Alterations in autoregulatory and myogenic function in the cerebrovasculature of Dahl salt-sensitive rats.
OBJECTIVE
Dahl salt-sensitive rats fed an 8.7% NaCl diet exhibited hypertensive encephalopathy and developed seizures associated with areas of blood-brain barrier (BBB) disruption without brain ischemia. The incidence of hemorrhagic stroke was low (7/47). We tested the hypothesis that a defect in cerebral blood flow (CBF) autoregulation under hypertensive conditions preceded hypertensive encephalopathy.


METHODS
Brain ischemia and BBB disruption were assessed with the use of tetrazolium red staining and Evans blue dye extravasation, respectively. Myogenic constriction to pressure was measured in isolated middle cerebral arteries (MCAs) with a pressure myograph. CBF autoregulation was assessed with the use of laser-Doppler techniques.


RESULTS
Asymptomatic rats fed 8.7% NaCl had MCAs that developed an age-related attenuation in their ability to constrict to pressure, which was amplified in rats exhibiting hypertensive encephalopathy. The MCAs of rats with hemorrhagic stroke lost this function and developed large degrees of basal tone. The majority (4/6) of asymptomatic rats fed high salt for longer than 3 weeks exhibited a linear relationship between CBF and blood pressure. The characteristics of CBF regulation were consistent with the possible absence of autoregulation coupled with cerebrovascular vasoconstriction.


CONCLUSIONS
Both MCA pressure-dependent constriction and CBF autoregulation in the MCA perfusion domain were lost before the development of hypertensive encephalopathy or hemorrhagic stroke. These defects could contribute to the development of BBB disruption during hypertension. Cerebrovascular vasoconstriction in the absence of CBF autoregulation may protect the brain from excessive overperfusion during hypertension and could account for the low incidence of cerebral hemorrhage in this model.
Division of Basic Medical Sciences, Memorial University, Health Science Center, St John's, Newfoundland, Canada A1B 3V6. jsmeda@mun.ca
John S
JS
Smeda
Geoffrey W
GW
Payne
D000367:Age Factors; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004396:Coloring Agents; D004195:Disease Models, Animal; D018450:Disease Progression; D006706:Homeostasis / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D020343:Hypertensive Encephalopathy / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D017078:Laser-Doppler Flowmetry; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000503:physiopathology*; D009213:Myography; D051381:Rats; D020303:Rats, Inbred Dahl; D012982:Sodium, Dietary / Q000494:pharmacology; D015996:Survival Rate; D014661:Vasoconstriction / Q000187:drug effects
D004396:Coloring Agents; D012982:Sodium, Dietary