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IP₃ receptors regulate vascular smooth muscle contractility and hypertension.

ABSTRACT: Inositol 1, 4, 5-trisphosphate receptor-mediated (IP₃R-mediated) calcium (Ca²⁺) release has been proposed to play an important role in regulating vascular smooth muscle cell (VSMC) contraction for decades. However, whether and how IP₃R regulates blood pressure in vivo remains unclear. To address these questions, we have generated a smooth muscle-specific IP₃R triple-knockout (smTKO) mouse model using a tamoxifen-inducible system. In this study, the role of IP₃R-mediated Ca²⁺ release in adult VSMCs on aortic vascular contractility and blood pressure was assessed following tamoxifen induction. We demonstrated that deletion of IP₃Rs significantly reduced aortic contractile responses to vasoconstrictors, including phenylephrine, U46619, serotonin, and endothelin 1. Deletion of IP₃Rs also dramatically reduced the phosphorylation of MLC20 and MYPT1 induced by U46619. Furthermore, although the basal blood pressure of smTKO mice remained similar to that of wild-type controls, the increase in systolic blood pressure upon chronic infusion of angiotensin II was significantly attenuated in smTKO mice. Taken together, our results demonstrate an important role for IP₃R-mediated Ca²⁺ release in VSMCs in regulating vascular contractility and hypertension.

SUBMITTER: Lin Q

PROVIDER: S-EPMC5070959 | biostudies-literature |

REPOSITORIES: biostudies-literature

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