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

2010 ◽  
Vol 299 (5) ◽  
pp. R1142-R1149 ◽  
Author(s):  
Aso Saeed ◽  
Gerald F. DiBona ◽  
Niels Marcussen ◽  
Gregor Guron

The 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−1·min−1 sc) or saline vehicle (sham) for 14 days after which acute renal clearance experiments were performed during thiobutabarbital anesthesia. Rats ( n = 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 < 0.05). RBF in ANG II HNa was reduced vs. sham NNa and sham HNa (6.0 ± 0.3 vs. 7.9 ± 0.3 and 9.1 ± 0.3 ml·min−1·g kidney wt−1, P < 0.05). transfer function gain in ANG II HNa was significantly elevated in the frequency range of the MR (1.26 ± 0.50 dB, P < 0.05 vs. all other groups) and in the frequency range of the TGF (−0.02 ± 0.50 dB, P < 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.

2013 ◽  
Vol 305 (7) ◽  
pp. F1074-F1084 ◽  
Author(s):  
Aaron J. Polichnowski ◽  
Karen A. Griffin ◽  
Jianrui Long ◽  
Geoffrey A. Williamson ◽  
Anil K. Bidani

Chronic ANG II infusion in rodents is widely used as an experimental model of hypertension, yet very limited data are available describing the resulting blood pressure-renal blood flow (BP-RBF) relationships in conscious rats. Accordingly, male Sprague-Dawley rats ( n = 19) were instrumented for chronic measurements of BP (radiotelemetry) and RBF (Transonic Systems, Ithaca, NY). One week later, two or three separate 2-h recordings of BP and RBF were obtained in conscious rats at 24-h intervals, in addition to separate 24-h BP recordings. Rats were then administered either ANG II ( n = 11, 125 ng·kg−1·min−1) or phenylephrine (PE; n = 8, 50 mg·kg−1·day−1) as a control, ANG II-independent, pressor agent. Three days later the BP-RBF and 24-h BP recordings were repeated over several days. Despite similar increases in BP, PE led to significantly greater BP lability at the heart beat and very low frequency bandwidths. Conversely, ANG II, but not PE, caused significant renal vasoconstriction (a 62% increase in renal vascular resistance and a 21% decrease in RBF) and increased variability in BP-RBF relationships. Transfer function analysis of BP (input) and RBF (output) were consistent with a significant potentiation of the renal myogenic mechanism during ANG II administration, likely contributing, in part, to the exaggerated reductions in RBF during periods of BP elevations. We conclude that relatively equipressor doses of ANG II and PE lead to greatly different ambient BP profiles and effects on the renal vasculature when assessed in conscious rats. These data may have important implications regarding the pathogenesis of hypertension-induced injury in these models of hypertension.


2008 ◽  
Vol 295 (5) ◽  
pp. F1449-F1456 ◽  
Author(s):  
Tracy D. Bell ◽  
Gerald F. DiBona ◽  
Rachel Biemiller ◽  
Michael W. Brands

This study used 16 h/day measurement of renal blood flow (RBF) and arterial pressure (AP) to determine the role of nitric oxide (NO) in mediating the renal vasodilation caused by onset of type 1 diabetes. The AP and RBF power spectra were used to determine the autoregulatory efficiency of the renal vasculature. Rats were instrumented with artery and vein catheters and a Transonic flow probe on the left renal artery and were divided randomly into four groups: control (C), diabetes (D), control plus nitro-l-arginine methyl ester (l-NAME; CL), and diabetes plus l-NAME (DL). Mean AP averaged 90 ± 1 and 121 ± 1 mmHg in the D and DL groups, respectively, during the control period, and RBF averaged 5.9 ± 1.2 and 5.7 ± 0.7 ml/min, respectively. Respective C and CL groups were not different. Onset of diabetes (streptozotocin 40 mg/kg iv) in D rats increased RBF gradually, but it averaged 55% above control by day 14. In DL rats, on the other hand, RBF remained essentially constant, tracking with RBF in the nondiabetic C and CL groups for the 2-wk period. Diabetes did not change mean AP in any group. Transfer function analysis revealed impaired dynamic autoregulation of RBF overall, including the frequency range of tubuloglomerular feedback (TGF), and l-NAME completely prevented those changes as well. These data strongly support a role for NO in causing renal vasodilation in diabetes and suggest that an effect of NO to blunt RBF autoregulation may play an important role.


2009 ◽  
Vol 297 (1) ◽  
pp. F155-F162 ◽  
Author(s):  
K. L. Siu ◽  
B. Sung ◽  
W. A. Cupples ◽  
L. C. Moore ◽  
K. H. Chon

Detection of the low-frequency (LF; ∼0.01 Hz) component of renal blood flow, which is theorized to reflect the action of a third renal autoregulatory mechanism, has been difficult due to its slow dynamics. In this work, we used three different experimental approaches to detect the presence of the LF component of renal autoregulation using normotensive and spontaneously hypertensive rats (SHR), both anesthetized and unanesthetized. The first experimental approach utilized a blood pressure forcing in the form of a chirp, an oscillating perturbation with linearly increasing frequency, to elicit responses from the LF autoregulatory component in anesthetized normotensive rats. The second experimental approach involved collection and analysis of spontaneous blood flow fluctuation data from anesthetized normotensive rats and SHR to search for evidence of the LF component in the form of either amplitude or frequency modulation of the myogenic and tubuloglomerular feedback mechanisms. The third experiment used telemetric recordings of arterial pressure and renal blood flow from normotensive rats and SHR for the same purpose. Our transfer function analysis of chirp signal data yielded a resonant peak centered at 0.01 Hz that is greater than 0 dB, with the transfer function gain attenuated to lower than 0 dB at lower frequencies, which is a hallmark of autoregulation. Analysis of the data from the second experiments detected the presence of ∼0.01-Hz oscillations only with isoflurane, albeit at a weaker strength compared with telemetric recordings. With the third experimental approach, the strength of the LF component was significantly weaker in the SHR than in the normotensive rats. In summary, our detection via the amplitude modulation approach of interactions between the LF component and both tubuloglomerular feedback and the myogenic mechanism, with the LF component having an identical frequency to that of the resonant gain peak, provides evidence that 0.01-Hz oscillations may represent the third autoregulatory mechanism.


2016 ◽  
Vol 78 (5) ◽  
pp. 923-960 ◽  
Author(s):  
Ioannis Sgouralis ◽  
Vasileios Maroulas ◽  
Anita T. Layton

2008 ◽  
Vol 109 (4) ◽  
pp. 642-650 ◽  
Author(s):  
Yojiro Ogawa ◽  
Ken-ichi Iwasaki ◽  
Ken Aoki ◽  
Wakako Kojima ◽  
Jitsu Kato ◽  
...  

Background Dexmedetomidine, which is often used in intensive care units in patients with compromised circulation, might induce further severe decreases in cerebral blood flow (CBF) with temporal decreases in arterial pressure induced by various stimuli if dynamic cerebral autoregulation is not improved. Therefore, the authors hypothesized that dexmedetomidine strengthens dynamic cerebral autoregulation. Methods Fourteen healthy male subjects received placebo, low-dose dexmedetomidine (loading, 3 microg x kg(-1) x h(-1) for 10 min; maintenance, 0.2 microg x kg(-1) x h(-1) for 60 min), and high-dose dexmedetomidine (loading, 6 microg x kg(-1) x h(-1) for 10 min; maintenance, 0.4 microg x kg(-1) x h(-1) for 60 min) infusions in a randomized, double-blind, crossover study. After 70 min of drug administration, dynamic cerebral autoregulation was estimated by transfer function analysis between arterial pressure variability and CBF velocity variability, and the thigh cuff method. Results Compared with placebo, steady state CBF velocity and mean blood pressure significantly decreased during administration of dexmedetomidine. Transfer function gain in the very-low-frequency range increased and phase in the low-frequency range decreased significantly, suggesting alterations in dynamic cerebral autoregulation in lower frequency ranges. Moreover, the dynamic rate of regulation and percentage restoration in CBF velocity significantly decreased when a temporal decrease in arterial pressure was induced by thigh cuff release. Conclusion Contrary to the authors' hypothesis, the current results of two experimental analyses suggest together that dexmedetomidine weakens dynamic cerebral autoregulation and delays restoration in CBF velocity during conditions of decreased steady state CBF velocity. Therefore, dexmedetomidine may lead to further sustained reductions in CBF during temporal decreases in arterial pressure.


2001 ◽  
Vol 281 (1) ◽  
pp. R206-R212 ◽  
Author(s):  
Sarah-Jane Guild ◽  
Paul C. Austin ◽  
Michael Navakatikyan ◽  
John V. Ringwood ◽  
Simon C. Malpas

Blood pressure displays an oscillation at 0.1 Hz in humans that is well established to be due to oscillations in sympathetic nerve activity (SNA). However, the mechanisms that control the strength or frequency of this oscillation are poorly understood. The aim of the present study was to define the dynamic relationship between SNA and the vasculature. The sympathetic nerves to the kidney were electrically stimulated in six pentobarbital-sodium anesthetized rabbits, and the renal blood flow response was recorded. A pseudo-random binary sequence (PRBS) was applied to the renal nerves, which contains equal spectral power at frequencies in the range of interest (<1 Hz). Transfer function analysis revealed a complex system composed of low-pass filter characteristics but also with regions of constant gain. A model was developed that accounted for this relationship composed of a 2 zero/4 pole transfer function. Although the position of the poles and zeros varied among animals, the model structure was consistent. We also found the time delay between the stimulus and the RBF responses to be consistent among animals (mean 672 ± 22 ms). We propose that the identification of the precise relationship between SNA and renal blood flow (RBF) is a fundamental and necessary step toward understanding the interaction between SNA and other physiological mediators of RBF.


2016 ◽  
Vol 120 (12) ◽  
pp. 1434-1441 ◽  
Author(s):  
Sung-Moon Jeong ◽  
Seon-Ok Kim ◽  
Darren S. DeLorey ◽  
Tony G. Babb ◽  
Benjamin D. Levine ◽  
...  

Cerebral vasomotor reactivity (CVMR) and dynamic cerebral autoregulation (CA) are measured extensively in clinical and research studies. However, the relationship between these measurements of cerebrovascular function is not well understood. In this study, we measured changes in cerebral blood flow velocity (CBFV) and arterial blood pressure (BP) in response to stepwise increases in inspired CO2 concentrations of 3 and 6% to assess CVMR and dynamic CA in 13 healthy young adults [2 women, 32 ± 9 (SD) yr]. CVMR was assessed as percentage changes in CBFV (CVMRCBFV) or cerebrovascular conductance index (CVCi, CVMRCVCi) in response to hypercapnia. Dynamic CA was estimated by performing transfer function analysis between spontaneous oscillations in BP and CBFV. Steady-state CBFV and CVCi both increased exponentially during hypercapnia; CVMRCBFV and CVMRCVCi were greater at 6% (3.85 ± 0.90 and 2.45 ± 0.79%/mmHg) than at 3% CO2 (2.09 ± 1.47 and 0.21 ± 1.56%/mmHg, P = 0.009 and 0.005, respectively). Furthermore, CVMRCBFV was greater than CVMRCVCi during either 3 or 6% CO2 ( P = 0.017 and P < 0.001, respectively). Transfer function gain and coherence increased in the very low frequency range (0.02-0.07 Hz), and phase decreased in the low-frequency range (0.07–0.20 Hz) when breathing 6%, but not 3% CO2. There were no correlations between the measurements of CVMR and dynamic CA. These findings demonstrated influences of inspired CO2 concentrations on assessment of CVMR and dynamic CA. The lack of correlation between CVMR and dynamic CA suggests that cerebrovascular responses to changes in arterial CO2 and BP are mediated by distinct regulatory mechanisms.


2014 ◽  
Vol 36 (5) ◽  
pp. 563-575 ◽  
Author(s):  
Aisha S.S. Meel-van den Abeelen ◽  
Arenda H.E.A. van Beek ◽  
Cornelis H. Slump ◽  
Ronney B. Panerai ◽  
Jurgen A.H.R. Claassen

2004 ◽  
Vol 106 (2) ◽  
pp. 155-162 ◽  
Author(s):  
Penelope J. EAMES ◽  
John F. POTTER ◽  
Ronney B. PANERAI

Transfer function analysis has become one of the main techniques to study the dynamic relationship between cerebral blood flow and arterial blood pressure, but the influence of different respiratory rates on cerebral blood flow has not been fully investigated. In 14 healthy volunteers, middle cerebral artery blood flow velocity, recorded using transcranial Doppler ultrasound, non-invasive beat-to-beat Finapres blood pressure, ECG and end-tidal CO2 (PETCO2) levels were recorded with subjects resting supine and breathing spontaneously or at controlled rates of 6, 10 and 15 breaths/min. Transfer function analysis and impulse and step responses were computed at each respiratory rate. PETCO2 levels tended to fall slightly during paced respiration, especially at 15 breaths/min. Controlled breathing rates did not alter transfer function analysis in the frequency range below 0.08 Hz but, above this frequency, the coherence function contained significant peaks corresponding to the respiratory frequencies. The impulse response was similar at all breathing rates, but the step response was characteristic of more efficient autoregulation with reduced PETCO2 levels associated with increasing respiratory rate. The effects of breathing rate and rhythmicity and PETCO2 must be considered in studies of cerebral autoregulation.


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