AT1 receptors mediate angiotensin II–induced release of nitric oxide in afferent arterioles

AT1 receptors mediate angiotensin II–induced release of nitric oxide in afferent arterioles. Recent studies have indicated that angiotensin II (Ang II) possibly activates the nitric oxide (NO) system. We investigated the role of AT receptor subtypes (AT-R) in mediating the Ang II–induced NO release in afferent arterioles (Af) of mice. Isolated Af of mice were perfused, and the isotonic contraction measured. Further, NO release was determined using DAF-FM, a fluorescence indicator for NO. Moreover, we qualitatively assessed the expression of AT-R at the mRNA level using reverse transcription-polymerase chain reaction (RT-PCR). Ang II reduced luminal diameters dose dependently (67.3 ± 6.3% at 10−6 mol/L). Inhibition of AT2-R with PD123.319 did not change the Ang II contractile response. AT1-R blockade with ZD7155 inhibited contraction. Stimulation of AT2-R during AT1-R inhibition with ZD7155, and preconstriction with norepinephrine (NE) had no influence on the diameter. Drug application via the perfusion pipette changed flow and pressure, and enhanced NO fluorescence by ΔF = 4.0 ± 0.4% (N = 14, background). Luminal application of Ang II (10−7 mol/L) increased the NO fluorescence by ΔF = 9.9 ± 1.2% (N = 8). AT1-R blockade blunted the increase to background levels (ΔF to 4.0 ± 0.3%, N = 6, P < 0.05), but AT2-R blockade did not (8.1 ± 0.9%, N = 9). L-NAME nearly abolished the Ang II effect on the NO fluorescence (ΔF = 1.6 ± 0.5% (N = 8). NE did not increase NO release beyond the background levels. RT-PCR showed expression of both AT1-R and AT2-R. The results indicate an Ang II–induced NO release in Af of mice, which is mediated by AT1-R. Thus, Ang II balances its own constrictor action in Af. This control mechanism is very important in view of high renin and angiotensin II concentration in the juxtaglomerular apparatus.