Efferent arterioles exclusively express the subtype 1A angiotensin receptor: functional insights from genetic mouse models

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Abstract
Angiotensin (ANG) type 1A (AT1A) receptor-null (AT1A−/−) mice exhibit reduced afferent arteriolar (AA) constrictor responses to ANG II compared with wild-type (WT) mice, whereas efferent arteriolar (EA) responses are absent (Harrison-Bernard LM, Cook AK, Oliverio MI, and Coffman TM. Am J Physiol Renal Physiol 284: F538–F545, 2003). In the present study, the renal arteriolar constrictor responses to norepinephrine (NE) and/or ANG II were determined in blood-perfused juxtamedullary nephrons from kidneys of AT1A−/−, AT1B receptor-null (AT1B−/−), and WT mice. Baseline AA diameter in AT1A−/− mice was not different from that in WT mice (13.1 ± 0.9 and 12.6 ± 0.9 μm, n = 7 and 8, respectively); however, EA diameters were significantly larger (17.3 ± 1.4 vs. 11.7 ± 0.4 μm, n = 10 and 8) in AT1A−/− than in WT mice. Constriction of AA (−40 ± 8 and −51 ± 6% at 1 μM NE) and EA (−29 ± 6 and −38 ± 3% at 1 μM NE) in response to 0.1–1 μM NE was similar in AT1A−/− and WT mice. Baseline diameters of AA (13.5 ± 0.7 and 14.2 ± 0.9 μm, n = 9 and 10) and EA (15.4 ± 1.0 and 15.0 ± 0.7 μm, n = 11 and 9) and ANG II (0.1–10 nM) constrictor responses of AA (−25 ± 4 and −31 ± 5% at 10 nM) and EA (−32 ± 6 and −35 ± 7% at 10 nM) were similar in AT1B−/− and WT mice, respectively. ANG II-induced constrictions were eliminated by AT1 receptor blockade with 4 μM candesartan. Taken together, our data demonstrate that AA and EA responses to NE are unaltered in the absence of AT1A receptors, and ANG II responses remain intact in the absence of AT1B receptors. Therefore, we conclude that AT1A and AT1B receptors are functionally expressed on the AA, whereas the EA exclusively expresses the AT1A receptor.