aim of this study was to investigate dynamic autoregulation of renal blood flow (RBF) in ANG II-infused rats and the influence of high-NaCl intake. Sprague-Dawley rats received ANG II (250 ng·kg Ϫ1 ·min Ϫ1 sc) or saline vehicle (sham) for 14 days after which acute renal clearance experiments were performed during thiobutabarbital anesthesia. Rats (n ϭ 8 -10 per group) were either on a normal (NNa; 0.4% NaCl)-or high (HNa; 8% NaCl)-NaCl diet. Separate groups were treated with 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol; 1 M in drinking water). Transfer function analysis from arterial pressure to RBF in the frequency domain was used to examine the myogenic response (MR; 0.06 -0.09 Hz) and the tubuloglomerular feedback mechanism (TGF; 0.03-0.06 Hz). MAP was elevated in ANG II-infused rats compared with sham groups (P Ͻ 0.05). RBF in ANG II HNa was reduced vs. sham NNa and sham HNa (6.0 Ϯ 0.3 vs. 7.9 Ϯ 0.3 and 9.1 Ϯ 0.3 ml·min Ϫ1 ·g kidney wt Ϫ1 , P Ͻ 0.05). transfer function gain in ANG II HNa was significantly elevated in the frequency range of the MR (1.26 Ϯ 0.50 dB, P Ͻ 0.05 vs. all other groups) and in the frequency range of the TGF (Ϫ0.02 Ϯ 0.50 dB, P Ͻ 0.05 vs. sham NNa and sham HNa). Gain values in the frequency range of the MR and TGF were significantly reduced by tempol in ANG II-infused rats on HNa diet. In summary, the MR and TGF components of RBF autoregulation were impaired in ANG II HNa, and these abnormalities were attenuated by tempol, suggesting a pathogenetic role for superoxide in the impaired RBF autoregulatory response. tubuloglomerular feedback; superoxide; myogenic response HYPERTENSION IS A COMMON CAUSE of kidney injury and end-stage renal disease and accelerates loss of kidney function in patients with chronic kidney disease, regardless of the underlying etiology (19). However, the risk of renal injury is variable, and the pathophysiological mechanisms by which hypertension causes renal parenchymal injury are complex and incompletely understood (5,13,27,28,34). The renal blood flow (RBF) autoregulatory response, mediated mainly by the myogenic response (MR) and the tubuloglomerular feedback mechanism (TGF), stabilizes RBF and glomerular filtration rate (GFR), despite wide variations in arterial blood pressure (AP) (9, 23). RBF autoregulation (RBFA) may also serve a protective function, particularly in hypertension, by preventing transmission of systemic AP to the glomerular capillaries (2, 28). A role for autoregulatory capacity as a determinant of vulnerability to renal injury has been suggested in the 5/6 renal ablation model in rats (4) and in genetic models characterized by impaired RBFA (37, 38). In addition, treatment with dihydropyridine calcium channel blockers, which interfere with RBFA by impairing the MR, has been shown to increase the susceptibility to hypertensive glomerular injury in rats subjected to 5/6 nephrectomy (17).Increased dietary NaCl has been shown to accelerate renal injury in hypertension (1,5,32). However, the pathophysiological mechanisms by which inc...
ACCmax and AImax provide similar, good diagnostic accuracy in the detection of a haemodynamically significant RAS, even in patients with markedly reduced glomerular filtration rate. Presumably, the lack of superiority of the novel index AImax could be explained by a highly homogenous methodological approach in the present single-centre study.
The first goal of this study was to measure the oxidative stress (OS) and relate it to lipoprotein variables in 35 renal patients before dialysis (CKD), 37 on hemodialysis (HD) and 63 healthy subjects. The method for OS was based on the ratio of cholesteryl esters (CE) containing C18/C16 fatty acids (R2) measured by gas chromatography (GC) which is a simple, direct, rapid and reliable procedure. The second goal was to investigate and identify a triacylglycerol peak on GC, referred to as TG48 (48 represents the sum of the three fatty acids carbon chain lengths) which was markedly increased in renal patients compared to healthy controls. We measured TG48 in patients and controls. Mass spectrometry (MS) and MS twice in tandem were used to analyze the fatty acid composition of TG48. MS showed that TG48 was abundant in saturated fatty acids (SFAs) that were known for their pro-inflammatory property. TG48 was significantly and inversely correlated with OS. Renal patients were characterized by higher OS and inflammation than healthy subjects. Inflammation correlated strongly with TG, VLDL-cholesterol, apolipoprotein (apo) C-III and apoC-III bound to apoB-containing lipoproteins, but not with either total cholesterol or LDL-cholesterol.In conclusion, we have discovered a new inflammatory factor, TG48. It is characterized with TG rich in saturated fatty acids. Renal patients have increased TG48 than healthy controls.
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.
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