Effects of endothelin receptor inhibition on cerebral arterioles in hypertensive rats

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 mmHg in WKY, P<.05) in SHRSP. Cross-sectional area of the vessel wall (CSA) was increased in untreated SHRSP (1627+/-173 mu m(2)), and CSA in treated SHRSP (12871+/-78 mu m(2)) was similar to that in WKY (1299+/-65 mu m(2)). Bosentan had no effect on reductions in external diameter (remodeling) of cerebral arterioles (104+/-7 and 96+/-4 mu m in untreated and treated SHRSP compared with 126+/-7 mu m 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.