This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The spontaneously hypertensive rat (SHR) is the most widely studied animal model of genetic hypertension. Mean arterial blood pressure (MABP) progressively increases in the SHR between 6-12 weeks of age, after which pressure reaches a hypertensive plateau. Dr. Kost's lab has shown that the increase in MABP can be be prevented by treatment with an angiotensin converting enzyme inhibitor (ACE-I) during this developmental phase. Interestingly, when ACE-I treatment is later withdrawn, MABP increases to a plateau that remains 20-30 mmHg below control SHR values. This reduction in MABP persists throughout the lifetime of the SHR, thus early transient treatment permanently alters the hypertensive PHENOTYPE of the rat. It is likely that the permanent PHENOTYPIC changes we have observed (altered blood pressure) corresponds with permanent GENOTYPIC changes (altered gene expression). The current proposal is designed to test the hypothesis that the sustained reduction in MABP following early transient inhibition of the renin-angiotensin-system (RAS)in SHR involves a permanent alteration of gene expression in specific brain and kidney regions that are known to be involved in blood pressure regulation. Both pharmacological and biochemical approaches will be utilized to assess these postulated GENOTYPIC alterations.
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