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Journal of Undergraduate Research

Keywords

hypertension, RAS, renin-angiotensin system, angiotensin

College

Physical and Mathematical Sciences

Department

Chemistry and Biochemistry

Abstract

Hypertension (i.e., high blood pressure) is a significant health problem affecting more than 15% of the population contributing to the increased incidence of heart failure, kidney failure and stroke. The renin-angiotensin system (RAS) plays a pivotal role in salt and water homeostasis and the maintenance of vascular tone. This balance is achieved through the actions of the hormone, angiotensin II (Ang II), the biologically active component of the RAS, with its membrane-bound receptors. These receptors, designated as type 1 and type 2 (AT1R and AT2R), bind Ang II with equal affinity. The AT1R, however, which is localized in numerous tissues and cell types, is responsible for mediating most, if not all, of the well known physiological effects of Ang II. Our laboratory has shown that the human AT1R (hAT1R) gene contains at least four exons and is encoded by four distinct alternatively spliced mRNA transcripts (1) (Figure 1). Sequence analysis suggested that the hAT1R-A and -C transcripts may encode a novel hAT1R that has a 32 amino acid extension at the amino terminus given that exon 3 harbors an ATG translation initiation start site that is in frame with the known ATG start site located in exon 4. Therefore, the specific aim of this proposal was to investigate whether hAT1R mRNA transcripts $A# and $C# generate a novel hAT1R and to determine whether these receptors are functionally distinct.

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