Autoregulation of renal blood flow in the conscious dog and the contribution of the tubuloglomerular feedback

Abstract

The aim of this study was to investigate the autoregulation of renal blood flow under physiological conditions, when challenged by the normal pressure fluctuations, and the contribution of the tubuloglomerular feedback (TGF). The transfer function between 0.0018 and 0.5 Hz was calculated from the spontaneous fluctuations in renal arterial blood pressure (RABP) and renal blood flow (RBF) in conscious resting dogs. The response of RBF to stepwise artificially induced reductions in RABP was also studied (stepwise autoregulation). Under control conditions (n= 12 dogs), the gain of the transfer function started to decrease, indicating improving autoregulation, below 0.06‐0.15 Hz (t= 7‐17 s). At 0.027 Hz a prominent peak of high gain was found. Below 0.01 Hz (t> 100 s), the gain reached a minimum (maximal autoregulation) of ‐6.3 ± 0.6 dB. The stepwise autoregulation (n= 4) was much stronger (‐19.5 dB). The time delay of the transfer function was remarkably constant from 0.03 to 0.08 Hz (high frequency (HF) range) at 1.7 s and from 0.0034 to 0.01 Hz (low frequency (LF) range) at 14.3 s, respectively. Nifedipine, infused into the renal artery, abolished the stepwise autoregulation (‐2.0 ± 1.1 dB, n= 3). The gain of the transfer function (n= 4) remained high down to 0.0034 Hz; in the LF range it was higher than in the control (0.3 ± 1.0 dB, P< 0.05). The time delay in the HF range was reduced to 0.5 s (P < 0.05). After ganglionic blockade (n= 7) no major changes in the transfer function were observed. Under furosemide (frusemide) (40 mg + 10 mg h−1 or 300 mg + 300 mg h−1 i.v.) the stepwise autoregulation was impaired to ‐7.8 ± 0.3 or ‐6.7 ± 1.9 dB, respectively (n= 4). In the transfer function (n= 7 or n= 4) the peak at 0.027 Hz was abolished. The delay in the LF range was reduced to ‐1.1 or ‐1.6 s, respectively. The transfer gain in the LF range (‐5.5 ± 1.2 or ‐3.8 ± 0.8 dB, respectively) did not differ from the control but was smaller than that under nifedipine (P < 0.05). It is concluded that the ample capacity for regulation of RBF is only partially employed under physiological conditions. The abolition by nifedipine and the negligible effect of ganglionic blockade show that above 0.0034 Hz it is almost exclusively due to autoregulation by the kidney itself. TGF contributes to the maximum autoregulatory capacity, but it is not required for the level of autoregulation expended under physiological conditions. Around 0.027 Hz, TGF even reduces the degree of autoregulation.

Quantification of renal perfusion abnormalities using an intravascular contrast agent (part 2): Results in animals and humans with renal artery stenosis

“…Different degrees of renal artery stenosis were created by graded inflation of an implanted cuff placed around the artery downstream of the flow probe (19). The cuff was filled with saline from a small reservoir (5 ml) and controlled by pressurized air.…”

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

“…After a resting period of 10 min, five pressure reductions were conducted (n ϭ 6) under control conditions at 10,20,30,35, and 40 min after the start of the experiment, i.e., with intercalated recovery periods of 9 min between the first three and 4 min between the last three pressure reductions. Nine minutes after the last pressure reduction, furosemide was injected (20 mg/kg iv; i.e., Ͼ600 mg).…”

“…Although in the kidney the myogenic response seems to reach its maximum effect within a few seconds after activation (10,12,21,30,53), TGF comprises a delay of 10-20 s (7, 13) and requires 1-2 min to achieve its full response (6,7,13). Therefore, it is possible to dissociate both mechanisms by their distinct temporal characteristics.…”

“…Therefore, the contribution of the myogenic response has so far been deduced only by means of exclusion from the degree of autoregulation, which is left after blockade of the TGF by direct interruption (32,44), clamping (42) of tubular flow, ureter occlusion (14,41), or furosemide (2,30,37). Due to these experimental constraints, it cannot be excluded that the remnant autoregulation after blockade of the TGF comprises further regulatory mechanisms in addition to the myogenic response.…”

“…This has been done successfully already by studying the transfer function (2,12,14,21,30) and by analyzing the autoregulatory response to a step increase in perfusion pressure (24,40,43,45,51,53). Transfer function studies have shown that although active under physiological conditions (2,12,14,21,30), the TGF is not required to explain the limited autoregulatory strength, which is observed under these conditions (2,14,30). However, the transfer function does not allow for assessment of the actual contribution of the TGF under resting conditions.…”