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Previously we have shown that GLP-1 activates afferent renal nerve to increase efferent renal sympathetic nerve activity that negates the diuresis and natriuresis as a negative feedback mechanism in normal rats. However, renal effects of GLP-1 in heart failure (HF) has not been elucidated. The present study was designed to assess GLP-1-induced diuresis and natriuresis in rats with HF and its interactions with renal nerve activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HF was induced in rats by coronary artery ligation. The direct recording of afferent renal nerve activity (ARNA) with intrapelvic injection of GLP-1 and total renal sympathetic nerve activity (RSNA) with intravenous infusion of GLP-1 were performed. GLP-1 receptor expression in renal pelvis, densely innervated by afferent renal nerve, was assessed by real-time PCR and western blot analysis. In separate group of rats after coronary artery ligation selective afferent renal denervation (A-RDN) was performed by periaxonal application of capsaicin, then intravenous infusion of GLP-1-induced diuresis and natriuresis were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In HF, compared to sham-operated control; (1) response of increase in ARNA to intrapelvic injection of GLP-1 was enhanced (3.7\u2009\u00b1\u20090.4 vs. 2.0\u2009\u00b1\u20090.4\u00a0\u00b5V\u00a0s), (2) GLP-1 receptor expression was increased in renal pelvis, (3) response of increase in RSNA to intravenous infusion of GLP-1 was enhanced (132\u2009\u00b1\u200930% vs. 70\u2009\u00b1\u200916% of the baseline level), and (4) diuretic and natriuretic responses to intravenous infusion of GLP-1 were blunted (urine flow 53.4\u2009\u00b1\u20094.3 vs. 78.6\u2009\u00b1\u20094.4\u00a0\u00b5l\/min\/gkw, sodium excretion 7.4\u2009\u00b1\u20090.8 vs. 10.9\u2009\u00b1\u20091.0 \u00b5Eq\/min\/gkw). A-RDN induced significant increases in diuretic and natriuretic responses to GLP-1 in HF (urine flow 96.0\u2009\u00b1\u20091.9 vs. 53.4\u2009\u00b1\u20094.3\u00a0\u00b5l\/min\/gkw, sodium excretion 13.6\u2009\u00b1\u20091.4 vs. 7.4\u2009\u00b1\u20090.8 \u00b5Eq\/min\/gkw).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The excessive activation of neural circuitry involving afferent and efferent renal nerves suppresses diuretic and natriuretic responses to GLP-1 in HF. These pathophysiological responses to GLP-1 might be involved in the interaction between incretin-based medicines and established HF condition. RDN restores diuretic and natriuretic effects of GLP-1 and thus has potential beneficial therapeutic implication for diabetic HF patients.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12933-020-01029-0","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T11:02:59Z","timestamp":1588935779000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["GLP-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervation"],"prefix":"10.1186","volume":"19","author":[{"given":"Kenichi","family":"Katsurada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam S.","family":"Nandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeru M.","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaushik P.","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,8]]},"reference":[{"issue":"4","key":"1029_CR1","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1152\/physrev.00034.2006","volume":"87","author":"JJ Holst","year":"2007","unstructured":"Holst JJ. 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