Stroke development in stroke-prone spontaneously hypertensive rats alters the ability of cerebrovascular muscle to utilize internal Ca2+ to elicit constriction.
OBJECTIVE
The ability of middle cerebral arteries (MCAs) to utilize intracellular smooth muscle (SM) Ca2+ to produce constriction in response to pressure and agonists was assessed in relation to hemorrhagic stroke development in Wistar-Kyoto stroke-prone (SHRSP) and stroke-resistant (srSHR) spontaneously hypertensive rats.


METHODS
MCAs were studied with the use of a pressure myograph at 100 mm Hg.


RESULTS
MCAs from srSHR and prestroke SHRSP exhibited pressure-dependent constriction and constricted in response to vasopressin or serotonin in the presence of nifedipine or the absence of [Ca2+]o. MCAs from poststroke SHRSP lost the latter functions and could only constrict in response to vasopressin/serotonin in Krebs' solution containing Ca2+ in the absence of nifedipine. This indicated that the SM could not utilize internal Ca2+ for constriction and maintained constriction by Ca2+ entry through L-type channels. The MCAs of poststroke SHRSP could not constrict to [K+]o-induced depolarization, suggesting that the agonist-induced opening of the L-type channels occurred by mechanisms other than SM depolarization. Depletion of the sarcoplasmic SM Ca2+ stores of MCAs from srSHR with cyclopiazonic acid did not prevent pressure-dependent constriction.


CONCLUSIONS
Stroke in SHRSP produced a defect in the ability of MCAs to constrict in response to vasopressin or serotonin via the use of an intracellular source of Ca2+. This could be promoted by an inability of the SM to release intracellular Ca2+, by the depletion of internal Ca2+ stores, or by a decrease in the contractile sensitivity to Ca2+ released from the internal stores.
Smeda
John S
JS
Division of Basic Medical Sciences, Room H4354, Memorial University, Health Science Center, St John's, Newfoundland, Canada A1B 3V6. jsmeda@mun.ca
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D066298:In Vitro Techniques; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D009213:Myography; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012701:Serotonin / Q000494:pharmacology; D012982:Sodium, Dietary / Q000494:pharmacology; D020521:Stroke / Q000209:etiology / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D012982:Sodium, Dietary; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D012701:Serotonin; D009543:Nifedipine; D011188:Potassium; D002118:Calcium