Prevention by the new Ca2+ channel antagonist, AJ-3941, of loss of endothelium-dependent relaxation after subarachnoid hemorrhage in rats.

Abstract

AJ-3941 ((+/-)-(E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]-oxepine-11-yl ) -4-(3-phenyl-2-propenyl)-piperazine dimaleate; CAS No. 143110-70-7), a cerebrovascular-selective Ca2+ channel antagonist having anti-lipid peroxidative action, was reported to prevent cerebral vasospasm following subarachnoid hemorrhage in rats. The present study was undertaken to determine whether AJ-3941 protects the impairment of cerebroarterial endothelium-dependent relaxation which is concomitantly induced with cerebral vasospasm. Subarachnoid hemorrhage biphasically suppressed the response to acetylcholine in rat basilar artery, at 0.5 h (n = 4; P < 0.06) and 1 day (n = 5; P < 0.05) after subarachnoid hemorrhage. The reduction of the responses was correlated significantly to the degree of vasospasm determined angiographically. This reduction was accompanied by a 49% increase of arterial lipid peroxide contents. Endothelium-independent relaxation in subarachnoid hemorrhage rats was preserved in response to 3-morpholinosydnonimine, sodium nitroprusside and papaverine. AJ-3941 prevented (n = 6-8, P < 0.05) the suppression of the acetylcholine-induced response and the increase in lipid peroxide content in subarachnoid hemorrhage rats. These results suggest that AJ-3941 could exert its vasospasmolytic effect by preserving endothelial function through its anti-lipid peroxidative action, in addition to its inhibition of vasospasmogen-induced vasoconstriction related to intracellular Ca2+ mobilization.

• Authors: H Minato, Y Honda, Y Masuda, B Fujitani, K Hosoki
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 315 Issue 3 Pg. 297-303 (Nov 21 1996) ISSN: 0014-2999 [Print] Netherlands
• PMID: 8982668 (Publication Type: Journal Article)

Chemical References

• Calcium Channel Blockers
• Dibenzoxepins
• Piperazines
• AJ 3941
• Acetylcholine

Topics

• Acetylcholine (pharmacology)
• Animals
• Calcium Channel Blockers (pharmacology)
• Dibenzoxepins (pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Male
• Muscle Relaxation (drug effects)
• Piperazines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Subarachnoid Hemorrhage (drug therapy)