Vascular Endothelial Growth Factor, Capillarization, and Function of the Rat Plantaris Muscle at the Onset of Hypertrophy.

Abstract

Skeletal muscle has a great ability to respond to altered functional demands. This response includes, among other adaptations, changes in muscle size, fiber-type composition, and capillary supply, resulting in altered contractile properties and fatigue resistance [1]. The response to the increased functional demand imposed on a muscle by the elimination of agonist muscles involves compensatory hypertrophy. This hypertrophy is accompanied by an increase in the number of type I fibers and capillary proliferation [2][3][4][5][6][7]. Concomitantly, the force generating capacity and fatigue resistance of the hypertrophied muscle increases [3,8].The absence of significant hypertrophy during at least the first week after the functional elimination of synergists [4,9] suggests that the muscle needs time to recover from the early damage [10] before the onset of real growth. Furthermore, the presence of transi- Japanese Journal of Physiology, 53, 181-191, 2003 Key words: capillary, fatigue, specific tension, myosin heavy chain, muscle.Abstract: Capillary proliferation occurs during compensatory hypertrophy. We investigated whether the expression of vascular endothelial growth factor (VEGF) is elevated at the onset of hypertrophy when capillary proliferation is minimal, and whether muscle damage as assessed by muscle force deficits, may occur at the onset of hypertrophy. To investigate this, we induced in 9-month-old rats, under isoflurane anesthesia, hypertrophy of the left plantaris muscle by denervation of the gastrocnemius and soleus muscles. Capillarization was investigated in both the deep (oxidative) and the superficial (glycolytic) regions of the plantaris muscle. After 2 weeks, muscle mass had increased by 16% (pϽ0.01), which was not accompanied by increases in fiber size. The maximal tetanic force (P 0 ) and specific ten-) and twitch characteristics were unaltered, and fatigue resistance of the overloaded muscle was improved (pϽ0.05). However, the myosin heavy chain composition was unaltered. Capillary proliferation was not yet evident, but VEGF mRNA and protein levels were elevated 1.5-and 8-fold, respectively (pϽ0.05). We concluded that the normal specific tension and the elevated VEGF expression after 2 weeks of overload indicate (1) an absence of or minimal muscle damage at this early time point, and (2) that elevated VEGF expression precedes and is involved in capillary proliferation that occurs during the later stages of compensatory hypertrophy.

Maintenance of Heterogeneity of Capillary Spacing is Essential for Adequate Oxygenation in the Soleus Muscle of the Growing Rat

“…Another factor that may induce angiogenesis during growth is the slow but gradual elongation of the muscle during normal growth, causing a chronic mechanical stretch on the muscle and the vessels therein ( 34 ), via induction of HIF and the endothelial mitogen vascular endothelial growth factor (VEGF). Similar to what we report here for normal growth, angiogenesis during compensatory hypertrophy resulted in increased C:F but reduced CD ( 10 ), and was preceded by elevated levels of VEGF ( 6 ).…”

Detraining losses of skeletal muscle capillarization are associated with vascular endothelial growth factor protein expression in rats

“…It is interesting to note, however, that a number of recent studies have observed regional differences in plantaris muscle capillarity (i.e. deep oxidative and superficial glycolytic regions; Degens et al 2003; Zoll et al 2003; Wust et al 2009 a , b ). These studies revealed that the deep oxidative regions have higher capillary density than the superficial glycolytic regions.…”

Nandrolone decanoate modulates cell cycle regulation in functionally overloaded rat soleus muscle

“…The mean soleus fiber CSA was not changed by 3 days of overload or nandrolone decanoate pretreatment. However, mean CSA is not an accurate description of the remodeling events occurring in overloaded skeletal muscle (20). An increased incidence of very small-diameter myofibers in skeletal muscle is an established indicator of regeneration from injury (15,30,55,56).…”