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

Abstract

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.

Figure 1. Step response of renal vascular resistance (RVR) after sudden release from a reduction of renal artery pressure

Averaged time course of RVR before and after reduction of renal artery pressure to 50 mmHg for 60 s. The period of pressure reduction is not shown. Time = 0 s corresponds to the time of release from the pressure reduction. Mean (continuous trace) ± s.e.m. (dotted traces) from pooled data of all 16 control experiments.

Figure 2. Normalized step response of RVR in response to normal, reduced and elevated levels of angiotensin II (ANGII)

Averaged time course of RVR after release from a reduction of renal artery pressure to 50 mmHg for 60 s. Time = 0 s corresponds to the time of release from the pressure reduction. Values are normalized to the total RVR response between the baseline level before the pressure reduction (100 %) and the minimum level immediately after release (0 %). Mean (continuous traces) ± s.e.m. (dotted traces). A, pooled control response from all 16 control experiments. B, response during control conditions (thin line) and after inhibition of endogenous ANGII formation by ramipril (thick line) in 8 dogs. C, response during control conditions (thin line) and during elevation of plasma ANGII above the resting level by chronic ANGII infusion (5 ng kg⁻¹ min⁻¹) after ramipril treatment (thick line) in 8 dogs.

Figure 3. Transfer function between renal blood flow (RBF) and arterial pressure (RAP) in response to normal, reduced and elevated levels of ANGII

Averaged spectra of the gain of the transfer function between the spontaneous fluctuations of RBF and RAP in resting conscious dogs over 4 h. Gain values are expressed in decibels. Mean (continuous lines) ± s.e.m. (dotted lines). A, pooled baseline spectrum of all 13 control experiments. B, spectra during control conditions (thin line) and after inhibition of endogenous ANGII formation by ramipril (thick line) in 6 dogs. C, spectra during control conditions (thin line) and after elevation of plasma ANGII levels above the resting level by chronic ANGII infusion (5 ng kg⁻¹ min⁻¹) after ramipril treatment (thick line) in 7 dogs.