Hydroxyl radical mediates the endothelium-dependent relaxation produced by bradykinin in mouse cerebral arterioles.
Bradykinin relaxes arterioles on the brain's surface. This response is endothelium-dependent. The data presented here confirm the hypothesis that hydroxyl free radical mediates this response and may be the endothelium-dependent relaxing factor for bradykinin in this microvascular bed. The response to a locally applied bolus of bradykinin (80 micrograms/ml) was monitored by intravital TV microscopy. The response was significantly inhibited or totally blocked by the presence of superoxide dismutase 60 U/ml, catalase 46 U/ml, or deferoxamine 0.1 or 0.2 mM. The superoxide dismutase scavenges superoxide radical, which is known to enter the subarachnoid space as a consequence of cyclooxygenase activation. Cyclooxygenase is activated by bradykinin. The superoxide can form H2O2, scavenged by catalase, and the two together generate hydroxyl. The formation of hydroxyl radical is catalyzed by iron. Deferoxamine 0.1 mM scavenges the iron, blocking the generation of hydroxyl. Deferoxamine 0.2 mM also directly scavenges the hydroxyl. None of the pharmacologic probes had an effect on arteriolar diameter when locally applied without bradykinin. Since the dilation produced by bradykinin was inhibited or totally blocked by probes that prevented hydroxyl formation or directly scavenged hydroxyl radical, that radical is either an essential mediator of the arteriolar relaxation, or is the endothelium-dependent relaxing factor for bradykinin in pial arterioles.
Rosenblum
W I
WI
Department of Pathology (Neuropathology), Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000502:physiology*; D005609:Free Radicals; D006878:Hydroxides / Q000494:pharmacology; D017665:Hydroxyl Radical; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction; D009126:Muscle Relaxation
D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; D001920:Bradykinin