Differential effect of angiotensin II on blood circulation in the renal medulla and cortex of anaesthetised rats

Abstract

The renal medulla is sensitive to hypoxia, and a depression of medullary circulation, e.g. in response to angiotensin II (Ang II), could endanger the function of this zone. Earlier data on Ang II effects on medullary vasculature were contradictory. The effects of Ang II on total renal blood flow (RBF), and cortical and medullary blood flow (CBF and MBF: by laser-Doppler flux) were studied in anaesthetised rats. Ang II infusion (30 ng kg(-1) min(-1) i.v.) decreased RBF 27 +/- 2 % (mean +/- S.E.M.), whereas MBF increased 12 +/- 2 % (both P < 0.001). Non-selective blockade of Ang II receptors with saralasin (3 microg kg(-1) min(-1) i.v.) increased RBF 12 +/- 2 % and decreased MBF 8 +/- 2 % (P < 0.001). Blockade of AT(1) receptors with losartan (10 mg kg(-1)) increased CBF 10 +/- 2 % (P < 0.002) and did not change MBF. Losartan given during Ang II infusion significantly increased RBF (53 +/- 7 %) and decreased MBF (27 +/- 7 %). Blockade of AT(2) receptors with PD 123319 (50 microg kg(-1) min(-1) i.v.) did not change CBF or MBF. Intramedullary infusion of PD 123319 (10 microg min(-1)) superimposed on intravenous Ang II infusion did not change RBF, but slightly decreased MBF (4 +/- 2 %, P < 0.05). We conclude that in anaesthetised surgically prepared rats, exogenous or endogenous Ang II may not depress medullary circulation. In contrast to the usual vasoconstriction in the cortex, vasodilatation was observed, possibly related to secondary activation of vasodilator paracrine agents rather than to a direct action via AT(2) receptors.

Figure 1. Effect of i.v. Ang II infusion (30 ng kg⁻¹ min⁻¹) on total RBF and renal MBF (LD flux)

The RPP was allowed to increase (A, n = 8) or was maintained constant at 102 ± 1 mmHg (B, n = 39 for RBF and n = 31 for MBF). Data are presented as means ± s.d. as a percentage of the initial control value. C, control; R, post-Ang II recovery. *P < 0.05 or less versus control.

Figure 2. Effect of i.v. captopril administration on renal CBF and MBF (LD fluxes)

Captopril was given i.v. as a bolus, 1 mg kg⁻¹, followed by an infusion of 1 mg kg⁻¹ h⁻¹i.v., at constant RPP (n = 17). Data are presented as means ± s.e.m., as a percentage of the initial control value. *P < 0.0001 versus control.

Figure 3. Sample records of total RBF (A) and MBF (B) responses to i.v. saralasin (3 μg kg⁻¹ min⁻¹) in two experiments

In one experiment, Ang II was continuously infused at 30 ng kg⁻¹ min⁻¹i.v. In the other, Ang II vehicle was given. PU, LD perfusion units.

Figure 4. Biphasic effect of i.v. saralasin (S, 3 μg kg⁻¹ min⁻¹) on total RBF and MBF

A, data recorded with Ang II vehicle (n = 13). B, data recorded with background Ang II infusion, 30 ng kg⁻¹ min⁻¹i.v. (n = 17). The RPP was maintained constant. S-1, S-2, early and final effects of saralasin, respectively. Means ± s.d. for values expressed as a percentage of the pre-saralasin control value (C). *P < 0.05 or less versus pre-saralasin control. †P < 0.002 or less versus the change in the corresponding value measured without background Ang II infusion (A).

Figure 5. Effects of i.v. losartan on renal haemodynamics

A, effects of losartan, 10 mg kg⁻¹i.v. (n = 10), on renal CBF and MBF. B, total RBF and MBF after losartan given in the same dose during Ang II infusion, 30 ng kg⁻¹ min⁻¹i.v. (n = 10). Data are presented as means ± s.d., as a percentage of the pre-losartan control value. *P < 0.05 or less versus pre-losartan control. †P < 0.001 versus the CBF value measured after losartan alone (as shown in A).

Figure 6. The renal MBF responses to PD 123319 (PD)

PD 123319 was given i.v., 50 μg kg⁻¹ min⁻¹ (PD; n = 8), or infused directly into the medullary interstitium, 5–10 μg min⁻¹, during background infusion of Ang II (30 ng kg⁻¹ min⁻¹i.v.) (Ang II + PD; n = 12). The RPP was maintained constant in both groups. Data are presented as means ± s.e.m. as a percentage of the pre-PD control value. *P < 0.05 versus pre-PD control.