Uwe Wittmann

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

1 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). 2 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). 3 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. 4 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). 5 After ganglionic blockade (n= 7) no major changes in the transfer function were observed. 6 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). 7 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.

The SCGM1 System: subcutaneous continuous glucose monitoring based on microdialysis technique.

The SCGM1 System is designed to allow continuous glucose monitoring in the subcutaneous interstitial fluid for up to 120 h. The system is based on the microdialysis technique and is composed of three components: (1) a disposable Cassette, which contains the microdialysis catheter (with the necessary tubes), an electrochemical flow-through sensor for glucose measurement, and the fluid reservoirs for both the microdialysis perfusate and a reagent solution containing glucose oxidase; (2) the Sensor Unit, which houses the Cassette and is worn by the patient using a belt pack; and (3) the Data Manager, with an integrated blood glucose meter for the calibration of the glucose signal. The Data Manager also has the option of displaying the continuous glucose signal. The Sensor Unit and Data Manager exchange glucose data and calibration data by radio transmission. In vitro precision was assessed by measurements of two standard glucose solutions (90 mg/dL, 3.4%; 360 mg/dL, 2.4%) over a time course of 4 days. The mean difference (+/- SD) between SCGM1 System devices (n = 11) and 15 glucose standard solutions with different concentrations was 1.4 +/- 3.5 mg/dL. The mean relative difference and the mean absolute relative difference ranged from - 0.6% to 3.7% and from 0.2% to 3.8%, respectively. The inherent physical lag time was 31 +/- 2 min (n = 10). The interference on the glucose signal of ascorbic acid, acetaminophen, and uric acid at the highest physiological concentrations was below 4%. The SCGM1 System showed a reliable and precise performance under in vitro conditions.

Role of angiotensin II in dynamic renal blood flow autoregulation of the conscious dog

The influence of angiotensin II (ANGII) on the dynamic characteristics of renal blood flow (RBF) was studied in conscious dogs by testing the response to a step increase in renal artery pressure (RAP) after a 60 s period of pressure reduction (to 50 mmHg) and by calculating the transfer function between physiological fluctuations in RAP and RBF. During the RAP reduction, renal vascular resistance (RVR) decreased and upon rapid restoration of RAP, RVR returned to baseline with a characteristic time course: within the first 10 s, RVR rose rapidly by 40 % of the initial change (first response, myogenic response). A second rise began after 20–30 s and reached baseline after an overshoot at 40 s (second response, tubuloglomerular feedback (TGF)). Between both responses, RVR rose very slowly (plateau). The transfer function had a low gain below 0.01 Hz (high autoregulatory efficiency) and two corner frequencies at 0.026 Hz (TGF) and at 0.12 Hz (myogenic response). Inhibition of angiotensin converting enzyme (ACE) lowered baseline RVR, but not the minimum RVR at the end of the RAP reduction (autoregulation‐independent RVR). Both the first and second response were reduced, but the normalised level of the plateau (balance between myogenic response, TGF and possible slower mechanisms) and the transfer gain below 0.01 Hz were not affected. Infusion of ANGII after ramipril raised baseline RVR above the control condition. The first and second response and the transfer gain at both corner frequencies were slightly augmented, but the normalised level of the plateau was not affected. It is concluded that alterations of plasma ANGII within a physiological range do not modulate the relative contribution of the myogenic response to the overall short‐term autoregulation of RBF. Consequently, it appears that ANGII augments not only TGF, but also the myogenic response.

Tonic and phasic influences of nitric oxide on renal blood flow autoregulation in conscious dogs

The aim of this study was to investigate the influence of the mean level and phasic modulation of NO on the dynamic autoregulation of renal blood flow (RBF). Transfer functions were calculated from spontaneous fluctuations of RBF and arterial pressure (AP) in conscious resting dogs for 2 h under control conditions, after NO synthase (NOS) inhibition [ N G-nitro-l-arginine methyl ester hydrochloride (l-NAME)] and afterl-NAME followed by a continuous infusion of an NO donor [ S-nitroso- N-acetyl-dl-penicillamine (SNAP)]. After l-NAME ( n = 7) AP was elevated, heart rate (HR) and RBF were reduced. The gain of the transfer function above 0.08 Hz was increased, compatible with enhanced resonance of the myogenic response. A peak of high gain around 0.03 Hz, reflecting oscillations of the tubuloglomerular feedback (TGF), was not affected. The gain below 0.01 Hz, was elevated, but still less than 0 dB, indicating diminished but not abolished autoregulation. Afterl-NAME and SNAP ( n = 5), mean AP and RBF were not changed, but HR was slightly elevated. The gain above 0.08 Hz and the peak of high gain at 0.03 Hz were not affected. The gain below 0.01 Hz was elevated, but smaller than 0 dB. It is concluded that NO may help to prevent resonance of the myogenic response depending on the mean level of NO. The feedback oscillations of the TGF are not affected by NO. NO contributes to the autoregulation below 0.01 Hz due to phasic modulation independent of its mean level.