Salt-resistant blood pressure and salt-sensitive renal autoregulation in chronic streptozotocin diabetes

Abstract

Hyperfiltration occurs in early type 1 diabetes mellitus in both rats and humans. It results from afferent vasodilation and thus may impair stabilization of glomerular capillary pressure by autoregulation. It is inversely related to dietary salt intake, the "salt paradox." Restoration of normal glomerular filtration rate (GFR) involves increased preglomerular resistance, probably mediated by tubuloglomerular feedback (TGF). To begin to test whether the salt paradox has pathogenic significance, we compared intact vs. diabetic (streptozotocin) Long-Evans rats with normal and increased salt intake, 1 and approximately 3% by weight of food eaten, respectively. Weekly 24-h blood pressure records were acquired by telemetry before and during diabetes. Blood glucose was maintained at approximately 20 mmol/l by insulin implants. GFR was significantly elevated only in diabetic rats on normal salt intake, confirming diabetic hyperfiltration and the salt paradox. Renal blood flow dynamics show strong contributions to autoregulation by both TGF and the myogenic mechanism and were not impaired by diabetes or by increased salt intake. Separately, systolic pressure was not elevated in diabetic rats at any time during 12 wk with normal or high salt intake. Autoregulation was effective in all groups, and the diabetic-normal salt group showed significantly improved autoregulation at low perfusion pressures. Histological examination revealed very minor glomerulosclerosis and modest mesangial expansion, although neither was diagnostic of diabetes. Periodic acid-Schiff-positive droplets found in distal tubules and collecting duct segments were diagnostic of diabetic kidneys. Biologically significant effects attributable to increased salt intake were abrogation of hyperfiltration and of the left shift in autoregulation in diabetic rats.

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

“…Salt-sensitive hypertension is well known in some humans and other animals [22], and a high incidence of salt sensitivity of BP has been suggested in the evolution of diabetes mellitus [23], although this too is not a universal finding [24]. Therefore, we first showed that increasing salt intake from 1% to 3% by weight of food eaten did not affect BP in intact rats or in poorly controlled type 1 diabetes [16]. The salt paradox was confirmed, but since no pathological changes were seen, that study did not test whether increasing salt intake affected susceptibility to nephropathy in type 1 diabetes.…”

“…Data were acquired at 1,000 Hz in 10 s bursts every 2 min. Systolic BP is reported in order to maintain consistency with previous studies in the literature [7,14,16] and because it is more closely correlated with organ damage than mean or diastolic BP [10]. Body weight and blood glucose were measured twice weekly in all animals; blood samples were acquired from the tail of conscious, unrestrained rats.…”

“…A PA11-C40 pressure telemeter (Data Sciences International, St Paul, MN, USA) was implanted s.c. in the left flank and secured by a purse string suture. The 10 cm cannula was inserted in the femoral artery and advanced into the aorta to the level of the renal arteries, leaving slack to accommodate growth [16,27]. After recovery (∼2 weeks) and acquisition of a control record, all rats were subjected to the 2K1C procedure [27].…”

“…Autoregulation At the end of the study, renal blood flow (RBF) and autoregulation were assessed in the left, nonclipped kidney [16,29]. Briefly, after anaesthesia and cannulation of the trachea, cannulae were placed in a femoral artery to measure perfusion pressure and in a femoral vein for infusions.…”

“…It is often considered that autoregulation is impaired in diabetes, and diabetic hyperfiltration has been attributed to enhanced transmission of systemic pressure to glomeruli [2,12,13]. However, efficient autoregulation has also been reported in diabetes [7,[14][15][16], and the literature has been described as contradictory [14,17].…”