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Muscle‐derived vascular endothelial growth factor regulates microvascular remodelling in response to increased shear stress in mice
Author(s) -
Uchida C.,
Nwadozi E.,
Hasanee A.,
Olenich S.,
Olfert I. M.,
Haas T. L.
Publication year - 2015
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12463
Subject(s) - endocrinology , medicine , skeletal muscle , myocyte , prazosin , blood vessel , vascular smooth muscle , vascular endothelial growth factor , vasodilation , biology , chemistry , receptor , vegf receptors , smooth muscle , antagonist
Abstract Aim The source of vascular endothelial growth factor‐A ( VEGF ‐A) may influence vascular function. Exercise‐induced vascular growth has been attributed to elevated metabolic demand and to increased blood flow, involving the production of VEGF ‐A by skeletal muscle and by endothelial cells respectively. We hypothesized that muscle‐derived VEGF ‐A is not required for vascular adaptations to blood flow in skeletal muscle, as this remodelling stimulus originates within the capillary. Methods Myocyte‐specific VEGF ‐A ( mVEGF ‐/‐ ) deleted mice were treated for 7–21 days with the vasodilator prazosin to produce a sustained increase in skeletal muscle blood flow. Results Capillary number increased in the extensor digitorum longus ( EDL ) muscle in response to prazosin in wild type but not mVEGF ‐/‐ mice. Prazosin increased the number of smooth muscle actin‐positive blood vessels in the EDL of wild‐type but not mVEGF ‐/‐ mice. The average size of smooth muscle actin‐positive blood vessels also was smaller in knockout mice after prazosin treatment. In response to prazosin treatment, VEGF ‐A mRNA was elevated within the EDL of wild‐type but not mVEGF ‐/‐ mice. Ex vivo incubation of wild‐type EDL with a nitric oxide donor increased VEGF ‐A mRNA . Likewise, we demonstrated that nitric oxide donor treatment of cultured myoblasts stimulated an increase in VEGF ‐A mRNA and protein. Conclusion These results suggest a link through which flow‐mediated endothelial‐derived signals may promote myocyte production of VEGF ‐A. In turn, myocyte‐derived VEGF ‐A is required for appropriate flow‐mediated microvascular remodelling. This highlights the importance of the local environment and paracrine interactions in the regulation of tissue perfusion.