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Effect of lovastatin on cerebral circulation in spontaneously hypertensive rats
O Régrigny1, J Atkinson, C Capdeville-Atkinson
1Laboratoire de Pharmacologie Cardiovasculaire, Faculté de Pharmacie, Nancy, France.
Insights
Lovastatin treatment in hypertensive rats reduced arteriolar wall thickness but did not affect cerebral blood flow autoregulation. This suggests statins may alter cerebral vessel structure without impacting critical blood flow regulation mechanisms.
Area of Science:
- Cardiovascular Physiology
- Neurovascular Research
- Pharmacology
Background:
- Statins are commonly prescribed for hypertensive patients and are known to reduce stroke incidence.
- The specific impact of statins on cerebral circulation and autoregulation remains under-investigated.
- Lovastatin has shown potential in reducing hypertension-related renal arteriolar hypertrophy.
Purpose of the Study:
- To investigate the effects of lovastatin on cerebral arteriole structure and mechanics.
- To determine lovastatin's influence on the lower limit of cerebral blood flow (CBF) autoregulation in spontaneously hypertensive rats (SHR).
Main Methods:
- Cerebral blood flow and arteriolar diameter were measured in SHR and Wistar-Kyoto rats (WKY) under baseline and hypotensive conditions.
- Vessel wall cross-sectional area (CSA) and stress-strain relationships were analyzed to assess arteriolar mechanics.
- Lovastatin treatment (20 mg x kg(-1) x d(-1) for 1 month) was administered to a subset of SHR.
Main Results:
- Lovastatin treatment slightly reduced mean arterial pressure and normalized the cross-sectional area (CSA) of cerebral arterioles in SHR.
- Stress-strain analysis indicated that lovastatin attenuated the increase in passive distensibility of cerebral arterioles.
- No significant effect of lovastatin was observed on the external diameter of cerebral arterioles or the lower limit of CBF autoregulation.
Conclusions:
- Lovastatin significantly impacts cerebral arteriolar structure and mechanics, reducing wall CSA and altering passive distensibility.
- Despite these structural changes, lovastatin does not alter the lower limit of cerebral blood flow autoregulation in spontaneously hypertensive rats.
- The lack of effect on CBF autoregulation may be attributed to lovastatin's limited impact on the internal diameter of cerebral arterioles.
Abstract:
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.
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