Identification of a region of rat chromosome 1 that impairs the myogenic response and autoregulation of cerebral blood flow in fawn-hooded hypertensive rats

摘要

This study examined the effects of transfer of a 2.4-Mbp region of rat chromosome 1 (RNO1) from Brown Norway (BN) into fawn-hooded hypertensive (FHH) rats on autoregulation (AR) of cerebral blood flow (CBF) and the myogenic response of middle cerebral arteries (MCAs). AR of CBF was poor in FHH and FHH.1~(BN) AR" congenic strains that excluded the critical 2.4-Mbp region. In contrast, AR was restored in FHH.1~(BN) AR~+ congenic strains that included this region. The diameter of MCAs of FHH rats increased from 140 +- 14 to 157 +- 18 fxm when transmural pressure was increased from 40 to 140 minHg, but it decreased from 137 +- 5 to 94 +- 7 (xm in FHH.1~(BN) AR~+ congenic strains. Transient occlusion of MCAs reduced CBF by 80% in all strains. However, the hyperemic response following ischemia was significantly greater in FHH and AR" rats than that seen in AR~+ congenic strains (AR", 173 +- 11% vs. AR~+, 124 +- 5%). Infarct size and edema formation were also significantly greater in an AR" strain (38.6 +- 2.6 and 12.1 +- 2%) than in AR~+ congenic strains (27.6 +- 1.8 and 6.5 +- 0.9%). These results indicate that there is a gene in the 2.4-Mbp region of RNO1 that alters the development of myogenic tone in cerebral arteries. Transfer of this region from BN to FHH rats restores AR of CBF and vascular reactivity and reduces cerebral injury after transient occlusion and reperfusion of the MCA.cerebral blood flow; middle cerebral artery; autoregulation of CBF; t-MCAO; ischemic stroke