Renal segmental microvascular responses to ANG II in AT1A receptor null mice

Abstract

The relative contributions of AT1A and AT1B receptors to afferent arteriolar autoregulatory capability and afferent and efferent arteriolar responses to ANG II are not known. Experiments were conducted in kidneys from wild-type (WT) and AT1A−/− mice utilizing the in vitro blood-perfused juxtamedullary nephron technique. Direct measurements of afferent (AAD) and efferent arteriolar diameters (EAD) were assessed at a renal arterial pressure of 100 mmHg. AAD averaged 14.8 ± 0.8 μm for WT and 14.9 ± 0.8 μm for AT1A−/− mice. AAD significantly decreased by 7 ± 1, 16 ± 1, and 26 ± 2% for WT mice and by 11 ± 1, 20 ± 2, and 30 ± 3% for AT1A−/− mice (120, 140, 160 mmHg). AAD autoregulatory capability was not affected by the absence of AT1A receptors. AAD responses to 10 nM ANG II were significantly blunted for AT1A−/− mice compared with WT (−22 ± 2 vs. −37 ± 5%). ANG II (0.1–10 nM) failed to elicit any change in EAD for AT1A−/− mice. AAD and EAD reductions in ANG II were blocked by 1 μM candesartan. We conclude that afferent arteriole vasoconstrictor responses to ANG II are mediated by AT1A and AT1B receptors, whereas efferent arteriolar vasoconstrictor responses to ANG II are mediated by only AT1A receptors in the mouse kidney.