Cunha, Shane R.

Ankyrin B (AnkB) plays an important role in normal cardiac and neuronal function by linking membrane proteins to the cytoskeleton. Little is known, however, about the role of AnkB in the vasculature. Thus, we studied vasomotor function in aortas from wild‐type mice (AnkB +/+ ) and AnkB‐deficient littermates (AnkB +/− ). Maximum relaxation (M R ) to acetylcholine (Ach) was significantly reduced in AnkB +/− mice relative to AnkB +/+ mice (68 ± 5% vs 80 ± 1%), while responses to sodium nitroprusside were unaffected. While constrictor responses to PGF 2 α (1.5 ± 0.1g vs 1.4 ± 0.1g) were unchanged in AnkB +/− mice, constriction to phenylephrine was reduced by >35% in AnkB +/− mice compared to their AnkB +/+ littermates (p < 0.05). Incubation of AnkB +/+ vessels with the IP 3 ‐receptor inhibitor 2‐APB impaired M R to Ach in both AnkB +/+ and AnkB +/− mice (28 ± 6% and 29 ± 3%, respectively). Vasoconstrictor responses to phenylephrine were also dramatically attenuated by 2‐APB in AnkB +/+ mice (0.43 ± 0.05g vs 0.18 ± 0.02g) but not in AnkB +/− mice (0.28 ± 0.05g vs 0.27 ± 0.05g). These data suggest that Ankyrin B plays a significant role in determining both endothelial and vascular smooth muscle function, in part through the modulation of the IP 3 receptor. Future studies examining the molecular mechanisms whereby Ankyrin B affects vasomotor function may lend critical insights into vasomotor dysfunction in health and disease.