Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Zimmermann, M. et al.

Zimmermann, Vatter, Weyrauch, Lange, Krishnan, Raabe, Seifert,

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. The effect of PD 142893 was determined by the modified pK(b) value and the shift between the CECs. PD 142893 inhibited the contraction by ET-1 and bigET-1. The pK(b)-values were for ET-1: 5.17 (E+) and 5.15 (E-) and for big ET-1: 5.34 (E+) and 5.57 (E-), respectively. A significant relaxation of pre-contracted segments by ET-1 or big ET-1 was neither observed in the presence nor in the absence of the receptor antagonist. The present data suggest a competitive inhibition of the ET(A)-receptor mediated contraction of cerebral arteries by PD 142893. The ET(B)-dependent relaxation of the cerebrovasculature is inhibited by PD 142893 at least in a comparable amount of contraction.[1]

References

Characterization of the potent combined endothelin(A/B)-antagonist PD 142893 on cerebral vessels. Zimmermann, M., Vatter, H., Weyrauch, E., Lange, B.N., Krishnan, R., Raabe, A., Seifert, V. Neurol. Res. (2004) [Pubmed]

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