Superoxide and coronary vasodilation to bradykinin (BK) in the rat

D. Fulton, J. C. McGiff, J. Quilley

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The coronary vasodilator effect of BK in the rat is dependent on sequential activation of phospholipase C and A2, with involvement of cytochrome P450 monooxygenase (P450) and activation of Ca -activated K channels, implicating an unidentified hyperpolarizing factor that is generated via P450 metabolism of arachidonic acid (AA). As P450 activity generates free radicals such as Superoxide (Oj), we addressed the contribution of OJ to the coronary vasodilator action of BK in the rat. Using rat renal cortical microsomes as a source of P450 we first verified that P450-dependent metabolism of AA generated O2- which was detected by chemiluminescence with lucigenin. The signal was almost abolished by inhibition of P450 with clotrimazole and the oj scavenger, 4,5-dihydroxy1,3-benzene-disulfonic acid (Tiron). The rat heart was perfused with buffer containing nitroarginine (50uM) and indomethacin (2.8 uM) to eliminate NO and prostaglandins and elevate perfusion pressure (PP) from ca 40mmHg to 140 mmHg. Dose-dependent vasodilator responses to BK (10-1000ng), which reduced PP between 22+4 and 82±4 mmHg, were unaffected by SOD (100U/ml) plus catalase (400U/ml), a combination that abolished dilator responses to H2O2. Similarly the Of scavengers, Tiron and 4-hydroxy-tempo, were without effect on vasodilator responses to BK. Finally, baseline Oj generation, detected by chemiluminescence, in cardiac slices and perfused hearts was unchanged in response to BK or AA. In contrast to cerebral vessels, the coronary vasodilator effect of BK is independent of C% which can be excluded as a hyperpolarizing factor mediating BK-induced vasodilation in the rat heart.

Original languageEnglish (US)
JournalFASEB Journal
Issue number3
StatePublished - Dec 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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