ISSN:
1432-1912
Keywords:
Key words Cerebral arteries
;
Endothelin converting
;
enzyme
;
Endothelin receptors
;
Endothelins
;
Phosphoramidon
;
Vascular endothelium
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The effect of big endothelin-1 (big ET-1) and its conversion to endothelin-1 (ET-1) in rabbit cerebral arteries were examined. Big ET-1 and ET-1 induced concentration-dependent contractions in the basilar artery; ET-1 was approximately 8 times more potent than big ET-1. The metalloprotease inhibitor phosphoramidon (30 μmol/l) almost abolished the contractile response to big ET-1, whereas the ET-1-induced contraction was unaffected. Removal of the endothelium did not attenuate the big ET-1-induced contraction. ET-1 was approximately 14 times more potent than endothelin-3 (ET-3) to elicit contraction. The contractions induced by big ET-1, ET-1 and ET-3 were all inhibited by the ETA receptor antagonist BQ 123 (3 μmol/l). The ETB receptor antagonist IRL 1038 (3 μmol/l) had no effect on the contractile responses to big ET-1 and ET-1, but produced a small inhibition of the ET-3-induced contraction. Formation of ET-1 was demonstrated in membrane fractions of cerebral arteries incubated with big ET-1 as measured by high pressure liquid chromatography followed by radioimmunoassay. These results suggest that externally applied big ET-1 is converted to ET-1 by a phosphoramidon-sensitive “endothelin converting enzyme” present in the vascular smooth muscle cells. The ET-1 formed subsequently mediates the big ET-1-induced contraction by activation of mainly ETA receptors, although a small contribution of ETB receptors cannot be excluded.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00170842
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