Journal
NEPHROLOGY DIALYSIS TRANSPLANTATION
Volume 25, Issue 9, Pages 2945-2953Publisher
OXFORD UNIV PRESS
DOI: 10.1093/ndt/gfq150
Keywords
blood pressure; dopamine; glycaemic control; natriuresis; streptozotocin and type 1 diabetes mellitus
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Funding
- Fundacao para a Ciencia e Tecnologia/FEDER [PIC/IC/83029/2007, SFRH/BD/18869/2004, SFRH/BPD/21782/2005]
- Fundação para a Ciência e a Tecnologia [SFRH/BPD/21782/2005, PIC/IC/83029/2007, SFRH/BD/18869/2004] Funding Source: FCT
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Background. It was demonstrated in streptozotocin (STZ)-induced diabetic rats that the D-1 receptor agonist failed to promote sodium excretion as a result of reduced renal D-1 receptor expression and decreased receptor G protein coupling. The present study examined the influence of glycaemic control with insulin on the renal D-1 receptor dysfunction in STZ-induced type 1 diabetes. Methods. Renal function, blood pressure, the natriuretic response to 5% volume expansion (VE) and the effects of the D-1 receptor agonist fenoldopam on natriuresis and on Na+/K+-ATPase activity in renal tubules were evaluated in uninephrectomized and sham-operated Wistar rats treated with STZ and compared with controls and STZ-treated rats made euglycaemic with insulin. D-1 receptor immunohistochemistry and protein abundance by western blot were also determined in all groups. Results. Treatment of sham and uninephrectomized rats with STZ caused a 4-fold increase in glucose plasma levels compared to controls and euglycaemic diabetic rats. A blunted natriuretic response to VE was observed in both sham and uninephrectomized hyperglycaemic diabetic rats, and this was accompanied by failure of fenoldopam to increase natriuresis and to inhibit renal Na+/K+-ATPase activity. In contrast, in both sham and uninephrectomized euglycaemic diabetic rats, the natriuretic response to VE, the fenoldopam-induced natriuresis and the accompanied inhibition of Na+/K+-ATPase activity were similar to those of the corresponding controls. D-1 receptor immuno-detection and protein abundance were reduced in hyperglycaemic diabetic rats, but not in euglycaemic diabetic animals. Conclusions. We conclude that the renal expression and natriuretic response to D-1 receptor activation is compromised in both sham and uninephrectomized rats with STZ-induced diabetes. These abnormalities were prevented by lowering glucose blood levels with insulin, thus providing evidence for the involvement of hyperglycaemia in the disturbances that underlie the compromised dopamine-sensitive natriuresis and increase of blood pressure in type 1 diabetes.
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