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M. C. Lansang, S. Y. Osei, C. Coletti, J. Krupinski, N. K. Hollenberg, P-352: The mechanism of hyperglycemia-induced RAS activation: Contribution of metabolic pathways, American Journal of Hypertension, Volume 14, Issue S1, April 2001, Page 148A, https://doi.org/10.1038/ajh.2001.1
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Abstract
Hyperglycemia-induced RAS activation has been observed in normal and diabetic humans. The main objective was to determine whether this phenomenon reflected the physical or metabolic effects of glucose loading. First, an animal model was developed. Using CD rats, the relationship between candesartan dose and renal vascular response during hyperglycemia was examined by giving sequential, increasing doses of candesartan (0.01-3.0 mg/kg i.v.) 30 min apart in the presence of a continuous dextrose 20% in water (D20W) infusion. The 0.1 mg/kg dose produced a maximal renal blood flow (RBF) response and was used thereafter. Another set of animals was then infused with normal saline (NS), dextrose 5% in water (D5W) or D20W for 2 hrs followed by candesartan 0.1 mg/kg i.v. Finally, the responses to candesartan during infusion of D20W and of 2-deoxyglucose (2DG)–an analog of glucose that acts as a competitive inhibitor of the glycolytic enzyme hexokinase– were compared. RBF, BP, blood glucose and urine glucose were monitored.
There was no significant RBF response to candesartan in either the NS group (6.0 ± 0.5 mL/min/g kidney to 6.2 ± 0.5; p=0.216) or the D5W group (7.6 ± 1.2 to 7.6 ± 1.4; p=0.965), whereas there was a significant response in the D20W group (6.6 ± 0.6 to 7.5 ± 0.7; p=0.002). The RBF response was significantly enhanced by D20W compared to 2DG (delta RBF: 0.82 ± 0.22 vs -0.04 ± 0.26; p=0.050). BP, blood glucose and urine glucose were similar in the 2 groups. Glucose acts, at least in part, through intracellular utilization to induce RAS activation, as manifested by an enhanced renal vascular response to an AngII antagonist.
