{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:46:50Z","timestamp":1793123210380,"version":"4.5.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,11,2]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">The gut\u2010derived hormone GLP\u20101 (glucagon\u2010like peptide\u20101) exerts beneficial effects against established risk factors for chronic kidney disease. GLP\u20101 influences renal function by stimulating diuresis and natriuresis and thus lowering arterial blood pressure. The role of the sympathetic nervous system has been implicated as an important link between obesity with elevated arterial pressure and chronic kidney disease. The primary aim of this study was to determine the contribution of renal sympathetic nerves on intrapelvic GLP\u20101\u2010mediated diuresis and natriuresis in high\u2010fat diet (HFD)\u2010induced obese rats.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Obesity was induced in rats by HFD for 12\u00a0weeks, followed by either surgical bilateral renal denervation or chronic subcutaneous endopeptidase neprilysin inhibition by sacubitril for a week. Diuretic and natriuretic responses to intrapelvic administration of the GLP\u20101R (GLP\u20101 receptor) agonist exendin\u20104 were monitored in anesthetized control and HFD rats. Renal GLP\u20101R expression and neprilysin expression and activity were measured. The effects of norepinephrine on the expression of GLP\u20101R and neprilysin in kidney epithelial LLC\u2010PK1 cells were also examined. We found that diuretic and natriuretic responses to exendin\u20104 were significantly reduced in the HFD obese rats compared with the control rats (cumulative urine flow at 40\u00a0minutes, 387\u00b132 versus 650\u00b165\u00a0\u00b5L\/gkw; cumulative sodium excretion at 40\u00a0minutes, 42\u00b15 versus 75\u00b110\u00a0\u00b5Eq\/gkw,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05). These responses in the HFD rats were restored after ablation of renal nerves (cumulative urine flow at 40\u00a0minutes, 625\u00b162 versus 387\u00b132\u00a0\u00b5L\/gkw; cumulative sodium excretion at 40\u00a0minutes, 70\u00b19 versus 42\u00b15\u00a0\u00b5Eq\/gkw,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05). Renal denervation induced significant reductions in arterial pressure and heart rate responses to intrapelvic GLP\u20101 in the HFD rats. Renal denervation also significantly increased the GLP\u20101R expression and reduced neprilysin expression and activity in renal tissues from the HFD rats. Chronic subcutaneous neprilysin inhibition by sacubitril increased GLP\u20101\u2013induced diuretic and natriuretic effects in the HFD rats. Finally, exposure of the renal epithelial cells to norepinephrine in vitro led to downregulation of GLP\u20101R expression but upregulation of neprilysin expression and activity.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">These results suggest that renal sympathetic nerve activation contributes to the blunted diuretic and natriuretic effects of GLP\u20101 in HFD obese rats. This study provides significant novel insight into the potential renal nerve\u2013neprilysin\u2013GLP\u20101 pathway involved in renal dysfunction during obesity that leads to hypertension.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.022542","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T09:05:24Z","timestamp":1635498324000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Role of Renal Sympathetic Nerves in GLP\u20101 (Glucagon\u2010Like Peptide\u20101) Receptor Agonist Exendin\u20104\u2010Mediated Diuresis and Natriuresis in Diet\u2010Induced Obese Rats"],"prefix":"10.1161","volume":"10","author":[{"given":"Xuefei","family":"Liu","sequence":"first","affiliation":[{"name":"Division of Basic Biomedical Sciences Sanford School of Medicine of the University of South Dakota Vermillion 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