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Cytochrome P450‐dependent effects of bradykinin in the rat heart
Author(s) -
Fulton D.,
Mahboubi K.,
McGiff J.C.,
Quilley J.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb14911.x
Subject(s) - bradykinin , nitroarginine , vasodilation , pharmacology , arachidonic acid , chemistry , medicine , endocrinology , nitric oxide , nitric oxide synthase , biochemistry , enzyme , receptor
1 Vasodilator responses to bradykinin (BK) in the rat heart are reported to be independent of NO and cyclo‐oxygenase/lipoxygenase products of arachidonic acid (AA). 2 We verified that inhibition of NO synthase with l ‐nitroarginine (50 μ m ) and cyclo‐oxygenase with indomethacin (2.8 μ m ) were without effect on vasodilator responses to BK (10–1000 ng) in the Langendorff rat heart preparation. 3 l ‐Nitroarginine elevated perfusion pressure, signifying a crucial role of NO in the maintenance of basal vasculature tone. 4 In hearts treated with l ‐nitroarginine to eliminate NO and elevate perfusion pressure, vasodilator responses were reduced by inhibitors of cytochrome P450 (P450), clotrimazole (1 μ m ) and 7‐ethoxyresorufin (1 μ m ). 17‐Octadecynoic acid (17‐ODYA 2 μ m ), a mechanism based inhibitor of P450‐dependent metabolism of fatty acids, also reduced vasodilator responses to BK. 5 These results confirm that NO and prostaglandins do not mediate vasodilator responses to BK in the rat heart but suggest a major role for a P450‐dependent mechanism via AA metabolism.