Evidence for a possible role of the brain kallikrein-kinin system in the modulation of the cerebral circulation.
Experiments by others have shown that exogenous bradykinin dilates cerebral arterioles and that the brain contains kininogen and kallikrein, the latter being the enzyme which converts kininogen to bradykinin. The objective of these experiments was to determine if bradykinin produced from endogenous brain kininogen can affect the cerebral microcirculation. Rabbit pial arteriolar diameter was measured with a microscope using the closed cranial window technique. Topical application of bradykinin (10(-8)-10(-5) M) induced a dose-dependent vasodilation (8-46%) which was completely inhibited by the cyclooxygenase enzyme inhibitors indomethacin and meclofenamic acid. Topical application of 1 U of tissue kallikrein per milliliter of artificial cerebrospinal fluid induced 43% dilation, which could be prevented by local treatment with indomethacin or the proteinase inhibitor aprotinin. The action of aprotinin and indomethacin was specific, since aprotinin did not affect the dilation produced by bradykinin, and indomethacin did not affect dilation produced by adenosine. A second application of kallikrein had no effect on cerebral diameter, yet the arterioles still responded normally to exogenous bradykinin, indicating that the first application of kallikrein depleted brain kininogen. We suggest that activation of brain kallikrein and subsequent formation of kinin from brain kininogen may be important in modulation of cerebral blood flow or generation of cerebral edema.
T
T
Kamitani
M H
MH
Little
E F
EF
Ellis
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001160:Arterioles / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology / Q000502:physiology*; D002560:Cerebrovascular Circulation; D016861:Cyclooxygenase Inhibitors; D007213:Indomethacin / Q000494:pharmacology; D007610:Kallikreins / Q000494:pharmacology / Q000502:physiology*; D007704:Kininogens / Q000378:metabolism; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D007704:Kininogens; D008469:Meclofenamic Acid; D007611:Aprotinin; D007610:Kallikreins; D001920:Bradykinin; D007213:Indomethacin