Angiotensin degradation products mediate endothelium-dependent dilation of rabbit brain arterioles.
This study demonstrates that the hexapeptide angiotensin II-(3-8) and L-arginine, generated through enzymatic degradation of angiotensin, mediate endothelium-dependent dilation in rabbit brain arterioles. Topical application of angiotensin II (10(-5) M) on the brain surface of anesthetized rabbits caused 21.6 +/- 4.5% (mean +/- SEM) cerebral arteriolar dilation. The cyclooxygenase inhibitor indomethacin did not change this dilation. The natural degradation product of angiotensin II in the brain, angiotensin III, also induced vasodilation at concentrations of 10(-7) to 10(-5) M. The dilation to angiotensin II and angiotensin III was eliminated in the presence of 10(-5) M methylene blue, a known inhibitor of endothelium-dependent vasodilation. Amastatin, an aminopeptidase inhibitor and blocker of enzymatic angiotensin degradation, also inhibited the response to angiotensin II and angiotensin III. The angiotensin fragment angiotensin II-(3-8), which lacks the amino-terminal L-arginine residue of angiotensin III, did not elicit an arteriolar response. When angiotensin II-(3-8) was topically applied subsequent to L-arginine, a 21.2 +/- 2.9% vasodilation was observed. L-Arginine itself induced only moderate vasodilation with a maximum of 4.0 +/- 0.9% at 10(-5) M L-arginine. The dilating response to angiotensin II-(3-8) after L-arginine was inhibited by methylene blue. It was not affected by amastatin. It is concluded that degradation products of angiotensin, rather than angiotensin II itself, induce endothelium-dependent dilation in rabbit brain arterioles without involvement of cyclooxygenase products.(ABSTRACT TRUNCATED AT 250 WORDS)
Haberl
R L
RL
Department of Neurology, University of Munich, FRG.
Decker
P J
PJ
Einhäupl
K M
KM
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000805:Angiotensin III / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000502:physiology; D002560:Cerebrovascular Circulation; D004730:Endothelium, Vascular / Q000502:physiology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply; D011817:Rabbits; D014664:Vasodilation
D010446:Peptide Fragments; D000804:Angiotensin II; D000805:Angiotensin III