High-NaCl diet impairs dynamic renal blood flow autoregulation in rats with adenine-induced chronic renal failure

Abstract

This study examined the effects of 2 wk of high-NaCl diet on kidney function and dynamic renal blood flow autoregulation (RBFA) in rats with adenine-induced chronic renal failure (ACRF). Male Sprague-Dawley rats received either chow containing adenine or were pair-fed an identical diet without adenine (controls). After 10 wk, rats were randomized to either remain on the same diet (0.6% NaCl) or to be switched to high 4% NaCl chow. Two weeks after randomization, renal clearance experiments were performed under isoflurane anesthesia and dynamic RBFA, baroreflex sensitivity (BRS), systolic arterial pressure variability (SAPV), and heart rate variability were assessed by spectral analytical techniques. Rats with ACRF showed marked reductions in glomerular filtration rate and renal blood flow (RBF), whereas mean arterial pressure and SAPV were significantly elevated. In addition, spontaneous BRS was reduced by ∼50% in ACRF animals. High-NaCl diet significantly increased transfer function fractional gain values between arterial pressure and RBF in the frequency range of the myogenic response (0.06-0.09 Hz) only in ACRF animals (0.3 ± 4.0 vs. -4.4 ± 3.8 dB; P < 0.05). Similarly, a high-NaCl diet significantly increased SAPV in the low-frequency range only in ACRF animals. To conclude, a 2-wk period of a high-NaCl diet in ACRF rats significantly impaired dynamic RBFA in the frequency range of the myogenic response and increased SAPV in the low-frequency range. These abnormalities may increase the susceptibility to hypertensive end-organ injury and progressive renal failure by facilitating pressure transmission to the microvasculature.

High-NaCl Diet Aggravates Cardiac Injury in Rats with Adenine-Induced Chronic Renal Failure and Increases Serum Troponin T Levels

“…Complete data on renal hemodynamics, kidney function, and plasma electrolytes have previously been published [14]. …”

“…Chronic renal failure was induced by feeding the animals with chow containing adenine as previously described [12,13,14]. At the beginning of the study, the animals were provided with standard pelleted rat chow containing adenine (group ACRF, n = 20) or identical chow without adenine [pair-fed controls (C), n = 19].…”

“…Chow intake was measured throughout the study, and as a consequence of our pair-feeding protocol there were no differences between groups in chow intake. Data on kidney function and renal hemodynamics from acute experiments have previously been published [14]. …”

“…In brief, the rats were anesthetized with isoflurane (Pharmacia & Upjohn, Stockholm, Sweden) and prepared for renal clearance experiments as described [14]. Isoflurane mixed with air was administered by spontaneous breathing using an isoflurane vaporizer (Univentor-1200; AgnTho's, Lidingö, Sweden).…”

“…Hence, we have established a rat model of adenine-induced chronic renal failure (ACRF) which bears close resemblance to the uremic syndrome in patients [12,13,14]. In this well-characterized model, rats develop severe renal failure and GFR values are approximately 10% of those in controls [12,13,14]. …”