Captopril improves cerebrovascular structure and function in old hypertensive rats


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Abstract

We examined the effects of an angiotensin-converting enzyme inhibitor (ACEI), captopril, on cerebral arterioles in young and old spontaneously hypertensive rats (SHR).Animals were anesthetized with sodium pentobarbitone (60 mg kg−1 day−1). We measured cerebral blood flow (CBF, arbitrary units) and cerebral arteriolar internal diameter (ID, μm) prior to and during stepwise hypotension (SH) in 6- (WKY-6) and 15-month-old (WKY-15) Wistar Kyoto rats and in age-matched SHR that were untreated (SHR-6 and SHR-15) or treated for 3 months with captopril (SHR-6C, 105±2 mg kg−1 day−1 and SHR-15C, 94±1 mg kg−1 day−1). ID and cross-sectional area of the vessel wall (CSA) were measured in deactivated (EDTA) cerebral arterioles during a second SH.Captopril decreased the lower limit of CBF autoregulation (61±6 in SHR-6C and 51±2 in SHR-15C versus 52±6 in WKY-6 and 62±7 in WKY-15 and 83±14 mmHg in SHR-6 and 120±19 mmHg in SHR-15; P<0.05) and CSA (510±21 in SHR-6C and 585±25 in SHR-15C versus 529±12 in WKY-6 and 549±20 in WKY-15 and 644±38 mmHg in SHR-6 and 704±38 mmHg in SHR-15; P<0.05).Captopril increased cerebral arteriolar external diameter of SHR (105±5 in SHR-6C and 94±4 in SHR-15C vs 125±8 in WKY-6 and 108±3 in WKY-15 and 83±2 mmHg in SHR-6 and 80±2 mmHg in SHR-15 for a pial arteriolar pressure step of 35–39 mmHg; P<0.05). Captopril attenuated increases in cerebral arteriolar distensibility in young SHR.Thus, ACEIs attenuate eutrophic and hypertrophic inward remodeling of cerebral arterioles in young and old SHR, thus decreasing the lower limit of CBF autoregulation.British Journal of Pharmacology (2005) 144, 349–356. doi:10.1038/sj.bjp.0706001

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