We recently showed that cytochrome P450 (P450) contributes importantly to canine coronary microvascular dilatation in vivo. P450 metabolizes arachidonic acid (AA) to epoxyeicosatrienoic acids (EETs), which our laboratory has shown are potent dilators of coronary microvessels. We, therefore, tested the hypothesis that AA-induced coronary microvascular dilation is mediated in part through a P450 pathway. Adult mongrel dogs (n=22) of either sex were anesthetized. A thoracotomy was performed and coronary arterioles (<100 μm) were observed using stroboscopic epi-illumination during the topical application of AA (1, 5, 10 μM) Coronary microvascular responses were examined in the presence of indomethacin (Indo, 5 mg/kg iv) and Indo plus clotrimazole (CLO, 1.8 μM topically, a cytochrome P450 monooxygenase inhibitor). Results (mean ± SEM, *p<0.05 vs baseline). AA (μM. topically) 1 5 10 Baseline 14 ± 4 35 ± 3 61 ± 5 Indo + CLO 9 ± 3 29 ± 3 48 ± 2* Indo alone did not alter AA-induced dilatation. However, Indo+CLO attenuated AA-induced dilatation, whereas responses to nitroprusside were unaffected. These results suggest that AA induced coronary microvascular dilation is mediated in part by a cytochrome P450 pathway.
|Original language||English (US)|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology