scholarly journals Continuously measured renal blood flow does not increase in diabetes if nitric oxide synthesis is blocked

2008 ◽  
Vol 295 (5) ◽  
pp. F1449-F1456 ◽  
Author(s):  
Tracy D. Bell ◽  
Gerald F. DiBona ◽  
Rachel Biemiller ◽  
Michael W. Brands
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Renal Blood Flow ◽  
Function Analysis ◽  
Control Period ◽  
Power Spectra ◽  
Tubuloglomerular Feedback ◽  
Left Renal Artery ◽  
Renal Vasculature ◽  
Transfer Function Analysis

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.

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

2013 ◽  
Vol 305 (7) ◽  
pp. F1074-F1084 ◽  
Author(s):  
Aaron J. Polichnowski ◽  
Karen A. Griffin ◽  
Jianrui Long ◽  
Geoffrey A. Williamson ◽  
Anil K. Bidani
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Renal Blood Flow ◽  
Function Analysis ◽  
Heart Beat ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Renal Vasculature ◽  
Conscious Rats ◽  
Transfer Function Analysis

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.

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
Keyword(s):  
Blood Flow ◽  
Transfer Function ◽  
Renal Blood Flow ◽  
Function Analysis ◽  
Feedback Mechanism ◽  
Tubuloglomerular Feedback ◽  
Ang Ii ◽  
Frequency Range ◽  
Sprague Dawley ◽  
Transfer Function Analysis

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.

The step response: a method to characterize mechanisms of renal blood flow autoregulation

2003 ◽  
Vol 285 (4) ◽  
pp. F758-F764 ◽  
Author(s):  
T. Wronski ◽  
E. Seeliger ◽  
P. B. Persson ◽  
C. Forner ◽  
C. Fichtner ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Renal Perfusion ◽  
Oscillation Period ◽  
Tubuloglomerular Feedback ◽  
Step Response ◽  
Myogenic Response ◽  
Renal Vasculature ◽  
The Individual ◽  
Reported Data

Response of renal vasculature to changes in renal perfusion pressure (RPP) involves mechanisms with different frequency characteristics. Autoregulation of renal blood flow (RBF) is mediated by the rapid myogenic response, by the slower tubuloglomerular feedback (TGF) mechanism, and, possibly, by an even slower third mechanism. To evaluate the individual contribution of these mechanisms to RBF autoregulation, we analyzed the response of RBF to a step increase in RPP. In anesthetized rats, the suprarenal aorta was occluded for 30 s, and then the occlusion was released to induce a step increase in RPP. Three dampened oscillations were observed; their oscillation periods ranged from 9.5 to 13 s, from 34.2 to 38.6 s, and from 100.5 to 132.2 s, respectively. The two faster oscillations correspond with previously reported data on the myogenic mechanism and the TGF. In accordance, after furosemide, the amplitude of the intermediate oscillation was significantly reduced. Inhibition of nitric oxide synthesis by Nω-nitro-l-arginine methyl ester significantly increased the amplitude of the 10-s oscillation. It is concluded that the parameters of the dampened oscillations induced by the step increase in RPP reflect properties of autoregulatory mechanisms. The oscillation period characterizes the individual mechanism, the dampening is a measure for the stability of the regulation, and the square of the amplitudes characterizes the power of the respective mechanism. In addition to the myogenic response and the TGF, a third rather slow mechanism of RBF autoregulation exists.

scholarly journals Time-Dependent Autoregulation of Renal Blood Flow in Conscious Rats

2001 ◽  
Vol 12 (11) ◽  
pp. 2253-2262
Author(s):  
BERT FLEMMING ◽  
NICOLE ARENZ ◽  
ERDMANN SEELIGER ◽  
THOMAS WRONSKI ◽  
KATHARINA STEER ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Dynamic Properties ◽  
Rate Of Change ◽  
Tubuloglomerular Feedback ◽  
Operating Pressure ◽  
Renal Vasculature ◽  
Pressure Flow ◽  
Conscious Rats ◽  
Maximum Conductance

Abstract. Response of renal vasculature to changes in renal perfusion pressure (RPP) involves mechanisms with different frequency characteristics. Autoregulation of renal blood flow is mediated by a rapid myogenic response and a slower tubuloglomerular feedback mechanism. In 25 male conscious rats, ramp-shaped changes in RPP were induced to quantify dynamic properties of autoregulation. Decremental RPP ramps immediately followed by incremental ramps were made for four different rates of change, ranging from 0.118 to 1.056 mmHg/s. Renal blood flow and cortical and medullary fluxes were assessed, and the corresponding relative conductance values were calculated continuously. During RPP decrements, conductance increased. With increasing rate of change of RPP decrements, maximum conductance increased from 10% to 80%, as compared with control. This response, which indicates the magnitude of autoregulation, was more pronounced in cortical versus medullary vasculature. Pressure at maximum conductance decreased with increasing rate of change of RPP decrements from 88 to 72 mmHg. During RPP increments, dependence of maximum conductance changes on the rate of change was enhanced (-20 to 110% of control). Thus, a hysteresis-like asymmetry between RPP decrements and increments, a resetting of autoregulation, was observed, which in direction and magnitude depended on the rate of change and duration of RPP changes. In conclusion, renal vascular responses to changes in RPP are highly dependent on the dynamics of the error signal. Furthermore, the method presented allows differentiated stimulation of various static and dynamic components of pressure-flow relationship and, thus, a direct assessment of the magnitudes and operating pressure range of active mechanisms of pressure-flow relationships.

scholarly journals Dynamic characteristics and underlying mechanisms of renal blood flow autoregulation in the conscious dog

2001 ◽  
Vol 280 (6) ◽  
pp. F1062-F1071 ◽  
Author(s):  
Armin Just ◽  
Heimo Ehmke ◽  
Lira Toktomambetova ◽  
Hartmut R. Kirchheim
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Renal Blood Flow ◽  
Vascular Resistance ◽  
Time Course ◽  
External Iliac Artery ◽  
Tubuloglomerular Feedback ◽  
Step Response ◽  
Myogenic Response ◽  
Pressure Step

The time course of the autoregulatory response of renal blood flow (RBF) to a step increase in renal arterial pressure (RAP) was studied in conscious dogs. After RAP was reduced to 50 mmHg for 60 s, renal vascular resistance (RVR) decreased by 50%. When RAP was suddenly increased again, RVR returned to baseline with a characteristic time course (control; n = 15): within the first 10 s, it rose rapidly to 70% of baseline ( response 1), thus already comprising 40% of the total RVR response. Thereafter, it increased at a much slower rate until it started to rise rapidly again at 20–30 s after the pressure step ( response 2). After passing an overshoot of 117% at 43 s, RVR returned to baseline values. Similar responses were observed after RAP reduction for 5 min or after complete occlusions for 60 s. When tubuloglomerular feedback (TGF) was inhibited by furosemide (40 mg iv, n = 12), response 1 was enhanced, providing 60% of the total response, whereas response 2 was completely abolished. Instead, RVR slowly rose to reach the baseline at 60 s ( response 3). The same pattern was observed when furosemide was given at a much higher dose (>600 mg iv; n = 6) or in combination with clamping of the plasma levels of nitric oxide ( n = 6). In contrast to RVR, vascular resistance in the external iliac artery after a 60-s complete occlusion started to rise with a delay of 4 s and returned to baseline within 30 s. It is concluded that, in addition to the myogenic response and the TGF, a third regulatory mechanism significantly contributes to RBF autoregulation, independently of nitric oxide. The three mechanisms contribute about equally to resting RVR. The myogenic response is faster in the kidney than in the hindlimb.

Localization and regulation of endothelial NO synthase mRNA expression in rat kidney

1994 ◽  
Vol 267 (2) ◽  
pp. F296-F302 ◽  
Author(s):  
K. Ujiie ◽  
J. Yuen ◽  
L. Hogarth ◽  
R. Danziger ◽  
R. A. Star
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Filtration Rate ◽  
Competitive Inhibition ◽  
Rat Kidney ◽  
Oral Treatment ◽  
Renal Vasculature

Nitric oxide (NO) has effects on renal blood flow, glomerular filtration rate, renin secretion, and renal sodium excretion. Four isoforms of nitric oxide synthase (NOS) have been cloned to date. However, the molecular identity of NOS present in the renal vasculature is unknown. Endothelial NOS (NOS-III) is regulated both acutely by cell calcium and chronically by shear stress. To determine if renal blood vessels and the glomerulus express NOS-III mRNA, we used degenerate polymerase chain reaction (PCR) to clone a portion of rat NOS-III. We then assayed NOS-III mRNA in microdissected renal structures by reverse transcriptase-PCR. NOS-III mRNA was expressed at high levels in glomeruli, arcuate vessels, and interlobular artery/afferent arterioles. NOS-III mRNA was detected inconsistently in proximal tubules, thick ascending limbs, and cortical and inner medullary collecting ducts. Previous studies have shown that chronic oral treatment with the NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) decreases NO synthesis and causes hypertension. To determine if the systemic blockade occurs only by competitive inhibition, we determined the effect of L-NAME on glomerular NOS-III mRNA. L-NAME administration (5 days) decreased NOS-III mRNA in the glomerulus to 25 +/- 12% of control levels. We conclude that endothelial NOS-III mRNA is preferentially expressed in the glomerulus and renal vasculature, where it can modulate renal blood flow and glomerular filtration rate. Furthermore, glomerular NOS-III may be modulated at the level of mRNA abundance in vivo by systemic L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency-dependent modulation of renal blood flow by renal nerve activity in conscious rabbits

1997 ◽  
Vol 273 (2) ◽  
pp. R597-R608 ◽  
Author(s):  
B. J. Janssen ◽  
S. C. Malpas ◽  
S. L. Burke ◽  
G. A. Head
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
High Frequency ◽  
Left Renal Artery ◽  
Renal Vasculature ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Moderate Hypoxia ◽  
Cardiac Frequency ◽  
Conscious Rabbits

To examine the influence of the various frequency components of renal sympathetic nerve activity (RSNA) on renal blood flow (RBF) dynamics, a Doppler flow probe and renal nerve electrode were implanted on the left renal artery of 10 rabbits. Experiments were performed 4-9 days after surgery. Physiological changes in RSNA were induced by subjecting the rabbits to periods of breathing hypoxic gas mixtures. Signals were sampled at 1 kHz and analyzed by spectral analysis. During moderate hypoxia (arterial PO2 = 44 +/- 1 mmHg), arterial pressure and heart rate did not change, averaged RSNA increased by 90 +/- 7%, and RBF fell by 18 +/- 3%. In a separate group of renal-denervated rabbits (n = 6), no changes in RBF occurred during hypoxia. In intact rabbits, 53 +/- 4% of spectral density power of RSNA was found at the cardiac frequency and the remainder was predominantly coupled to respiration (approximately 0.9 Hz). During moderate hypoxia the amplitude of the RSNA oscillations increased 17 +/- 6 times at the cardiac frequency and 10 +/- 3 times at the respiration-related frequency. Modulation of RBF variability by the fluctuations of RSNA at the cardiac- and respiration-related frequency was, however, small. The normalized transfer gain between RSNA and RBF was approximately 0.1 at > 0.5 Hz. This means that, at > 0.5 Hz, maximally 10% of the amplitude of the RSNA oscillations is transmitted to corresponding RBF fluctuations. These transfer properties did not change during hypoxia. At < 0.5 Hz the transfer gain between RSNA and RBF increased. During moderate hypoxia, 0.3-Hz coherent oscillations of RSNA and RBF were found. In renal-denervated rabbits, 0.3-Hz oscillations in RBF were absent. Thus the renal vasculature was able to follow relatively low-frequency (< 0.5-Hz) fluctuations of RSNA and responded with corresponding oscillations in RBF. In contrast, the renal vasculature responded with increased constriction at the high-frequency (> 0.5-Hz) fluctuations of RSNA. These findings suggest that, in conscious rabbits, high-frequency oscillations of RSNA contribute to the vasoconstrictor tone, whereas the lower frequencies of RSNA contribute to the variability of RBF.

scholarly journals Detection of low-frequency oscillations in renal blood flow

2009 ◽  
Vol 297 (1) ◽  
pp. F155-F162 ◽  
Author(s):  
K. L. Siu ◽  
B. Sung ◽  
W. A. Cupples ◽  
L. C. Moore ◽  
K. H. Chon
Keyword(s):  
Blood Flow ◽  
Transfer Function ◽  
Renal Blood Flow ◽  
Experimental Approach ◽  
Low Frequency ◽  
Tubuloglomerular Feedback ◽  
Resonant Peak ◽  
The Third ◽  
Transfer Function Analysis ◽  
Autoregulatory Mechanism

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.

scholarly journals Renal nerves dynamically regulate renal blood flow in conscious, healthy rabbits

2016 ◽  
Vol 310 (2) ◽  
pp. R156-R166 ◽  
Author(s):  
Alicia M. Schiller ◽  
Peter R. Pellegrino ◽  
Irving H. Zucker
Keyword(s):  
Blood Flow ◽  
Phase Shift ◽  
Renal Blood Flow ◽  
Renal Denervation ◽  
Function Analysis ◽  
Extracellular Fluid ◽  
Low Frequency ◽  
Renal Nerves ◽  
Physiological Regulation ◽  
Transfer Function Analysis

Despite significant clinical interest in renal denervation as a therapy, the role of the renal nerves in the physiological regulation of renal blood flow (RBF) remains debated. We hypothesized that the renal nerves physiologically regulate beat-to-beat RBF variability (RBFV). This was tested in chronically instrumented, healthy rabbits that underwent either bilateral surgical renal denervation (DDNx) or a sham denervation procedure (INV). Artifact-free segments of RBF and arterial pressure (AP) from calmly resting, conscious rabbits were used to extract RBFV and AP variability for time-domain, frequency-domain, and nonlinear analysis. Whereas steady-state measures of RBF, AP, and heart rate did not statistically differ between groups, DDNx rabbits had greater RBFV than INV rabbits. AP-RBF transfer function analysis showed greater admittance gain in DDNx rabbits than in INV rabbits, particularly in the low-frequency (LF) range where systemic sympathetic vasomotion gives rise to AP oscillations. In the LF range, INV rabbits exhibited a negative AP-RBF phase shift and low coherence, consistent with the presence of an active control system. Neither of these features were present in the LF range of DDNx rabbits, which showed no phase shift and high coherence, consistent with a passive, Ohm's law pressure-flow relationship. Renal denervation did not significantly affect nonlinear RBFV measures of chaos, self-affinity, or complexity, nor did it significantly affect glomerular filtration rate or extracellular fluid volume. Cumulatively, these data suggest that the renal nerves mediate LF renal sympathetic vasomotion, which buffers RBF from LF AP oscillations in conscious, healthy rabbits.

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