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10.1161/CIRCRESAHA.119.315338 http://scihub22266oqcxt.onion/10.1161/CIRCRESAHA.119.315338 31545149!6842127!31545149     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Circ+Res 2019 ; 125 (11): 989-1002 Nephropedia Template TP {{tp|p=31545149|t=2019. Leptin Induces Hypertension Acting on Transient Receptor Potential Melastatin 7 Channel in the Carotid Body |pdf=|usr=}}{{31545149}} gab.com Text Leptin Induces Hypertension Acting on Transient Receptor Potential Melastatin 7 Channel in the Carotid Body JO: Circ Res http://www.kidney.de/pget.php?&tw=1&pmid=31545149 #FOAvip RATIONALE: Obesity leads to resistant hypertension and mechanisms are poorly understood, but high plasma levels of leptin have been implicated. Leptin increases blood pressure acting both centrally in the dorsomedial hypothalamus and peripherally. Sites of the peripheral hypertensive effect of leptin have not been identified. We previously reported that leptin enhanced activity of the carotid sinus nerve, which transmits chemosensory input from the carotid bodies (CBs) to the medullary centers, and this effect was abolished by nonselective blockers of Trp (transient receptor potential) channels. We searched our mouse CB transcriptome database and found that the Trpm7 (transient receptor potential melastatin 7) channel was the most abundant Trp channel. OBJECTIVE: To examine if leptin induces hypertension acting on the CB Trpm7. METHODS AND RESULTS: C57BL/6J (n=79), leptin receptor (LepR(b)) deficient db/db mice (n=22), and LepRb-EGFP (n=4) mice were used. CB Trpm7 and LepR(b) gene expression was determined and immunohistochemistry was performed; CB glomus cells were isolated and Trpm7-like current was recorded. Blood pressure was recorded continuously in (1) leptin-treated C57BL/6J mice with intact and denervated CB; (2) leptin-treated C57BL/6J mice, which also received a nonselective Trpm7 blocker FTY720 administered systemically or topically to the CB area; (3) leptin-treated C57BL/6J mice transfected with Trpm7 small hairpin RNA to the CB, and (4) Lepr(b) deficient obese db/db mice before and after Lepr(b) expression in CB. Leptin receptor and Trpm7 colocalized in the CB glomus cells. Leptin induced a nonselective cation current in these cells, which was inhibited by Trpm7 blockers. Leptin induced hypertension in C57BL/6J mice, which was abolished by CB denervation, Trpm 7 blockers, and Trpm7 small hairpin RNA applied to CBs. Lepr(b) overexpression in CB of Lepr(b)-deficient db/db mice demethylated the Trpm7 promoter, increased Trpm7 gene expression, and induced hypertension. CONCLUSIONS: We conclude that leptin induces hypertension acting on Trmp7 in CB, which opens horizons for new therapy. Twit Text FOAVip Leptin Induces Hypertension Acting on Transient Receptor Potential Melastatin 7 Channel in the Carotid Body ????Circ Res http://www.kidney.de/pget.php?&tw=1&pmid=31545149 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=31545149 #FOAvip English Wikipedia <ref>{{Cite pmid|31545149}}</ref> Leptin Induces Hypertension Acting on Transient Receptor Potential Melastatin 7 Channel in the Carotid Body #MMPMID31545149 Shin MK; Eraso CC; Mu YP; Gu C; Yeung BHY; Kim LJ; Liu XR; Wu ZJ; Paudel O; Pichard LE; Shirahata M; Tang WY; Sham JSK; Polotsky VY Circ Res 2019[Nov]; 125 (11): 989-1002 PMID31545149show ga RATIONALE: Obesity leads to resistant hypertension and mechanisms are poorly understood, but high plasma levels of leptin have been implicated. Leptin increases blood pressure acting both centrally in the dorsomedial hypothalamus and peripherally. Sites of the peripheral hypertensive effect of leptin have not been identified. We previously reported that leptin enhanced activity of the carotid sinus nerve, which transmits chemosensory input from the carotid bodies (CBs) to the medullary centers, and this effect was abolished by nonselective blockers of Trp (transient receptor potential) channels. We searched our mouse CB transcriptome database and found that the Trpm7 (transient receptor potential melastatin 7) channel was the most abundant Trp channel. OBJECTIVE: To examine if leptin induces hypertension acting on the CB Trpm7. METHODS AND RESULTS: C57BL/6J (n=79), leptin receptor (LepR(b)) deficient db/db mice (n=22), and LepRb-EGFP (n=4) mice were used. CB Trpm7 and LepR(b) gene expression was determined and immunohistochemistry was performed; CB glomus cells were isolated and Trpm7-like current was recorded. Blood pressure was recorded continuously in (1) leptin-treated C57BL/6J mice with intact and denervated CB; (2) leptin-treated C57BL/6J mice, which also received a nonselective Trpm7 blocker FTY720 administered systemically or topically to the CB area; (3) leptin-treated C57BL/6J mice transfected with Trpm7 small hairpin RNA to the CB, and (4) Lepr(b) deficient obese db/db mice before and after Lepr(b) expression in CB. Leptin receptor and Trpm7 colocalized in the CB glomus cells. Leptin induced a nonselective cation current in these cells, which was inhibited by Trpm7 blockers. Leptin induced hypertension in C57BL/6J mice, which was abolished by CB denervation, Trpm 7 blockers, and Trpm7 small hairpin RNA applied to CBs. Lepr(b) overexpression in CB of Lepr(b)-deficient db/db mice demethylated the Trpm7 promoter, increased Trpm7 gene expression, and induced hypertension. CONCLUSIONS: We conclude that leptin induces hypertension acting on Trmp7 in CB, which opens horizons for new therapy. |*Blood Pressure/drug effects[MESH] |*Leptin[MESH] |Animals[MESH] |Antihypertensive Agents/pharmacology[MESH] |Carotid Body/drug effects/*metabolism/physiopathology[MESH] |Denervation[MESH] |Disease Models, Animal[MESH] |Hypertension/*chemically induced/metabolism/physiopathology/prevention & control[MESH] |Male[MESH] |Mice, Inbred C57BL[MESH] |Mice, Knockout[MESH] |Obesity/complications[MESH] |Receptors, Leptin/deficiency/genetics/*metabolism[MESH] |Signal Transduction[MESH]Leptin Induces Hypertension Acting on Transient Receptor Potential Mel(epmc).pdf DeepDyve Pubget Overpricing