Effect of early stage of experimental diabetes on vascular functions in isolated perfused kidneys.

The present study investigates the renal vascular responsiveness to vasoactive agents in diabetic rats which present an early stage of renal failure. Adult male Wistar rats were administered alloxan (150 mg kg(-1), s.c.). Seven days later the right kidneys were isolated and perfused. Renal perfusion pressure was measured continuously. Concentration-response curves were plotted for noradrenaline (NA), sodium nitroprusside (SNP) and carbachol. In basal conditions, kidneys from diabetic rats presented a decreased vascular resistance compared with those from control rats. The vasoconstrictor response to NA showed decreased EC50 values in preparations from diabetic rats compared with control ones (EC50 nmols, control: 2.03 +/- 0.44, n = 8; diabetic: 0.84+/-0.18, n = 6, P < 0.05). This enhanced sensitivity to NA could be in line with the decreased glomerular filtration rate and cortical renal plasma flow previously described in vivo in our laboratory (Garcia, Girardi, Ochoa, Torres & Elias, 1998). Vasoconstrictor responses to phenylephrine were not however, different between diabetic and control rat kidneys. This suggests that the increased sensitivity to NA was due to impaired neuronal uptake since phenylephrine is not a substrate for neuronal uptake. After precontraction with phenylephrine, both endothelium-dependent (carbachol) and endothelium independent (SNP) vasodilator agents caused similar response in the preparations taken from the two groups of animals. So, the enhanced sensitivity to NA is not associated with a deficient dilator responsiveness of the renal vasculature. The vasodilator response to carbachol was the same in absence or presence of L-arginine in the perfusate, suggesting no alteration in its availability at this stage of diabetes. Diabetic animals showed increased plasma level of fructosamine and glycosylated haemoglobin (Hb A1c), indicating the presence of early glycated products at this stage of diabetes, which could be involved in a possible structural alteration of the vessels.