{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T18:31:18Z","timestamp":1774981878519,"version":"3.50.1"},"reference-count":34,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,6]]},"abstract":"<jats:p content-type=\"fine-print\"><jats:italic>Object.<\/jats:italic> The disturbed balance between nitric oxide and endothelin (ET)\u20141 in the cerebrovasculature seems to play a major role in the development of cerebral vasospasm after subarachnoid hemorrhage. Endothelin-1 represents the contractile part in this balance. In addition to the prevailing ET<jats:sub>A<\/jats:sub> receptor\u2014dependent contractile effect, ET-1 also has ET<jats:sub>B<\/jats:sub> receptor\u2014mediated vasodilatory attributes. The aim of the present study was to define the actual selectivity of clazosentan, the first putative highly ET<jats:sub>A<\/jats:sub> receptor\u2014selective antagonist clinically proven to be effective in the treatment of vasospasm in the cerebrovasculature.<\/jats:p>\n<jats:p content-type=\"fine-print\"><jats:italic>Methods.<\/jats:italic> Rat basilar artery ring segments with endothelial function were used for the measurement of isometric force. Concentration effect curves were constructed by cumulative application of sarafotoxin S6c, ET-1, or big ET-1 in the presence or absence of clazosentan (10<jats:sup>\u22129<\/jats:sup> to 10<jats:sup>\u22126<\/jats:sup> M) after a precontraction was induced by prostaglandin F<jats:sub>2\u03b1<\/jats:sub>. The inhibition by clazosentan was estimated by the value of the affinity constant (pA<jats:sub>2<\/jats:sub>).<\/jats:p>\n<jats:p content-type=\"fine-print\">The relaxation induced by sarafotoxin S6c, ET-1, and big ET-1 was inhibited in a competitive manner by clazosentan, yielding pA<jats:sub>2<\/jats:sub> values of 7.1, 6.7, and 6.5, respectively. The selectivity to the ET<jats:sub>A<\/jats:sub> receptor in the cerebrovascular system was approximately two logarithmic units.<\/jats:p>\n<jats:p content-type=\"fine-print\"><jats:italic>Conclusions.<\/jats:italic> The present investigation shows a competitive inhibition of ET<jats:sub>B<\/jats:sub> receptor\u2014mediated relaxation in cerebral vessels by clazosentan in therapeutically relevant concentrations. Thus, additional clinical trials should be undertaken to evaluate clazosentan concentrations in cerebrospinal fluid. Furthermore, the present data may be taken to describe the pharmacological properties for an ET receptor antagonist specifically tailored for the treatment of pathological conditions of impaired cerebral blood flow.<\/jats:p>","DOI":"10.3171\/jns.2005.102.6.1108","type":"journal-article","created":{"date-parts":[[2009,5,13]],"date-time":"2009-05-13T18:04:03Z","timestamp":1242237843000},"page":"1108-1114","source":"Crossref","is-referenced-by-count":32,"title":["Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist shown to be clinically effective for the treatment of cerebral vasospasm. Part II: Effect on endothelinB receptor\u2014mediated 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