Effect of lovastatin on cerebral circulation in spontaneously hypertensive rats.
Statins, which are often given to hypertensive patients, reduce the incidence of stroke. However, their effects on the cerebral circulation have been scarcely studied, although lovastatin has been reported to reduce hypertension-induced renal arteriolar hypertrophy. We examined the structure and mechanics of cerebral arterioles and the lower limit of cerebral blood flow (CBF) autoregulation in spontaneously hypertensive rats (SHR) that were untreated (n=9) or treated for 1 month with lovastatin (n=12; 20 mg x kg(-1) x d(-1)) and in untreated Wistar-Kyoto rats (WKY; n=8). We studied the lower limit of CBF autoregulation by repeated measurement of CBF (arbitrary units; laser Doppler) and internal arteriolar diameter (microm; cranial window) at baseline and during stepwise hypotension. Stress-strain relationships were calculated from repeated measurement of internal arteriolar diameter during stepwise hypotension and cross-sectional area (CSA) of the vessel wall in maximally dilated cerebral arterioles (EDTA, 67 mmol/L). Lovastatin slightly reduced mean arterial pressure (treated, 153+/-3 versus untreated, 171+/-5 mm Hg, P<0.05; WKY, 106+/-3 mm Hg) and normalized CSA (treated, 826+/-52 versus untreated, 1099+/-16 microm(2), P<0. 05; WKY, 774+/-28 microm(2)). Stress-strain curves show that lovastatin also attenuated the increase in passive distensibility. Lovastatin had no effect on the external diameter of cerebral arterioles or the lower limit of CBF autoregulation. Our results show that although lovastatin has substantial effects on arteriolar mechanics and wall CSA, it has little effect on internal diameter. This phenomenon may explain its lack of effect on CBF autoregulation.
Régrigny
O
O
Laboratoire de Pharmacologie Cardiovasculaire, Faculté de Pharmacie, Nancy, France.
Atkinson
J
J
Capdeville-Atkinson
C
C
Limiñana
P
P
Chillon
J M
JM
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology*; D008148:Lovastatin / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000924:Anticholesteremic Agents; D008148:Lovastatin