Prevention of stroke and preservation of the functions of cerebral arteries by treatment with perindopril in stroke-prone spontaneously hypertensive rats.
The aim of this study was to determine whether the prevention of stroke with perindopril treatment in stroke-prone spontaneously hypertensive rats (SHRSP) is associated with the preservation of the myogenic properties of the cerebral arteries. After weaning at 4 weeks of age, male SHRSP were fed a Japanese-style rat diet with high salt to induce stroke development. Treatment with perindopril was given by gavage every morning beginning at 6 weeks of age. There were three experimental groups: two groups treated with 4 mg.kg-1.day-1 perindopril for different durations (8 or 12 weeks) and one control group consisting of littermates given distilled water. All the control animals developed stroke and died within 14 weeks of age, and myogenic response of the middle cerebral arteries (MCA) to pressure increase was lost in these animals. In contrast, all the treated SHRSP survived during the treatment period, and myogenic response of the MCA was preserved. After withdrawal of the treatment, SHRSP treated for a longer period (12 weeks) also survived longer than those treated for a shorter period (8 weeks). The subsequent development of stroke and death following treatment withdrawal after 8 or 12 weeks of treatment was associated with the loss of pressure-dependent constriction in MCA. A longer treatment duration also increased the stiffness of the MCA, MCA from SHRSP after 12 weeks of treatment had smaller external and lumen diameters, and thicker walls than those from the 8-week treatment group. In a separate study, we found that treatment of SHRSP with 1 or 4 mg.kg-1.day-1 of perindopril for 24 weeks beginning at 6 weeks of age also protected them against death related to stroke, because these rats survived up to 43 weeks of age, when the experiment was terminated. We conclude that there is an association between the absence of myogenic response in cerebral arteries and stroke development in SHRSP. Perindopril treatment preserves the myogenic response of MCA in SHRSP and prevents the stroke development in these animals. A prolonged treatment could increase the survival of SHRSP through a remodelling of the MCA and increasing the stiffness of the cerebral arteries.
Wang
H
H
Smooth Muscle Research Programme, McMaster University, Hamilton, ON, Canada.
Smeda
J S
JS
Lee
R M
RM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002536:Cerebral Arteries / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000503:physiopathology / Q000517:prevention & control*; D006984:Hypertrophy; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D020913:Perindopril; D011312:Pressure; D051381:Rats; D011918:Rats, Inbred SHR; D013314:Stress, Mechanical; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D020913:Perindopril