Continuously measured renal blood flow does not increase in diabetes if nitric oxide synthesis is blocked

Abstract

This study used 16 h/day measurement of renal blood flow (RBF) and arterial pressure (AP) to determine the role of nitric oxide (NO) in mediating the renal vasodilation caused by onset of type 1 diabetes. The AP and RBF power spectra were used to determine the autoregulatory efficiency of the renal vasculature. Rats were instrumented with artery and vein catheters and a Transonic flow probe on the left renal artery and were divided randomly into four groups: control (C), diabetes (D), control plus nitro-L-arginine methyl ester (L-NAME; CL), and diabetes plus L-NAME (DL). Mean AP averaged 90 +/- 1 and 121 +/- 1 mmHg in the D and DL groups, respectively, during the control period, and RBF averaged 5.9 +/- 1.2 and 5.7 +/- 0.7 ml/min, respectively. Respective C and CL groups were not different. Onset of diabetes (streptozotocin 40 mg/kg iv) in D rats increased RBF gradually, but it averaged 55% above control by day 14. In DL rats, on the other hand, RBF remained essentially constant, tracking with RBF in the nondiabetic C and CL groups for the 2-wk period. Diabetes did not change mean AP in any group. Transfer function analysis revealed impaired dynamic autoregulation of RBF overall, including the frequency range of tubuloglomerular feedback (TGF), and L-NAME completely prevented those changes as well. These data strongly support a role for NO in causing renal vasodilation in diabetes and suggest that an effect of NO to blunt RBF autoregulation may play an important role.

Increased susceptibility to hypertensive renal disease in streptozotocin-treated diabetic rats is not modulated by salt intake

“…Very different dependency of RBF dynamics on nitric oxide generation is seen in early and established diabetes. One week after STZ, RBF dynamics were essentially pressure-passive, but active myogenic and TG feedback dynamics were restored by NOS inhibition, consistent with a dominant role for nitric oxide at this time [49]. In contrast, strong myogenic and TG feedback dynamics were seen 4 weeks after STZ and were not modulated by NOS inhibition [16].…”

Insulin Resistance in Kidney Disease: Is There a Distinct Role Separate from That of Diabetes or Obesity

“…These effects occur in parallel to a reduction in glucose uptake and utilization. In the context of renal glomerular hemodynamics, this impairment in insulin metabolic signaling and reduction in PI3K/Akt due to insulin resistance promotes reduced NO production and associated impairment of tubuloglomerular feedback, hyperfiltration, and sodium retention [25,26,27,28,29,30]. Tubuloglomerular feedback is the mechanism by which the kidney autoregulates renal blood flow and glomerular filtration.…”

Hyperfiltration and effect of nitric oxide inhibition on renal and endothelial function in humans with uncomplicated type 1 diabetes mellitus

“…Conversely, inducible NOS (iNOS) expression studies have demonstrated less consistent results (32). Therefore, it is generally accepted that eNOS and nNOS expression are upregulated in experimental models of DM leading to increased NO bioactivity, particularly in the early adaptive stages, but the functional significance of this upregulation in humans has not been fully elucidated (3).…”