High-NaCl intake impairs dynamic autoregulation of renal blood flow in ANG II-infused rats

Abstract

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...

Blood pressure-renal blood flow relationships in conscious angiotensin II- and phenylephrine-infused rats

“…By contrast, the cellular mechanisms responsible for the apparently reduced myogenic responses after PE remain to be elucidated. In contrast to the myogenic response noted in the conscious rat (present studies) and in the conscious dog (47), Saeed et al (75) observed a reduced slope of gain reduction and diminished phase peak in anesthetized rats following 2 wk of ANG II at a higher dose (250 ng·kg Ϫ1 ·min…”

AT1 receptor-mediated augmentation of angiotensinogen, oxidative stress, and inflammation in ANG II-salt hypertension

“…Conversely, in salt-sensitive hypertension ROS-dependent enhancement of AGT may be involved in the development and progression of renal injury (15,26). Saeed et al (37) showed that ANG II-infused rats on a HS diet (ANG II-salt hypertension) developed impairment of dynamic renal blood flow autoregulation, which was attenuated by tempol (37). However, the unique effect of HS on the pathogenesis of ANG II-salt hypertension has not been established.…”

Effects of Endothelin Receptor Antagonists on Renal Hemodynamics in Angiotensin II-Infused Rats on High NaCl Intake

“…C7+C8, 80-120 minutes after start of drug administration) were subjected to power spectral and transfer function analyses using methods previously described in detail [21]. Data over the range of frequencies for the myogenic response (0.08-0.18) and the tubuloglomerular feedback (TGF) mechanism (0.03-0.06) were analysed [21,30,31].…”

“…C7+C8, 80-120 minutes after start of drug administration) were subjected to power spectral and transfer function analyses using methods previously described in detail [21]. Data over the range of frequencies for the myogenic response (0.08-0.18) and the tubuloglomerular feedback (TGF) mechanism (0.03-0.06) were analysed [21,30,31]. The slope of gain decrease in the frequency range of the myogenic response was determined by least squares fitting of the linear regression of gain decrease and the phase peak was estimated as the average phase value within the same frequency interval.…”

“…We have previously shown that rats with hypertension caused by chronic Ang IIinfusion and a high NaCl intake develop a marked increase in renovascular resistance and impairments in dynamic RBF autoregulation (RBFA) characterized by an abnormal myogenic response [21]. We hypothesized that ET-1 might contribute to these abnormalities in renal hemodynamics in this model.…”