Neural programming of mesenteric and renal arteries

摘要: There is evidence for developmental origins of vascular dysfunction yet little understanding maturation smooth muscle (VSM) regional circulations. We measured maturational changes in expression myosin phosphatase (MP) and the broader VSM gene program relation to mesenteric small resistance artery (SRA) function. then tested role sympathetic nervous system (SNS) programming SRAs used genetically engineered mice define MP isoforms functional circulation. Maturation rat as by qPCR immunoblotting begins after second postnatal week not complete until maturity. It characterized induction markers differentiation (smMHC, γ-, α-actin), CPI-17, an inhibitory subunit a key target α-adrenergic vasoconstriction, α1-adrenergic, purinergic X1, neuropeptide Y1 receptors signaling. Functional correlates include increases α-adrenergic-mediated force calcium sensitization production (MP inhibition) first-order arteries ex vivo. The regulatory Mypt1 E24+/LZ- isoform specifically upregulated during maturation. Conditional deletion mouse E24 demonstrates that splicing causes reduction sensitivity cGMP-mediated vasorelaxation activation). Neonatal chemical sympathectomy (6-hydroxydopamine) suppresses with minimal effect on conduit artery. Mechanical denervation mature renal reversion immature program. conclude SNS captures control circulation SRA muscle.