Effects of Endothelin Receptor Inhibition on Cerebral Arterioles in Hypertensive Rats

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Abstract
Abstract The purpose of this study was to examine the effects of endothelin receptor inhibition on cerebral arterioles in stroke-prone spontaneously hypertensive rats (SHRSP). Structure and mechanics of cerebral arterioles were examined in untreated Wistar-Kyoto rats (WKY) and SHRSP that were either untreated or treated for 3 months with bosentan, an inhibitor of endothelin receptors (100 mg/kg per day). We measured pressure, external diameter, and cross-sectional area of the vessel wall (histologically) in maximally dilated (EDTA) arterioles on the cerebrum. Bosentan reduced but did not normalize arteriolar mean pressure (103±3 and 81±5 mm Hg in untreated and treated SHRSP versus 51±4 mm Hg in WKY, P <.05; mean±SEM) and pulse pressure (40±2 and 33±2 mm Hg in untreated and treated SHRSP versus 25±3 mm Hg in WKY, P <.05) in SHRSP. Cross-sectional area of the vessel wall (CSA) was increased in untreated SHRSP (1627±173 μm 2 ), and CSA in treated SHRSP (1287±78 μm 2 ) was similar to that in WKY (1299±65 μm 2 ). Bosentan had no effect on reductions in external diameter (remodeling) of cerebral arterioles (104±7 and 96±4 μm in untreated and treated SHRSP compared with 126±7 μm in WKY, P <.05). Stress-strain curves indicate that bosentan had no significant effect on distensibility of arterioles on the cerebrum in SHRSP. The results suggest that endothelin-1 may contribute to the development of hypertrophy, but not remodeling or changes in distensibility, of cerebral arterioles in SHRSP.