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Sex Differences in Renal Responses to Hyperglycemia, l-Arginine, and l-NMMA in Humans With Uncomplicated Type 1 Diabetes

OBJECTIVE: Women exhibit exaggerated renal hemodynamic responses to hyperglycemia, which may promote kidney disease progression. Our aim was to determine if increased nitric oxide generation by l-arginine infusion would reverse this deleterious response to clamped hyperglycemia in women with type 1...

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Autores principales: Cherney, David Z.I., Scholey, James W., Sochett, Etienne B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631825/
https://www.ncbi.nlm.nih.gov/pubmed/23250800
http://dx.doi.org/10.2337/dc12-1305
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author Cherney, David Z.I.
Scholey, James W.
Sochett, Etienne B.
author_facet Cherney, David Z.I.
Scholey, James W.
Sochett, Etienne B.
author_sort Cherney, David Z.I.
collection PubMed
description OBJECTIVE: Women exhibit exaggerated renal hemodynamic responses to hyperglycemia, which may promote kidney disease progression. Our aim was to determine if increased nitric oxide generation by l-arginine infusion would reverse this deleterious response to clamped hyperglycemia in women with type 1 diabetes mellitus. RESEARCH DESIGN AND METHODS: Renal function, blood pressure, and plasma cyclic guanosine monophosphate (cGMP) were measured in 20 men and 15 women with type 1 diabetes mellitus during clamped euglycemia and clamped hyperglycemia. Renal function, blood pressure, and plasma cGMP responses to graded infusions of intravenous l-arginine and N(G)-monomethyl-l-arginine (l-NMMA) were measured during clamped hyperglycemia. RESULTS: Subjects were young, normotensive, normoalbuminuric men and women who adhered to a high-sodium, moderate-protein diet. Plasma cGMP levels during euglycemia were generally lower in men compared with women, and systolic blood pressure (SBP) was higher in men. In response to hyperglycemia, cGMP levels did not change in men but did decline in women (Δ−1.10 ± 0.20 vs. Δ+0.05 ± 0.20 pmol/L, between-group effect of hyperglycemia on cGMP; P = 0.012). Hyperglycemia also was associated with an increase in SBP, glomerular filtration rate (GFR) (124 ± 6 to 143 ± 7 mL/min/1.73 m(2); P = 0.003) and filtration fraction (FF) in women, but these parameters did not change in men. In response to l-arginine during hyperglycemia, the increase in cGMP was exaggerated in women versus men and GFR and FF decreased in women only, back toward baseline values observed during clamped euglycemia. l-NMMA infusion did not exaggerate changes in hemodynamic function in response to hyperglycemia. CONCLUSIONS:  l-Arginine reversed the renal hemodynamic effects of hyperglycemia in women, suggesting that nitric oxide is an important regulator of sex-dependent vascular responses to hyperglycemia in humans.
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spelling pubmed-36318252014-05-01 Sex Differences in Renal Responses to Hyperglycemia, l-Arginine, and l-NMMA in Humans With Uncomplicated Type 1 Diabetes Cherney, David Z.I. Scholey, James W. Sochett, Etienne B. Diabetes Care Original Research OBJECTIVE: Women exhibit exaggerated renal hemodynamic responses to hyperglycemia, which may promote kidney disease progression. Our aim was to determine if increased nitric oxide generation by l-arginine infusion would reverse this deleterious response to clamped hyperglycemia in women with type 1 diabetes mellitus. RESEARCH DESIGN AND METHODS: Renal function, blood pressure, and plasma cyclic guanosine monophosphate (cGMP) were measured in 20 men and 15 women with type 1 diabetes mellitus during clamped euglycemia and clamped hyperglycemia. Renal function, blood pressure, and plasma cGMP responses to graded infusions of intravenous l-arginine and N(G)-monomethyl-l-arginine (l-NMMA) were measured during clamped hyperglycemia. RESULTS: Subjects were young, normotensive, normoalbuminuric men and women who adhered to a high-sodium, moderate-protein diet. Plasma cGMP levels during euglycemia were generally lower in men compared with women, and systolic blood pressure (SBP) was higher in men. In response to hyperglycemia, cGMP levels did not change in men but did decline in women (Δ−1.10 ± 0.20 vs. Δ+0.05 ± 0.20 pmol/L, between-group effect of hyperglycemia on cGMP; P = 0.012). Hyperglycemia also was associated with an increase in SBP, glomerular filtration rate (GFR) (124 ± 6 to 143 ± 7 mL/min/1.73 m(2); P = 0.003) and filtration fraction (FF) in women, but these parameters did not change in men. In response to l-arginine during hyperglycemia, the increase in cGMP was exaggerated in women versus men and GFR and FF decreased in women only, back toward baseline values observed during clamped euglycemia. l-NMMA infusion did not exaggerate changes in hemodynamic function in response to hyperglycemia. CONCLUSIONS:  l-Arginine reversed the renal hemodynamic effects of hyperglycemia in women, suggesting that nitric oxide is an important regulator of sex-dependent vascular responses to hyperglycemia in humans. American Diabetes Association 2013-05 2013-04-13 /pmc/articles/PMC3631825/ /pubmed/23250800 http://dx.doi.org/10.2337/dc12-1305 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Research
Cherney, David Z.I.
Scholey, James W.
Sochett, Etienne B.
Sex Differences in Renal Responses to Hyperglycemia, l-Arginine, and l-NMMA in Humans With Uncomplicated Type 1 Diabetes
title Sex Differences in Renal Responses to Hyperglycemia, l-Arginine, and l-NMMA in Humans With Uncomplicated Type 1 Diabetes
title_full Sex Differences in Renal Responses to Hyperglycemia, l-Arginine, and l-NMMA in Humans With Uncomplicated Type 1 Diabetes
title_fullStr Sex Differences in Renal Responses to Hyperglycemia, l-Arginine, and l-NMMA in Humans With Uncomplicated Type 1 Diabetes
title_full_unstemmed Sex Differences in Renal Responses to Hyperglycemia, l-Arginine, and l-NMMA in Humans With Uncomplicated Type 1 Diabetes
title_short Sex Differences in Renal Responses to Hyperglycemia, l-Arginine, and l-NMMA in Humans With Uncomplicated Type 1 Diabetes
title_sort sex differences in renal responses to hyperglycemia, l-arginine, and l-nmma in humans with uncomplicated type 1 diabetes
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631825/
https://www.ncbi.nlm.nih.gov/pubmed/23250800
http://dx.doi.org/10.2337/dc12-1305
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