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10.1080/0886022X.2021.1879856 http://scihub22266oqcxt.onion/10.1080/0886022X.2021.1879856 33541194!8901277!33541194     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=33541194&cmd=llinks): Failed to open stream: HTTP request failed! 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Inhibition of neprilysin with sacubitril without RAS blockage aggravates renal disease in Dahl SS rats |pdf=|usr=}}{{33541194}} gab.com Text Inhibition of neprilysin with sacubitril without RAS blockage aggravates renal disease in Dahl SS rats JO: Ren Fail http://www.kidney.de/pget.php?&tw=1&pmid=33541194 #FOAvip Salt-sensitive (SS) hypertension is accompanied with severe cardiorenal complications. In this condition, elevated blood pressure (BP) resulting from salt retention is associated with counterintuitively lower levels of atrial natriuretic peptide (ANP). In plasma, ANP is degraded by the neprilysin; therefore, pharmacological inhibition of this metalloprotease (i.e., with sacubitril) can be employed to increase ANP level. We have shown earlier that sacubitril in combination with valsartan (75 mug/day each) had beneficial effects on renal function in Dahl SS rats. The goal of this study was to evaluate the effects of a higher dose of sacubitril on renal damage in this model. To induce hypertension, male Dahl SS rats were fed a 4% NaCl diet (HS) for 21 days, and were administered sacubitril (125 mug/day) or vehicle via s.c. osmotic pumps. At the end of the HS challenge, both groups exhibited similar outcomes for GFR, heart weight, plasma electrolytes, BUN, and creatinine. Sacubitril exacerbated kidney hypertrophy, but did not affect levels of renal fibrosis. We also observed aggravated glomerular lesions and increased formation of protein casts in the sacubitril-treated animals compared to controls. Thus, in Dahl SS rats, administration of sacubitril without renin-angiotensin-system blockage had adverse effects on renal disease progression, particularly in regards to glomerular damage and protein cast formation. We can speculate that while ANP levels are increased because of neprilysin inhibition, there are off-target effects of sacubitril, which are detrimental to renal function in the SS hypertensive state. Twit Text FOAVip Inhibition of neprilysin with sacubitril without RAS blockage aggravates renal disease in Dahl SS rats ????Ren Fail http://www.kidney.de/pget.php?&tw=1&pmid=33541194 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33541194 #FOAvip English Wikipedia <ref>{{Cite pmid|33541194}}</ref> Inhibition of neprilysin with sacubitril without RAS blockage aggravates renal disease in Dahl SS rats #MMPMID33541194 Polina I; Spicer MJ; Domondon M; Schibalski RS; Sarsenova E; Sultanova RF; Ilatovskaya DV Ren Fail 2021[Dec]; 43 (1): 315-324 PMID33541194show ga Salt-sensitive (SS) hypertension is accompanied with severe cardiorenal complications. In this condition, elevated blood pressure (BP) resulting from salt retention is associated with counterintuitively lower levels of atrial natriuretic peptide (ANP). In plasma, ANP is degraded by the neprilysin; therefore, pharmacological inhibition of this metalloprotease (i.e., with sacubitril) can be employed to increase ANP level. We have shown earlier that sacubitril in combination with valsartan (75 mug/day each) had beneficial effects on renal function in Dahl SS rats. The goal of this study was to evaluate the effects of a higher dose of sacubitril on renal damage in this model. To induce hypertension, male Dahl SS rats were fed a 4% NaCl diet (HS) for 21 days, and were administered sacubitril (125 mug/day) or vehicle via s.c. osmotic pumps. At the end of the HS challenge, both groups exhibited similar outcomes for GFR, heart weight, plasma electrolytes, BUN, and creatinine. Sacubitril exacerbated kidney hypertrophy, but did not affect levels of renal fibrosis. We also observed aggravated glomerular lesions and increased formation of protein casts in the sacubitril-treated animals compared to controls. Thus, in Dahl SS rats, administration of sacubitril without renin-angiotensin-system blockage had adverse effects on renal disease progression, particularly in regards to glomerular damage and protein cast formation. We can speculate that while ANP levels are increased because of neprilysin inhibition, there are off-target effects of sacubitril, which are detrimental to renal function in the SS hypertensive state. |Aminobutyrates/administration & dosage/*adverse effects[MESH] |Animals[MESH] |Atrial Natriuretic Factor/blood/metabolism[MESH] |Biphenyl Compounds/administration & dosage/*adverse effects[MESH] |Disease Models, Animal[MESH] |Dose-Response Relationship, Drug[MESH] |Humans[MESH] |Hypertension/blood/complications/*drug therapy[MESH] |Kidney Glomerulus/*drug effects/pathology[MESH] |Male[MESH] |Neprilysin/*antagonists & inhibitors/metabolism[MESH] |Rats[MESH] |Rats, Inbred Dahl[MESH]Inhibition of neprilysin with sacubitril without RAS blockage aggravat(epmc).pdf DeepDyve Pubget Overpricing