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      1. Author :
        Zhang, J.; Preda, D. V.; Vasquez, K. O.; Morin, J.; Delaney, J.; Bao, B.; Percival, M. D.; Xu, D.; McKay, D.; Klimas, M.; Bednar, B.; Sur, C.; Gao, D. Z.; Madden, K.; Yared, W.; Rajopadhye, M.; Peterson, J. D.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Am J Physiol Renal Physiol
      6. Products :
      7. Volume :
        303
      8. Issue :
        N/A
      9. Page Numbers :
        F593-603
      10. Research Area :
        N/A
      11. Keywords :
        ReninSense 680 FAST, FMT, Animal Feed/analysis; Animals; Cathepsin D; Cathepsin G; Female; Fluorescent Dyes/*pharmacology; Humans; Mice; Mice, Inbred C57BL; Peptides/*pharmacology; Peptidyl-Dipeptidase A/metabolism; Rats; Renin/*blood/*metabolism; Renin-Angiotensin System/physiology; Sensitivity and Specificity; Sodium, Dietary
      12. Abstract :
        The renin-angiotensin system (RAS) is well studied for its regulation of blood pressure and fluid homeostasis, as well as for increased activity associated with a variety of diseases and conditions, including cardiovascular disease, diabetes, and kidney disease. The enzyme renin cleaves angiotensinogen to form angiotensin I (ANG I), which is further cleaved by angiotensin-converting enzyme to produce ANG II. Although ANG II is the main effector molecule of the RAS, renin is the rate-limiting enzyme, thus playing a pivotal role in regulating RAS activity in hypertension and organ injury processes. Our objective was to develop a near-infrared fluorescent (NIRF) renin-imaging agent for noninvasive in vivo detection of renin activity as a measure of tissue RAS and in vitro plasma renin activity. We synthesized a renin-activatable agent, ReninSense 680 FAST (ReninSense), using a NIRF-quenched substrate derived from angiotensinogen that is cleaved specifically by purified mouse and rat renin enzymes to generate a fluorescent signal. This agent was assessed in vitro, in vivo, and ex vivo to detect and quantify increases in plasma and kidney renin activity in sodium-sensitive inbred C57BL/6 mice maintained on a low dietary sodium and diuretic regimen. Noninvasive in vivo fluorescence molecular tomographic imaging of the ReninSense signal in the kidney detected increased renin activity in the kidneys of hyperreninemic C57BL/6 mice. The agent also effectively detected renin activity in ex vivo kidneys, kidney tissue sections, and plasma samples. This approach could provide a new tool for assessing disorders linked to altered tissue and plasma renin activity and to monitor the efficacy of therapeutic treatments.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22674025
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10572
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