Angiotensin II Enhances Tubuloglomerular Feedback Via Activation of Luminal At1 Receptors on the Macula Densa
Angiotensin II (Ang II) enhances tubuloglomerular feedback (TGF) through its actions on the afferent arteriole (Af-Art). Recent studies revealed AT1-receptors on macula densa cells, raising the possibility that Ang II could enhance 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. Rabbit Af-Arts and the attached macula densa were simultaneously microperfused in vitro. Af-Art diameter was measured while the macula densa was perfused with low NaCl (Na+: 5 mM; Cl-: 3 mM) and then with high NaCl (Na+: 79 mM; Cl-: 77 mM). In the absence of Ang II, Af-Art diameter decreased by 2.4 ± 0.5 μm (from 17.3 ± 1.0 to 14.9 ± 1.2 μm) when the NaCl concentration at the macula densa was increased. After adding Ang II (0.1 nM) to the lumen of the macula densa, the diameter decreased by 3.8 ± 0.7 μm (p<0.02 compared to control; n=8). To make sure that this effect was not due to Ang II entering the bath and affecting the Af-Art, we repeated this experiment with losartan in the bath. In the absence of Ang II with losartan (1 μM) in the bath, diameter decreased by 2.7 ± 0.5 μm (from 19.3 ± 1.2 to 16.6 ± 0.8 μm). After Ang II was added to the macula densa perfusate, the TGF response was 4.0 ± 0.7 μm (p<0.01; n=8). This concentration of losartan completely blocked the direct effects of Ang II on the Af-Art. To test whether Ang II enhances TGF via activation of AT1 receptors on the luminal membrane of the macula densa, we compared the TGF response in the presence and absence of Ang II plus losartan in the macula densa perfusate. With losartan in the macula densa perfusate, Af-Art diameter decreased by 2.5 ± 0.5 μm (from 16.7 ± 1.8 to 14.2 ± 2.1 μm). When Ang II was added to the macula densa perfusate with losartan, the TGF response was 2.7 ± 1.1 μm (n.s.). We concluded that Ang II enhances TGF via activation of AT1 receptors on the luminal membrane of the macula densa.