Objective: To investigate the expression of endothelin (ET)-1 and its receptors in the cerebral arterioles of stroke-prone (spSHR) and control spontaneously hypertensive rats (SHRs) and the changes in endothelin receptor subtypes A and B density elicited by a stroke-permissive diet, before the development of stroke.
Methods: Six-week-old SHRs (n = 11) and spSHRs (n = 11) were assigned to either a regular or a 'Japanese'-style diet, in addition to 1% NaCl in the drinking water, for 4 weeks. Cryosections (10 μm thick) of rat brain were assessed for endothelin receptor distribution and density by autoradiography with [125I]ET-1 (10-10 mol/l) in the presence of cold ET-1 (10-6 mol/l) or the peptide antagonists BQ-123 (10-6 mol/l) or BQ-788 (10-6 mol/l). Reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry were used to detect specific mRNAs and localize immunoreactive ET-1 and ETA and ETB.
Results: In both strains, immunoreactive ET-1 was detected in the endothelium of cerebral arterioles, and RT-PCR and autoradiography demonstrated the coexistence of both receptor subtypes in brain homogenates and the cerebral arteriole walls, respectively. With the regular diet, the ETA receptor density was lower in SHRs than in spSHRs (P = 0.007), whereas the ETB receptor density was similar (P = NS). The Japanese-style diet increased the density of ETA receptors (P = 0.006) in SHRs, but decreased it (P = 0.019) in spSHRs. No effect was seen on ETB receptor density.
Conclusions: ETA and ETB receptor subtypes are expressed in the wall of cerebral arterioles of SHRs and spSHRs. The latter strain showed a marked increase in ETA receptor density under a regular diet, in addition to an altered regulation in response to a stroke-permissive diet.