Angiotensin II induces endothelium-dependent vasodilation of rat cerebral arterioles.
We evaluated the response of cerebral arterioles to angiotensin II (ANG II) in anesthetized rats equipped with a closed cranial window. Topical application of 10(-10)-10(-5) M ANG II induced dose-dependent arteriolar vasodilation. Maximum vasodilation of 24 +/- 2.2% (+/- SE) was attained at a concentration of 10(-6) M ANG II. The dilation in response to ANG II was blocked by 3 micrograms/ml indomethacin, a cyclooxygenase inhibitor, and was reversed to minimal vasoconstriction by 10(-5) M methylene blue, a substance that has been reported to eliminate endothelium-dependent vasodilation. Coapplication of indomethacin with methylene blue reduced the arteriolar response to ANG II to a similar extent as the application of indomethacin alone. Indomethacin or methylene blue did not inhibit the vasodilation induced by 10(-5) M adenosine, which is not endothelium and cyclooxygenase dependent. Mercury light illumination of the pial vessels after intravenous injection of fluorescein dye, a technique that has been used by others to functionally damage endothelial cells, reversed ANG II (10(-6) M)-induced vasodilation into a -14.2 +/- 2.3% constriction while not affecting the response to adenosine. Our data suggest that ANG II produces vasodilator responses of rat cerebral arterioles by the release of a factor that is derived from the endothelium and may be generated through a cyclooxygenase-dependent mechanism.
Haberl
R L
RL
Department of Neurology, University of Munich, Federal Republic of Germany.
Anneser
F
F
Villringer
A
A
Einhäupl
K M
KM
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D019793:Fluorescein; D005452:Fluoresceins / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008027:Light; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects / Q000528:radiation effects
D005452:Fluoresceins; D000804:Angiotensin II; D008751:Methylene Blue; D019793:Fluorescein; D007213:Indomethacin