Differences in endothelium-dependent cerebral dilation by bradykinin and acetylcholine.
We compared the mechanism of action of acetylcholine and bradykinin, two agents that cause endothelium-dependent relaxation, on cerebral arterioles of cats equipped with cranial windows for the observation of the cerebral microcirculation. The vasodilation caused by bradykinin was eliminated by cyclooxygenase inhibition with topical indomethacin, it was reduced by topical deferoxamine, an agent that scavenges iron and thereby inhibits the production of hydroxyl radical via the Haber-Weiss reaction, and it was eliminated by 3-amino-1,2,4-triazole, an agent that inhibited superoxide production by cyclooxygenase. The vasodilation from acetylcholine was not affected by these agents. Acetylcholine induced a transferable, short-lived vasodilator material in bioassay experiments, whereas bradykinin did not. Bradykinin or acetylcholine, when applied topically by themselves, induced arteriolar dilation; when applied together, they did not. The findings are consistent with the view that the cerebral arteriolar dilation from bradykinin is caused by oxygen radicals generated in association with accelerated arachidonate metabolism via cyclooxygenase, whereas the dilation from acetylcholine is caused by an endothelium-derived relaxing factor (EDRF) similar to that generated by this agent in large vessels in vitro. The EDRF from acetylcholine and the radicals from bradykinin interact and inactivate each other.
Kontos
H A
HA
Department of Medicine, Medical College of Virginia, Richmond 23298.
Wei
E P
EP
Kukreja
R C
RC
Ellis
E F
EF
Hess
M L
ML
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001285:Atropine / Q000494:pharmacology; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003676:Deferoxamine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D011449:Prostaglandin Endoperoxides / Q000096:biosynthesis; D011453:Prostaglandins / Q000096:biosynthesis; D014664:Vasodilation
D011449:Prostaglandin Endoperoxides; D011453:Prostaglandins; D009569:Nitric Oxide; D001285:Atropine; D003676:Deferoxamine; D000109:Acetylcholine; D001920:Bradykinin; D007213:Indomethacin; D000640:Amitrole