Hyperglycaemia-induced intrarenal RAS activation: the contribution of metabolic pathways
Hyperglycaemia-induced activation of the renin-angiotensin system (RAS) has been observed in normal and diabetic humans. Our main objective was to determine whether the mechanism involved a physical or metabolic effect of glucose. First, Sprague-Dawley rats of the CD strain were given sequential int...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publications
2002-03-01
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| Series: | Journal of the Renin-Angiotensin-Aldosterone System |
| Online Access: | https://doi.org/10.3317/jraas.2002.003 |
| _version_ | 1797288725254766592 |
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| author | M Cecilia Lansang Suzette Y Osei Caroline Coletti Janelle Krupinski Norman K Hollenberg |
| author_facet | M Cecilia Lansang Suzette Y Osei Caroline Coletti Janelle Krupinski Norman K Hollenberg |
| author_sort | M Cecilia Lansang |
| collection | DOAJ |
| description | Hyperglycaemia-induced activation of the renin-angiotensin system (RAS) has been observed in normal and diabetic humans. Our main objective was to determine whether the mechanism involved a physical or metabolic effect of glucose. First, Sprague-Dawley rats of the CD strain were given sequential intravenous (i.v.) doses of 0.01, 0.1, 1.0, and 3.0 mg/kg candesartan 30 minutes apart, in the presence of a continuous i.v. infusion of dextrose 20% in water (D20W). The 0.1 mg/kg dose produced a maximal renal blood flow (RBF) response and was used thereafter. Another set of animals then received an infusion of either normal saline (NS), dextrose 5% in water (D5W) or dextrose 20% in water (D20W) for 2 hours, followed by candesartan 0.1 mg/kg i.v. Finally, the response to candesartan 0.1 mg/kg i.v. during D20W infusion was compared with that during infusion of 2-deoxyglucose (2DG), a glucose analogue that competitively inhibits the glycolytic enzyme, hexokinase. RBF (electromagnetic flowmeter), blood pressure (BP), blood glucose, and urine glucose were monitored. There was no significant RBF response to candesartan on either NS (6.01±0.48 to 6.20±0.49 ml/minute/g kidney; p=0.216) or D5W (7.63±1.20 to 7.58±1.39 ml/minute/g kidney; p=0.965), whereas there was a significant response to D20W (6.64±0.59 to 7.46±0.67 ml/minute/g kidney; p=0.002). The RBF response was significantly enhanced by D20W compared with 2DG (change in RBF: 0.82±0.22 vs . -0.04±0.26; p=0.05), despite similar BP, blood glucose, and urine glucose. Glucose acts, at least in part, through intracellular utilisation to induce RAS activation, as manifested by an enhanced renal vascular response to an angiotensin II antagonist. |
| first_indexed | 2024-03-07T18:53:40Z |
| format | Article |
| id | doaj.art-c61ced86037d4fc9bd2db72481050192 |
| institution | Directory Open Access Journal |
| issn | 1470-3203 |
| language | English |
| last_indexed | 2024-03-07T18:53:40Z |
| publishDate | 2002-03-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Journal of the Renin-Angiotensin-Aldosterone System |
| spelling | doaj.art-c61ced86037d4fc9bd2db724810501922024-03-02T00:52:35ZengSAGE PublicationsJournal of the Renin-Angiotensin-Aldosterone System1470-32032002-03-01310.3317/jraas.2002.003Hyperglycaemia-induced intrarenal RAS activation: the contribution of metabolic pathwaysM Cecilia LansangSuzette Y OseiCaroline ColettiJanelle KrupinskiNorman K HollenbergHyperglycaemia-induced activation of the renin-angiotensin system (RAS) has been observed in normal and diabetic humans. Our main objective was to determine whether the mechanism involved a physical or metabolic effect of glucose. First, Sprague-Dawley rats of the CD strain were given sequential intravenous (i.v.) doses of 0.01, 0.1, 1.0, and 3.0 mg/kg candesartan 30 minutes apart, in the presence of a continuous i.v. infusion of dextrose 20% in water (D20W). The 0.1 mg/kg dose produced a maximal renal blood flow (RBF) response and was used thereafter. Another set of animals then received an infusion of either normal saline (NS), dextrose 5% in water (D5W) or dextrose 20% in water (D20W) for 2 hours, followed by candesartan 0.1 mg/kg i.v. Finally, the response to candesartan 0.1 mg/kg i.v. during D20W infusion was compared with that during infusion of 2-deoxyglucose (2DG), a glucose analogue that competitively inhibits the glycolytic enzyme, hexokinase. RBF (electromagnetic flowmeter), blood pressure (BP), blood glucose, and urine glucose were monitored. There was no significant RBF response to candesartan on either NS (6.01±0.48 to 6.20±0.49 ml/minute/g kidney; p=0.216) or D5W (7.63±1.20 to 7.58±1.39 ml/minute/g kidney; p=0.965), whereas there was a significant response to D20W (6.64±0.59 to 7.46±0.67 ml/minute/g kidney; p=0.002). The RBF response was significantly enhanced by D20W compared with 2DG (change in RBF: 0.82±0.22 vs . -0.04±0.26; p=0.05), despite similar BP, blood glucose, and urine glucose. Glucose acts, at least in part, through intracellular utilisation to induce RAS activation, as manifested by an enhanced renal vascular response to an angiotensin II antagonist.https://doi.org/10.3317/jraas.2002.003 |
| spellingShingle | M Cecilia Lansang Suzette Y Osei Caroline Coletti Janelle Krupinski Norman K Hollenberg Hyperglycaemia-induced intrarenal RAS activation: the contribution of metabolic pathways Journal of the Renin-Angiotensin-Aldosterone System |
| title | Hyperglycaemia-induced intrarenal RAS activation: the contribution of metabolic pathways |
| title_full | Hyperglycaemia-induced intrarenal RAS activation: the contribution of metabolic pathways |
| title_fullStr | Hyperglycaemia-induced intrarenal RAS activation: the contribution of metabolic pathways |
| title_full_unstemmed | Hyperglycaemia-induced intrarenal RAS activation: the contribution of metabolic pathways |
| title_short | Hyperglycaemia-induced intrarenal RAS activation: the contribution of metabolic pathways |
| title_sort | hyperglycaemia induced intrarenal ras activation the contribution of metabolic pathways |
| url | https://doi.org/10.3317/jraas.2002.003 |
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