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Effect of acute hyperglycaemia on sodium handling and excretion of nitric oxide metabolites, bradykinin, and cGMP in Type 1 diabetes mellitus
Author(s) -
Šimková R.,
Kazdová L.,
Karasová L.,
Simek S.,
Pelikánová T.
Publication year - 2004
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.2004.01270.x
Subject(s) - medicine , nitric oxide , type 2 diabetes mellitus , diabetes mellitus , bradykinin , endocrinology , excretion , sodium , pharmacology , chemistry , receptor , organic chemistry
Aims The aim of this study was to evaluate the effect of acutely induced hyperglycaemia on renal sodium handling and to explore the role of the bradykinin‐nitric oxide‐cGMP signalling pathway. Patients and methods We compared 20 Type 1 diabetic (DM1) patients without microalbuminuria with 15 weight‐, age‐, and sex‐matched healthy controls (C). Clearances of para‐aminohippuric acid (C PAH ), inulin (C in ), lithium, sodium, and urinary nitrite/nitrate (NO x ), cGMP and bradykinin excretion rates were measured in two 90‐min periods: a glycaemic clamp‐induced euglycaemia (5 mmol/l—period I) and hyperglycaemia (12 mmol/l—period II) (Study 1) and during time‐controlled euglycaemia (5 mmol/l—period I and 5 mmol/l—period II) to avoid the effects of time and volume load (Study 2). Results C in and C PAH were not significantly different during euglycaemia (period I of Study 1) in DM1 and controls, whereas fractional excretion of sodium was decreased in DM1 (1.84 ± 0.75 vs. 2.36 ± 0.67%; P < 0.05) due to an increase in fractional distal tubular reabsorption of sodium (94.01 ± 1.94 vs. 92.24 ± 2.47%; P < 0.05). A comparison of changes during Study 1 and Study 2 revealed acute hyperglycaemia did not change renal haemodynamics significantly, while fractional distal tubular reabsorption of sodium increased (DM1: P < 0.05; C: P < 0.01) and fractional excretion of sodium decreased ( P < 0.01) in both groups. The urinary excretion rates of NO x were comparable during euglycaemia in DM1 and C. While in C, they significantly increased during Study 1 (period I: 382 ± 217 vs. period II: 515 ± 254 nmol/min; P < 0.01) and Study 2 (period I: 202.9 ± 176.8 vs. period II: 297.2 ± 267.5 nmol/min; P < 0.05) as a consequence of the water load, no changes were found in DM1. The urinary excretion of bradykinin was lower in DM1 compared with C (0.84 ± 0.68 vs. 1.20 ± 0.85 µg/min; P < 0.01) during euglycaemia; it was not affected by hyperglycaemia. There were no significant differences between DM1 and C and in cGMP urinary excretion rates following hyperglycaemia. Conclusion This study demonstrates that DM1 without renal haemodynamic alterations is associated with impaired renal sodium handling. Moreover, we did not find a relationship between the renal excretion rates of vasoactive mediators and sodium handling due to hyperglycaemia.