Renal Vascular Endothelial Function in Hypertensive Patients With Type 2 Diabetes Mellitus

Background

Basal nitric oxide (NO) activity has a pivotal role in the regulation of glomerular hemodynamics, and in animal experiments, its alteration has been associated with morphological changes characteristic of diabetic nephropathy.

Study Design

Prospective observational-study during a mean follow-up of 2.1 years.

Setting & Participants

66 hypertensive patients (aged 30 to 80 years) with type 2 diabetes and estimated glomerular filtration rate (GFR) greater than 80 mL/min/1.73 m² with normoalbuminuria or microalbuminuria.

Predictor

Mean arterial pressure during follow-up during treatment with telmisartan or ramipril for 9 weeks, followed by treatment according to the discretion of the individual primary care physician.

Outcomes & Measurements

Renal vascular resistance, renal plasma flow, GFR, and change in renal plasma flow in response to infusion of the NO synthase inhibitor N-monomethyl-l-arginine as an indicator of basal NO activity in the renal vasculature.

Results

50 of 66 patients could be reexamined. At follow-up, mean arterial pressure decreased from 106 ± 9.1 to 100 ± 11 mm Hg (P < 0.001). Body mass index and hemoglobin A_1c levels were unaltered. Renal vascular resistance decreased (from 128 ± 44 to 103 ± 30 mm Hg/mL/min/1.73 m²; P < 0.001), renal plasma flow increased (from 490 ± 133 to 589 ± 154 mL/min/1.73 m²; P < 0.001), and GFR did not change (113 ± 22 versus 116 ± 26 mL/min/1.73 m²; P = 0.4) during follow-up. The decrease in renal plasma flow in response to N-monomethyl-l-arginine infusion was more pronounced at follow-up (−56.7 ± 39 versus −73.4 ± 48 mL/min/1.73 m²; P = 0.02), indicating improved basal NO activity. After adjustment for possible confounders, patients with a marked decrease in mean arterial pressure showed more improved basal NO activity during follow-up than those with a less pronounced decrease in mean arterial pressure (P = 0.04).

Limitations

Patients were treated according to the discretion of the individual primary care physician.

Conclusions

During follow-up, renal vascular resistance, renal plasma flow, and renal endothelial function (indicated by basal NO activity) improved. Better blood pressure control was associated with improved endothelial function of the renal vasculature, thereby potentially mediating the changes in renal hemodynamics.

Index Words: Prospective study, type 2 diabetes, basal nitric oxide activity, renal vasculature