Prostaglandin I2 does not contribute to the hypotensive effect of the superoxide dismutase mimetic Tempo in rats with aortic coarctation-induced hypertension.
This study was designed to investigate the contribution of prostaglandins to the vasodepressor effect of the superoxide dismutase mimetic Tempo in rats made hypertensive by ligation of the abdominal aorta at a point between the left and right renal arteries. Rings of thoracic aorta taken from rats with aortic coarctation released more 6-keto-PGF1alpha (a non-enzymatic product of PGI2 degradation) in the presence than in the absence of Tempo (1 mmol/L; 35.3 +/- 10.1 versus 13.6 +/- 2.6 pg/mg tissue). However, Tempo administered intravenously (2 mg/kg bolus injection plus infusion at 3 mg/kg/h) to rats with aortic coarctation did not increase significantly the concentration of 6-keto-PGF1alpha in vena cava blood. Treatment with Tempo did not affect the arterial pressure of un-operated normotensive rats but promptly decreased the arterial pressure of rats with aortic coarctation-induced hypertension (from 178 +/- 2 to 125 +/- 6 mmHg). The vasodepressor effect of Tempo in hypertensive animals was not affected by pretreatment with indomethacin to inhibit prostaglandin synthesis. These data argue against the hypothesis that PGI2 contributes to the acute hypotensive effect of Tempo in rats with aortic coarctation.
DelliPizzi
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Department of Biology, Manhattan College, Riverdale, New York 10471, USA. annmarie.dellipizzi@manhattan.edu
Guan
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Dinocca
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Nasjletti
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D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D001017:Aortic Coarctation / Q000150:complications* / Q000503:physiopathology; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000097:blood*; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology
D000959:Antihypertensive Agents; D003497:Cyclic N-Oxides; D016861:Cyclooxygenase Inhibitors; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D013482:Superoxide Dismutase; C003959:TEMPO; D007213:Indomethacin