| First Author | Reho JJ | Year | 2014 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 307 |
| Issue | 4 | Pages | H563-73 |
| PubMed ID | 24929853 | Mgi Jnum | J:230106 |
| Mgi Id | MGI:5755492 | Doi | 10.1152/ajpheart.00250.2014 |
| Citation | Reho JJ, et al. (2014) Neural programming of mesenteric and renal arteries. Am J Physiol Heart Circ Physiol 307(4):H563-73 |
| abstractText | There is evidence for developmental origins of vascular dysfunction yet little understanding of maturation of vascular smooth muscle (VSM) of regional circulations. We measured maturational changes in expression of myosin phosphatase (MP) and the broader VSM gene program in relation to mesenteric small resistance artery (SRA) function. We then tested the role of the sympathetic nervous system (SNS) in programming of SRAs and used genetically engineered mice to define the role of MP isoforms in the functional maturation of the mesenteric circulation. Maturation of rat mesenteric SRAs as measured by qPCR and immunoblotting begins after the second postnatal week and is not complete until maturity. It is characterized by induction of markers of VSM differentiation (smMHC, gamma-, alpha-actin), CPI-17, an inhibitory subunit of MP and a key target of alpha-adrenergic vasoconstriction, alpha1-adrenergic, purinergic X1, and neuropeptide Y1 receptors of sympathetic signaling. Functional correlates include maturational increases in alpha-adrenergic-mediated force and calcium sensitization of force production (MP inhibition) measured in first-order mesenteric arteries ex vivo. The MP regulatory subunit Mypt1 E24+/LZ- isoform is specifically upregulated in SRAs during maturation. Conditional deletion of mouse Mypt1 E24 demonstrates that splicing of E24 causes the maturational reduction in sensitivity to cGMP-mediated vasorelaxation (MP activation). Neonatal chemical sympathectomy (6-hydroxydopamine) suppresses maturation of SRAs with minimal effect on a conduit artery. Mechanical denervation of the mature rat renal artery causes a reversion to the immature gene program. We conclude that the SNS captures control of the mesenteric circulation by programming maturation of the SRA smooth muscle. |
