Document Detail


Intrarenal ghrelin infusion stimulates distal nephron-dependent sodium reabsorption in normal rats.
MedLine Citation:
PMID:  21220707     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ghrelin is a 28-amino acid peptide hormone that exerts powerful orexigenic effects. Ghrelin receptor expression has been reported in the kidney, but the role of ghrelin in the kidney is unknown. The present studies confirmed ghrelin receptor mRNA expression in the kidneys of normal Sprague Dawley rats (n=6) using reverse transcription polymerase chain reaction (PCR) and sequencing of the 588-bp PCR product. To test intrarenal ghrelin action, uninephrectomized rats received 3 cumulative 1-hour renal interstitial (RI) infusions of 5% dextrose in water (vehicle, n=21), ghrelin (n=10), ghrelin plus specific ghrelin receptor antagonist [D-Lys-3]-GHRP-6 (n=24), or [D-Lys-3]-GHRP-6 alone (n=32). Mean arterial pressure (MAP), urine sodium excretion rate (U(Na)V), glomerular filtration rate (GFR), fractional excretion of sodium (FE(Na)), and fractional excretion of lithium (FE(Li)) were calculated for each period. RI ghrelin infusion significantly decreased U(Na)V to 86 ± 4.9% (P<0.05), 74 ± 6.5% (P<0.01), and 62 ± 10% (P<0.01) of baseline during periods 1 to 3, respectively. Ghrelin also significantly decreased FE(Na) to 68 ± 11% (P<0.05), 57 ± 8.6% (P<0.001), and 59 ± 12% (P<0.01) of baseline, without changing GFR or FE(Li). Identical ghrelin infusions in the presence of [D-Lys-3]-GHRP-6 failed to permit reductions in U(Na)V or FE(Na). Following [D-Lys-3]-GHRP-6 infusion alone, U(Na)V increased from 0.06 ± 0.01 to 0.18 ± 0.03 μmol/min (P<0.0001). Concomitant increases in FE(Na) were also observed (0.23 ± 0.03% to 0.51 ± 0.06% [P<0.001]), without changes in MAP, GFR, or FE(Li). Together, these data introduce a novel intrarenal ghrelin-ghrelin receptor system, which, on activation, significantly increases Na(+) reabsorption at the level of the distal nephron.
Authors:
Brandon A Kemp; Nancy L Howell; Jasmine T Gray; Susanna R Keller; Ralf M Nass; Shetal H Padia
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-01-10
Journal Detail:
Title:  Hypertension     Volume:  57     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-17     Completed Date:  2011-04-14     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  633-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Blood Pressure / drug effects*,  physiology
Female
Ghrelin / metabolism,  pharmacology*
Glomerular Filtration Rate / drug effects,  physiology
Kidney / drug effects*,  metabolism
Natriuresis / drug effects,  physiology
Nephrons / drug effects*,  metabolism
Oligopeptides / pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Ghrelin / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Sodium / metabolism*
Grant Support
ID/Acronym/Agency:
5K08HL093353/HL/NHLBI NIH HHS; K08 HL093353/HL/NHLBI NIH HHS; K08 HL093353-02/HL/NHLBI NIH HHS; K08 HL093353-03/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/GHRP-6, Lys(3)-; 0/Ghrelin; 0/Oligopeptides; 0/Receptors, Ghrelin; 9NEZ333N27/Sodium
Comments/Corrections

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