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

Abstract

Aims/hypothesis In early type 1 diabetes mellitus, renal salt handling is dysregulated, so that the glomerular filtration rate becomes inversely proportional to salt intake. The salt paradox occurs in both humans and rats and, with low salt intake, results in diabetic hyperfiltration. We tested whether increased salt intake could reduce the susceptibility to injury of non-clipped kidneys in diabetic rats with pre-existing Goldblatt hypertension. Methods Male Long-Evans rats were made hypertensive and half were then made diabetic. Blood glucose was maintained at ∼20-25 mmol/l by insulin implants. One half of each received only the salt in normal chow (1% by weight) and the other half received added salt in drinking water to equal 2.7% by weight of food intake. Weekly 24 h blood pressure records were acquired by telemetry during the 4-month experiment. Results Systolic blood pressure was not affected by diabetes or increased salt intake, alone or together. Autoregulation was highly efficient in the non-clipped kidney of both intact and diabetic rats. Histological examination showed minor injury in the clipped kidney, which did not differ among groups. The non-clipped kidney showed extensive pressuredependent glomerular and vascular injury in both intact and diabetic rats. Conclusions/interpretation The relationship between pressure and injury was shifted toward lower blood pressure in diabetic rats, indicating that diabetes increased the susceptibility of the kidney to injury despite preservation of autoregulation. The increased susceptibility was not affected by high salt intake in the diabetic rats, thus disproving the hypothesis.

Physiological changes induced by salt intake in female Spontaneously Diabetic Torii‐Leprfa (SDT fatty) rat, a novel obese type 2 diabetic model

“…In other diabetic animal models, an increase of blood pressure after salt loading was reported in Goto Kakizaki (GK) rats, Streptozotocin-induced (STZ) rats, Zucker rats and Wistar fatty rats (Reddy & Kotchen 1992;Suzuki et al 1996;Carlson et al 2000;Hayashida et al 2001;Olearczyk et al 2009;Osorio et al 2009;Zhang et al 2009). On the other hand, blood pressure after salt loading did not change in Long-Evans rats or neonatal STZ rats (Iwase et al 1987;Sima et al 2012). In SDT fatty rats at 12 weeks of age, SBP was increased from 127 mmHg to 191 mmHg by salt intake for 8 weeks (Fig.…”

“…; Sima et al . ). In SDT fatty rats at 12 weeks of age, SBP was increased from 127 mmHg to 191 mmHg by salt intake for 8 weeks (Fig.…”

Renal Autoregulation in Health and Disease

“…The plateau phase of steadystate RBF autoregulation was maintained in one study (993), but the limit of autoregulation was shifted to a lower RPP in many studies (307,612,874,993,1365,1472), independent of PGs (1472). However, other studies reported that RBF autoregulation was impaired within hours of induction of hyperglycemia by STZ and persisted into the established phase of DM with attenuated myogenic (588) and MD-TGF responses (1509).…”

“…Dogs (1047) and some rats (705,707,1365,1566) with 2K,1C hypertension have maintained RBF and GFR autoregulation in the nonclipped kidney, although other studies in rats have reported weak autoregulation (1188,1404,1494) that was improved by NOS inhibition (1494). Blockade of AT 1 receptors in 2K,1C hypertensive rats did not affect RBF autoregulation in the nonclipped kidney but abolished GFR autoregulation (1566), presumably because of a reduced efferent arteriolar resistance.…”

“…The clipped kidney has a weak, or even nonexistent, autoregulation of RBF (705). The post-clip kidney and its blood vessels were protected from barotrauma, whereas there were extensive glomerular and vascular injuries in the contralateral nonclipped kidney (1365).…”