A 3-Mbp fragment on rat chromosome 1 affects susceptibility both to stroke and kidney injury under salt loading in the stroke-prone spontaneously hypertensive rat: a genetic approach using multiple congenic strains.

We have previously reported that a major quantitative trait locus (QTL) responsible for susceptibility to salt-induced stroke in the stroke-prone spontaneously hypertensive rat (SHRSP) is located in a 3-Mbp region on chromosome 1 covered by SHRSP.SHR-(D1Rat23-D1Rat213)/Izm (termed Pr1.31), a congenic strain with segments from SHRSP/Izm introduced into the stroke-resistant SHR/Izm. Here, we attempted to narrow down the candidate region on chromosome 1 further through analyses of subcongenic strains constructed for the target region. Simultaneously, salt-induced kidney injury was evaluated through the measurement of urinary albumin and the gene expression of renal tubular injury markers (Kim-1 and Clu) to explore a possible mechanism leading to the onset of stroke. All subcongenic strains examined in this study showed lower susceptibility to salt-induced stroke than SHRSP. Interestingly, Pr1.31 had the lowest stroke susceptibility when compared with newly constructed subcongenic strains harboring fragments of the congenic sequence in Pr1.31. Although Kim-1 and Clu expression after 1 week of salt loading in Pr1.31 did not differ significantly from those in SHRSP, the urinary albumin level of Pr1.31 was significantly lower than those of the other subcongenic strains and that of SHRSP. The present results indicated that, although the congenic fragment in Pr1.31 harbored the gene(s) related to salt-induced organ damages, further genetic dissection of the candidate region was difficult due to multiple QTLs suggested in this region. Further analysis using Pr1.31 will unveil genetic and pathophysiological mechanisms underlying salt-induced end organ damages in SHRSP.

Involvement of Rho GTPases and their regulators in the pathogenesis of hypertension.

Proper regulation of arterial blood pressure is essential to allow permanent adjustment of nutrient and oxygen supply to organs and tissues according to their need. This is achieved through highly coordinated regulation processes controlling vascular resistance through modulation of arterial smooth muscle contraction, cardiac output, and kidney function. Members of the Rho family of small GTPases, in particular RhoA and Rac1, have been identified as key signaling molecules playing important roles in several different steps of these regulatory processes. Here, we review the current state of knowledge regarding the involvement of Rho GTPase signaling in the control of blood pressure and the pathogenesis of hypertension. We describe how knockout models in mouse, genetic, and pharmacological studies in human have been useful to address this question.

Protective effects of fenazinel dihydrochloride against stroke in stroke-prone spontaneously hypertensive rats / 第二军医大学学报

Objective To investigate the protective effect of fenasinel dihydrochloride (FD) against stroke in stroke-prone spontaneously hypertensive rats (SHRSP). Methods Seven-week old male SHRSP were fed with NaCl 1g/d to induce stroke. Meanwhile, FD was injected intraperitcmeally at 1, 3, and 10 mg/(kg • d). The stroke onset time, Survival period after stroke, and neuronic deficit score after stroke were observed. Results FD delayed the onset of stroke n SHRSP and prolonged the Survival of the animals. Furthermore, low and medium doses FD also improved the Neuronal deficit score after stroke. Conclusion Our data suggest that FD has protective effect in SHRSP.

The effect of voluntary exercise and the influence of saline loading on systolic blood pressure and vascular lesions in stroke-prone SHR / 体力科学

The effects of voluntary exercise on resting systolic blood pressure and vascular lesions of stroke-prone spontaneously hypertensive rats (stroke-prone SHR) were investigated with and without 1 % saline loading. Forty male stroke-prone SHR aged 7 weeks were assigned to one of 4 experimental groups. Each consisted 10 animals ; sedentary control (S), sedentary with 1 % saline loading (SS), exercised control (E), and exercised with 1 % saline loading (ES) . Animals were sacrificed at the 5 th week. In the prehypertensive phase, resting caudal arterial systolic blood pressure was significantly lower in the E group than in the S group. However, after being loaded with 1 % saline, the ES group showed higher resting systolic blood pressure than those of the SS group. In addition, the ES group revealed severer renal, myocardial, and cerebrovascular lesions than those of the rest of the groups.