Role of extracellular Ca2+ in subarachnoid hemorrhage-induced spasm of the rabbit basilar artery.
OBJECTIVE
The role of extracellular Ca2+ in the maintenance of chronic vasospasm after subarachnoid hemorrhage (SAH) is largely unknown. Indeed, studies thus far have been limited to demonstrations that L-type Ca(2+)-channel antagonists were unable to reverse the spasm. This study tested whether SAH-induced vasospasm is maintained, at least in part. through the influx of extracellular Ca2+ and whether the influx of extracellular Ca2+ occurs through L-type Ca2+ channels and possibly, in addition, through store operated channels (SOCs). Furthermore, as there is considerable evidence in the literature to suggest that the spasm is mediated through endothelin-1 (ET-1) release, we tested whether the Ca2+ dependency of the spasm was consistent with the mediation of the spasm by ET-1.


METHODS
Chronic spasm of the basilar artery was induced in a double SAH rabbit model. Relaxation of SAH-, ET-1-, serotonin-, and KC1-constricted basilar artery in response to Ca(2+)-free solution, verapamil, and Ni2+ was measured in situ with the use of a cranial window.


RESULTS
SAH induced 23% constriction of the basilar artery. Ca(2+)-free solution and 1 mumol/L verapamil reversed the constriction of SAH vessels by 60% and 17%, respectively. In contrast, control vessels challenged with 40 to 50 mmol/L KCl, which induced 34% constriction, relaxed in response to Ca(2+)-free solution and verapamil by 98% and 89%, respectively. In SAH vessels, verapamil followed by 0.1 mmol/L Ni2+, which is known to block SOCs, induced a combined relaxation of 67%. Control vessels challenged with 3 nmol/L ET-1, which induced a magnitude of constriction similar to that of SAH (29%), relaxed in response to Ca(2+)-free solution, verapamil, and verapamil plus Ni2+ by 69%, 20%, and 50%, respectively (P > .05) versus respective values in SAH vessels). In contrast, control vessels challenged with 2 to 8 mumol/L serotonin, which induced a magnitude of constriction similar to those of SAH and ET-1 (22%), completely relaxed in response to Ca(2+)-free solution and verapamil.


CONCLUSIONS
These results demonstrate that the maintenance of chronic spasm in the two-hemorrhage rabbit model after SAH is due to smooth muscle cell contractile mechanisms partly dependent on the influx of extracellular Ca2+. The influx of extracellular Ca2+ results from the opening of L-type Ca2+ channels and an additional channel or channels. We speculate that the L-type Ca2+ channel-independent influx of extracellular Ca2+ results from the opening of SOCs. The Ca(2+)-dependent characteristics of the spasm likely reflect the mediation of the spasm by ET-1.
Zuccarello
M
M
Department of Neurosurgery, University of Cincinnati College of Medicine, Ohio 45267-0575, USA.
Boccaletti
R
R
Tosun
M
M
Rapoport
R M
RM
D000818:Animals; D001488:Basilar Artery / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism*; D008297:Male; D009532:Nickel / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D012996:Solutions; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D019332:Endothelin-1; D012996:Solutions; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D012701:Serotonin; D011189:Potassium Chloride; D009532:Nickel; D014700:Verapamil; D002118:Calcium