containing proteins was clearly visible in both endothelial and vascular smooth muscle cells. We concluded that ONOO- not only eliminated the vasodilatory, growth-inhibiting, antithrombotic and antiadhesive effects of PGI2 but also allowed and promoted an action of the potent vasoconstrictor, prothrombotic agent, growth promoter, and leukocyte adherer, PGH2.

Topics: Angiotensin II; Animals; Carbon Radioisotopes; Cattle; Coronary Vasospasm; Coronary Vessels; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Dinoprostone; Epoprostenol; Immunohistochemistry; In Vitro Techniques; Intramolecular Oxidoreductases; Nitrates; Oxidants; Potassium Chloride; Prostaglandin Antagonists; Prostaglandin H2; Prostaglandins; Prostaglandins H; Proteins; Tyrosine; Vasoconstriction; Vasodilation