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

Just, Armin; Ehmke, Heimo; Toktomambetova, Lira; Kirchheim, H. R.

doi:10.1152/ajprenal.2001.280.6.f1062

Cited by 45 publications

(87 citation statements)

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“…Dynamic responses indicate that the secondary phase (between approximately 5 and approximately 25 s) is affected most markedly in mice lacking Cx40. This component has been shown to reflect the action of classical TGF in dogs, 29 rats, 30 and mice. 16 The present data therefore indicate that classical TGF is severely attenuated in the absence of Cx40.…”

Section: Discussionmentioning

confidence: 99%

Connexin 40 Mediates the Tubuloglomerular Feedback Contribution to Renal Blood Flow Autoregulation

Just

Kurtz

Wit

et al. 2009

Journal of the American Society of Nephrology

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Connexins are important in vascular development and function. Connexin 40 (Cx40), which plays a predominant role in the formation of gap junctions in the vasculature, participates in the autoregulation of renal blood flow (RBF), but the underlying mechanisms are unknown. Here, Cx40-deficient mice (Cx40-ko) had impaired steady-state autoregulation to a sudden step increase in renal perfusion pressure. Analysis of the mechanisms underlying this derangement suggested that a marked reduction in tubuloglomerular feedback (TGF) in Cx40-ko mice was responsible. In transgenic mice with Cx40 replaced by Cx45, steady-state autoregulation and TGF were weaker than those in wild-type mice but stronger than those in Cx40-ko mice. N-Nitro-L-arginine-methyl-ester (L-NAME) augmented the myogenic response similarly in all genotypes, leaving autoregulation impaired in transgenic animals. The responses of renovascular resistance and arterial pressure to norepinephrine and acetylcholine were similar in all groups before or after L-NAME inhibition. Systemic and renal vasoconstrictor responses to L-NAME were also similar in all genotypes. We conclude that Cx40 contributes to RBF autoregulation by transducing TGF-mediated signals to the afferent arteriole, a function that is independent of nitric oxide (NO). However, Cx40 is not required for the modulation of the renal myogenic response by NO, norepinephrine-induced renal vasoconstriction, and acetylcholine-or NO-induced vasodilation.

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Section: Discussionmentioning

confidence: 99%

Connexin 40 Mediates the Tubuloglomerular Feedback Contribution to Renal Blood Flow Autoregulation

Just

Kurtz

Wit

et al. 2009

Journal of the American Society of Nephrology

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“…Input and output auto power spectra and cross power spectra were then calculated for each segment and averaged. The admittance function was computed as the ratio of cross spectrum to BP power spectrum (30,32,34). The coherence function was also computed from the cross and auto power spectra.…”

Section: Rmrmentioning

confidence: 99%

“…Moreover, AR is not instantaneous (9, 15, 16, 29-33, 45, 47) and impairments in AR allowing an enhanced BP transmission could occur due to either a diminished magnitude of the response or due to a slower rate of response (34). Conventional step AR studies assess only the potential magnitude of the steady-state AR response to BP steps, but not its dynamic aspects (17,29,30,(32)(33)(34). Therefore, it has been suggested that "dynamic" AR studies may provide a more physiological and thus more valid assessment of AR capacity in addition to characterizing the operational characteristics of the myogenic and tubuloglomerular feedback (TGF) mechanisms through frequency domain analysis (1, 11, 12, 14-17, 29, 30, 33, 34, 49).…”

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confidence: 99%

“Step” vs. “dynamic” autoregulation: implications for susceptibility to hypertensive injury

Bidani¹,

Hacıoğlu²,

Abu-Amarah³

et al. 2003

American Journal of Physiology-Renal Physiology

132

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. "Step" vs. "dynamic" autoregulation: implications for susceptibility to hypertensive injury. Am J Physiol Renal Physiol 285: F113-F120, 2003. First published March 11, 2003 10.1152/ajprenal.00012.2003.-Renal autoregulatory (AR) mechanisms provide the primary protection against transmission of systemic pressures, and their impairment is believed to be responsible for the enhanced susceptibility to hypertensive renal damage in renal mass reduction (RMR) models. Assessment of AR capacity by the "step" change methodology under anesthesia was compared with that by "dynamic" methods in separate conscious control Sprague-Dawley rats and after uninephrectomy (UNX) and 3 ⁄4 RMR (RK-NX) (n ϭ 7-10/group). Substantially less AR capacity was seen by the dynamic vs. the step methodology in control rats. Moreover, dynamic AR capacity did not differ among controls, UNX, and RK-NX rats (fractional gain in admittance ϳ0.4-0.5 in all groups at frequencies in the range of 0.0025-0.025 Hz). By contrast, significant impairment of step AR was seen in RK-NX vs. control or UNX rats (AR indexes 0.7 Ϯ 0.1 vs. 0.1 Ϯ 0.02 and 0.2 Ϯ 0.04, respectively, P Ͻ 0.01). We propose that the step and dynamic methods evaluate the renal AR responses to different components of blood pressure (BP) power with the step AR assessing the ability to buffer large changes in average BP (DC power), whereas the present "dynamic" methods assess the AR ability to buffer slow BP fluctuations (Ͻ0.25 Hz) superimposed on the average BP (AC power), a substantially smaller component of total BP power. We further suggest that step but not dynamic AR methods as presently performed provide a valid index of the underlying susceptibility to hypertensive glomerular damage after RMR. renal hemodynamics; hypertension; nephrosclerosis; myogenic response; tubuloglomerular feedback CHRONIC RENAL DISEASE regardless of etiology tends to follow a progressively downhill course (8, 36). Experimental animal models of renal mass reduction (RMR) exhibit a similar course of progressive glomerulosclerosis (GS) and nephron loss. On the basis of investigations in such models, it has been proposed that the loss of a critical degree of functional renal mass results in the initiation and perpetuation of pathogenetic mechanisms that are intrinsic to the reduced functional renal mass state (8,19,35,36,39,40). Several lines of evidence have indicated that an exaggerated transmission of systemic blood pressure (BP) to the glomerular capillaries is one such major pathogenetic mechanism (3-7, 23-26, 39-41). The pathophysiological basis for this enhanced glomerular BP transmission after RMR has been postulated to be due to an impairment of the renal autoregulatory (AR) mechanisms that normally provide the primary protection against BP increases, episodic or sustained, from being transmitted to the renal microvasculature (3,5,7,(23)(24)(25)(26)(27)(37)(38)(39)(40)(41).To date, such renal AR impairment in RMR models has only been demonstrated using the conventional "step" AR methodology in which grade...

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“…The origin of this phenomenon is unclear, but very low frequency oscillations in RBF have been noted in conscious dogs and attributed to fluctuations in ambient levels of vasoactive agents (28). Very low frequency oscillations in RBF have also been induced by blood pressure forcing (11), and may be related to the slow component of renal autoregulation suggested by Just and coworkers (18,19). Furthermore, because of the known interactions between the TGF and myogenic mechanisms, the fact that both autoregulatory systems exhibited some degree of nonstationarity is to be expected.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, both the myogenic mechanism (25) and TGF (31) are extensively modulated by ANG II, the generation of which is at least partly TGF dependent. Furthermore, there are nonlinear interactions between these two systems that produce spectral peaks (7,21,24) and changes in overall system behavior (19,20). In addition, the state of the TGF system appears to modulate the resonant frequency of the myogenic mechanism (26,27).…”

Section: Discussionmentioning

confidence: 99%

Analysis of nonstationarity in renal autoregulation mechanisms using time-varying transfer and coherence functions

Chon¹,

Zhong²,

Moore³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Chon KH, Zhong Y, Moore LC, Holstein-Rathlou NH, Cupples WA. Analysis of nonstationarity in renal autoregulation mechanisms using time-varying transfer and coherence functions. Am J Physiol Regul Integr Comp Physiol 295: R821-R828, 2008. First published May 21, 2008 doi:10.1152/ajpregu.00582.2007.-The extent to which renal blood flow dynamics vary in time and whether such variation contributes substantively to dynamic complexity have emerged as important questions. Data from Sprague-Dawley rats (SDR) and spontaneously hypertensive rats (SHR) were analyzed by time-varying transfer functions (TVTF) and time-varying coherence functions (TVCF). Both TVTF and TVCF allow quantification of nonstationarity in the frequency ranges associated with the autoregulatory mechanisms. TVTF analysis shows that autoregulatory gain in SDR and SHR varies in time and that SHR exhibit significantly more nonstationarity than SDR. TVTF gain in the frequency range associated with the myogenic mechanism was significantly higher in SDR than in SHR, but no statistical difference was found with tubuloglomerular (TGF) gain. Furthermore, TVCF analysis revealed that the coherence in both strains is significantly nonstationary and that low-frequency coherence was negatively correlated with autoregulatory gain. TVCF in the frequency range from 0.1 to 0.3 Hz was significantly higher in SDR (7 out of 7, Ͼ0.5) than in SHR (5 out of 6, Ͻ0.5), and consistent for all time points. For TGF frequency range (0.03-0.05 Hz), coherence exhibited substantial nonstationarity in both strains. Five of six SHR had mean coherence (Ͻ0.5), while four of seven SDR exhibited coherence (Ͻ0.5). Together, these results demonstrate substantial nonstationarity in autoregulatory dynamics in both SHR and SDR. Furthermore, they indicate that the nonstationarity accounts for most of the dynamic complexity in SDR, but that it accounts for only a part of the dynamic complexity in SHR.hemodynamics; myogenic; tubuloglomerular feedback; hypertension AUTOREGULATION OF RENAL BLOOD flow is mediated by the myogenic responses of the preglomerular vasculature (MYO) and the TGF feedback system. These two mechanisms exhibit characteristic resonant frequencies (MYO, 0.1-0.3 Hz; TGF, 0.02-0.05 Hz in rats). The marked difference in characteristic frequencies (and, hence, in time constants) between the TGF and MYO mechanisms permit separation and quantification of contributions of the two mechanisms by transfer function (1, 4, 29) and coherence analyses (2,12).A transfer function is the input-output relationship between an independent variable (blood pressure) and a dependent variable [renal blood flow (RBF)]. Its output is given in terms of gain, which reports fluctuation of the output with respect to the input and phase that contains the temporal relationship between the two signals. Thus, normalized gain Ͻ0 dB indicates that RBF is stabilized with respect to blood pressure and hence that autoregulation is effective. The coherence function assesses the degree to which the data are related ...

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

Cited by 45 publications

References 50 publications

Connexin 40 Mediates the Tubuloglomerular Feedback Contribution to Renal Blood Flow Autoregulation

Connexin 40 Mediates the Tubuloglomerular Feedback Contribution to Renal Blood Flow Autoregulation

“Step” vs. “dynamic” autoregulation: implications for susceptibility to hypertensive injury

Analysis of nonstationarity in renal autoregulation mechanisms using time-varying transfer and coherence functions

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