Angiotensin II enhances tubuloglomerular feedback via luminal AT1 receptors on the macula densa

Angiotensin II enhances tubuloglomerular feedback via luminal AT1 receptors on the macula densa.BackgroundRecent studies have revealed angiotensin II subtype 1 (AT1) receptors on macula densa cells, raising the possibility that angiotensin II (Ang II) could enhance tubuloglomerular feedback (TGF) by affecting macula densa cell function. We hypothesized that Ang II enhances TGF via activation of AT1 receptors on the luminal membrane of the macula densa.MethodsRabbit afferent arterioles and the attached macula densa were simultaneously microperfused in vitro, keeping pressure in the afferent arteriole at 60mm Hg.ResultsThe afferent arteriole diameter was measured while the macula densa was perfused with low NaCl (Na+, 5 mmol/L; Cl-, 3 mmol/L) and then with high NaCl (Na+, 79 mmol/L; Cl-, 77 mmol/L) to induce a TGF response. When TGF was induced in the absence of Ang II, the afferent arteriole diameter decreased by 2.4 ± 0.5 μm (from 17.3 ± 1.0 to 14.9 ± 1.2 μm). With Ang II (0.1 nmol/L) present in the lumen of the macula densa, the diameter decreased by 3.8 ± 0.7 μm (from 17.3 ± 1.0 to 13.5 ± 1.2 μm, P < 0.05 vs. TGF with no Ang II, N = 8). To test whether Ang II enhances TGF via activation of AT1 receptors on the luminal membrane of the macula densa, Ang II plus losartan (1 μmol/L) was added to the lumen. Losartan itself did not alter TGF. When TGF was induced in the absence of Ang II and losartan, the afferent arteriole diameter decreased by 2.3 ± 0.3 μm (from 15.9 ± 1.0 to 13.6 ± 1.2 μm). When Ang II and losartan were both present in the macula densa perfusate, the diameter decreased by 2.4 ± 0.4 μm (from 15.8 ± 0.9 to 13.4 ± 0.7 μm, P< 0.8 vs. TGF with no Ang II and losartan, N = 7). We then examined whether AT2 receptors on the macula densa influence the effect of luminal Ang II on TGF. When TGF was induced in the absence of Ang II plus PD 0123319-0121B (1 μmol/L), the afferent arteriole diameter decreased by 2.4 ± 0.2 μm (from 17.0 ± 0.9 to 14.6 ± 0.8 μm). When Ang II and PD 0123319-0121B were both present in the macula densa lumen, the diameter decreased by 3.9 ± 0.2 μm (from 16.8 ± 0.9 to 12.9 ± 0.9 μm, P < 0.001 vs. TGF with no Ang II and PD 0123319-0121B, N = 8). PD 0123319-0121B itself had no effect on TGF. To assure that this effect of Ang II was not due to leakage into the bath, losartan was added to the bath. When TGF was induced in the absence of Ang II with losartan in the bath, the afferent arteriole diameter decreased by 2.8 ± 0.5 μm (from 19.3 ± 1.2 to 16.5 ± 0.8 μm). After Ang II was added to the macula densa perfusate and losartan to the bath, the diameter decreased by 4.0 ± 0.7 μm (from 18.9 ± 1.1 to 14.9 ± 0.5 μm, P < 0.01 vs. TGF with no Ang II in the lumen and losartan in the bath, N = 8).ConclusionsThese results demonstrate that Ang II enhances TGF via activation of AT1 receptors on the luminal membrane of the macula densa