Prostaglandin endoperoxide‐dependent vasospasm in bovine coronary arteries after nitration of prostacyclin synthase
M Zou, M Jendral, V Ullrich - British journal of pharmacology, 1999 - Wiley Online Library
M Zou, M Jendral, V Ullrich
British journal of pharmacology, 1999•Wiley Online LibraryIn 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 μmol L− 1 ONOO− impaired A‐II‐induced
vasorelaxation and caused a second long lasting constriction phase. Indomethacin (10− 5m)
prevented both effects. U51605, a dual blocker of PGI2‐synthase and thromboxane (TX) A2 …
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 μmol L− 1 ONOO− impaired A‐II‐induced
vasorelaxation and caused a second long lasting constriction phase. Indomethacin (10− 5m)
prevented both effects. U51605, a dual blocker of PGI2‐synthase and thromboxane (TX) A2 …
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 μmol L−1 ONOO− impaired A‐II‐induced vasorelaxation and caused a second long lasting constriction phase. Indomethacin (10−5M) prevented both effects. U51605, a dual blocker of PGI2‐synthase and thromboxane (TX)A2‐synthase mimicked the effects of ONOO−.
- 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 F2α could be excluded a direct action of unmetabolized PGH2 on the TXA2/PGH2 receptor was postulated.
- ONOO− dose‐dependently inhibited the conversion of 14C‐PGH2 into 6‐keto‐PGF1α in isolated bovine coronary arteries with an IC50‐value of 100 nM.
- 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 μmol l−1 ONOO−.
- 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.
British Journal of Pharmacology (1999) 126, 1283–1292; doi:10.1038/sj.bjp.0702434
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