Inhibition of endothelin-converting enzyme activity in the rabbit basilar artery.
OBJECTIVE
Endothelin (ET)-1 may be involved in the regulation of cerebrovascular resistance under pathological conditions, most notably during the development of vasospasm after subarachnoid hemorrhage. Blocking ET-converting enzyme activity may be a promising approach to the prevention of cerebral vasospasm after subarachnoid hemorrhage.


METHODS
In this study, the effects of several putative ET-converting enzyme inhibitors were investigated after intracisternal application in rabbits, to inhibit basilar artery contractions induced by big ET-1 (2 x 10(-6) mol/L).


RESULTS
In the group pretreated with [D-Val22]big ET-1[16-38] (2 x 10(-5) mol/L) (n = 8), the angiographically measured diameter of the basilar artery changed from 0.63 +/- 0.12 mm to 0.66 +/- 0.12 mm. In the control group (n = 8), the diameter of the basilar artery decreased from 0.71 +/- 0.13 mm to 0.57 +/- 0.15 mm. These results corresponded to an increase in vessel diameter of 5 +/- 10% in the treatment group and a decrease in vessel diameter of 20 +/- 16% in the control group (P = 0.014). In the group pretreated with captopril (2 x 10(-4) mol/L) (n = 8), the angiographically measured diameter of the basilar artery changed from 0.64 +/- 0.11 mm to 0.71 +/- 0.10 mm. These results corresponded to an increase in vessel diameter of 14 +/- 19% in the treatment group, compared with a decrease in vessel diameter of 20 +/- 16% in the control group (P = 0.014).


CONCLUSIONS
These results demonstrate that [D-Val22]big ET-1[16-38] and captopril act as highly potent ET-converting enzyme inhibitors, affecting big ET-1-induced contraction of the rabbit basilar artery.
Zimmermann
M
M
Neurosurgical Clinic, Johann Wolfgang Goethe University, Frankfurt, Germany. Michael.Zimmermann@em.uni-frankfurt.de
Jung
C
C
Raabe
A
A
Spanehl
O
O
Fach
K
K
Seifert
V
V
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D001488:Basilar Artery / Q000201:enzymology*; D002216:Captopril / Q000494:pharmacology; D002533:Cerebral Angiography; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008666:Metalloendopeptidases; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000201:enzymology*; D014664:Vasodilation / Q000187:drug effects; D020301:Vasospasm, Intracranial / Q000201:enzymology*
D016232:Endothelins; D004791:Enzyme Inhibitors; C089858:big endothelin-1(16-38), valine(22)-; D002216:Captopril; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes