Neural programming of mesenteric and renal arteries. Am J Physiol Heart Circ Physiol 2014 Aug 15;307(4):H563-73
Date
06/16/2014Pubmed ID
24929853Pubmed Central ID
PMC4137124DOI
10.1152/ajpheart.00250.2014Scopus ID
2-s2.0-84906084563 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
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, γ-, α-actin), CPI-17, an inhibitory subunit of MP and a key target of α-adrenergic vasoconstriction, α1-adrenergic, purinergic X1, and neuropeptide Y1 receptors of sympathetic signaling. Functional correlates include maturational increases in α-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.
Author List
Reho JJ, Zheng X, Benjamin JE, Fisher SAAuthor
John J. Reho Research Scientist II in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ActinsAnimals
Cell Differentiation
Cyclic GMP
Gene Expression Regulation, Developmental
Male
Mesenteric Arteries
Mice
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle
Myosin-Light-Chain Kinase
Myosin-Light-Chain Phosphatase
Rats
Rats, Sprague-Dawley
Renal Artery
Sympathetic Nervous System
Vasoconstriction
Vasodilator Agents
