Intrarenal angiotensinogen: localization and regulation.
Multiple lines of evidence (physiologic, immunohistochemical, and molecular biologic) support the presence of a complete intrarenal renin-angiotensin system (RAS). Localization of angiotensinogen messenger ribonucleic acid (mRNA) within the proximal tubule, together with demonstration of renin and converting enzyme mRNAs within the kidney, provide the most persuasive evidence for local, independent synthesis. Data from a combination of in situ hybridization studies, Northern analysis, and physiologic manipulations lead us to propose that a major site for action of a local RAS is the proximal tubule. There, locally generated angiotensins may regulate sodium reabsorption and urine pH. A variety of factors appear to regulate renal angiotensinogen. For instance sodium depletion increases the expression of renal angiotensinogen (as well as renin mRNA), as does high potassium intake and androgen administration. In pathologic states, such as experimental heart failure, and certain models of hypertension, such as the spontaneously hypertensive rat, expression of renal angiotensinogen mRNA levels is altered. It is proposed that changes in the intrarenal RAS may play a role in the maintenance of homeostasis and in the pathophysiology of various disease states.
Ingelfinger, JR; Schunkert, H; Ellison, KE; Pivor, M; Zuo, WM; Pratt, R; Dzau, VJ
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