Abnormalities in the renal and vascular responses to LBNP in humans with early diabetes

Plasma atrial natriuretic factor (ANF) concentrations are increased in subjects with insulin-dependent diabetes mellitus (IDDM). A potential contribution of ANF to the maintenance of abnormalities in renal hemodynamic function has been considered but not proven in human diabetic subjects. The aim of these experiments was to determine the response of renal blood flow (RBF), glomerular filtration rate (GFR), filtration fraction (FF), and urinary sodium excretion (U(Na)V) to a reduction of plasma ANF concentrations induced by application of nonhypotensive lower body negative pressure (LBNP) in a group of subjects with early, uncomplicated, well-controlled IDDM compared with control subjects. Baseline supine measurements before LBNP revealed the diabetic subjects to have a significantly higher plasma ANF (31 ± 2 vs. 24 ± 2 pg/ml, P = 0.05). GFR tended to be higher (118 ± 11 vs. 104 ± 9 ml/min) and U(Na)V tended to be depressed (188 ± 25 vs. 240 ± 25 μmol/min) despite equal sodium intake, but not significantly so. In addition IDDM subjects exhibited significantly lower baseline plasma norepinephrine (PNE) concentrations (0.91 ± 0.20 vs. 1.60 ± 0.2 nmol/l, P = 0.03). Forearm vascular resistance (FVR) was not significantly different between the two groups (29 ± 5 vs. 33 ± 5 units). LBNP induced comparable decreases in ANF and central venous pressure (CVP) in both groups. The anticipated renal response to ANF reduction (declines in GFR, FF, and U(Na)V) occurred only in the normal control group. The percent decline in GFR (11% vs. 34.5%, P = 0.01) was markedly attenuated in IDDM subjects. The expected reflexive increase in PNE and FVR also did not occur in IDDM subjects. We conclude that increased plasma ANF concentrations do not play a major role in the modulation of GFR in the early stages of diabetes. Our data point to disturbances in adrenergic function that may contribute to the observed renal and vasoregulatory abnormalities.