Characterization of the potent combined endothelin(A/B)-antagonist PD 142893 on cerebral vessels.

A disturbed balance between endothelin (ET)-1 and nitric oxide (NO) seems to play a key role in the development of delayed cerebral vasospasm following subarachnoidal hemorrhage. Therefore, the effect of PD 142893 one of the first potent ET(A)- and ET(B)-receptor antagonists was characterized on the contraction and relaxation induced by ET-1 and bigET-1 on rat basilar artery (BA). Concentration-effect curves (CECs) were constructed by cumulative application of ET-1 or big ET-1 on BA ring segments with (E+) and without (E-) functionally intact endothelium.

Cerebrovascular characterization of the novel nonpeptide endothelin-A receptor antagonist LU 208075.

Enhanced cerebrovascular resistance under pathologic conditions, like cerebral vasospasm after subarachnoid hemorrhage, seems to be caused by the vasocontractile effect of endothelin-1 (ET-1). Therefore, the effect of the novel and ET(A) receptor selective antagonist LU 208075 was characterized by the contraction and relaxation induced by ET-1 and bigET-1 on rat basilar artery. Basilar artery ring segments with (E+) and without (E-) functionally intact endothelium were prepared to measure the isometric force.

Effect of the novel endothelin(A) receptor antagonist LU 208075 on contraction and relaxation of isolated rat basilar artery.

Increased levels of endothelin (ET)-1 and bigET-1 may be responsible for enhanced cerebroarterial resistance under pathologic conditions. Therefore, the effect of LU 208075, a novel ET(A)-selective receptor antagonist was determined. The aim of the study was to investigate in vitro the inhibitory effect of LU 208075 on ET-1 and bigET-1 induced contraction and relaxation in rat basilar artery segments.