The position of NO among endogenous vasodilators.
Bradykinin stimulates phospholipases to release arachidonic acid (AA) which can be metabolized by cyclooxygenase, lipoxygenase and cytochrome P450 (P450) to yield vasoactive products that may contribute to the effect of the peptide. In the rat kidney, pharmacological evidence suggests that a substantial component of the vasodilator response is dependent on P450-AA metabolism. In the heart, the vasodilator response to bradykinin is independent of NO and prostaglandins but reduced by inhibitors of P450, including 17-ODYA, an inhibitor of fatty acid metabolism, also suggesting a role of P450-AA. Moreover, the renal and coronary vasodilator responses to bradykinin are associated with release of P450-AA products measured by gas chromatography-mass spectrometry (GC-MS). The coronary vasodilator response to bradykinin is also dependent on activation of K+ channels linking P450-AA and hyperpolarization. Formation of vasodilator eicosanoids derived via the P450 pathway may make important contributions to the control of vascular tone, local blood flow and, thereby, blood pressure.
Quilley
J
J
Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
Fulton
D
D
McGiff
J C
JC
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology*
D015221:Potassium Channels; D016718:Arachidonic Acid; D009569:Nitric Oxide; D003577:Cytochrome P-450 Enzyme System; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine; D001920:Bradykinin