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 mm Hg in WKY, P < .05) in SHRSP. Cross-sectional area of the vessel wall (CSA) was increased in untreated SHRSP (1627 +/- 173 microm2), and CSA in treated SHRSP (1287 +/- 78 microm2) was similar to that in WKY (1299 +/- 65 microm2). Bosentan had no effect on reductions in external diameter (remodeling) of cerebral arterioles (104 +/- 7 and 96 +/- 4 microm in untreated and treated SHRSP compared with 126 +/- 7 microm 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.