LOW-MOLECULAR-MASS ENDOTHELIAL CELL-STIMULATING ANGIOGENIC FACTOR IN RELATION TO CAPILLARY GROWTH INDUCED IN RAT SKELETAL-MUSCLE BY LOW-FREQUENCY ELECTRICAL-STIMULATION

The involvement of endothelial cell-stimulating angiogenic factor (ESA F) in capillary growth was studied in adult rat skeletal muscles (tibi alis anterior, TA, and extensor digitorum longus, EDL) in which capill ary growth was induced by chronic unilateral electrical stimulation (1 0 Hz, 8 h/day for 7 days), and in sham-operated and unoperated control muscles. ESAF was assayed by its ability to activate latent collagena se in units per hour per milligram protein. Anatomical capillary densi ty (CD, number of capillaries per mm(2)) and capillary per fibre ratio (C/F) were estimated in frozen sections from the same muscles after s taining for endothelial alkaline phosphatase. In control muscles, ESAF levels were inversely related to capillary supply, being highest (1.8 2 +/- 0.25 units) in the glycolytic cortex of TA (CD 273 +/- 18/mm(2), C/F 1.26 +/- 0.07), lowest (1.04 +/- 0.02 units) in its oxidative hig hly capillarized core (CD 862 +/- 60/mm(2), C/F 2.05 +/- 0.04), and in termediate in EDL (ESAF 1.59 +/- 0.37 units, CD 527 +/- 26/mm(2), C/F 1.44 +/- 0.06). Neither capillary supply nor ESAF levels were affected by sham operation. However, chronic electrical stimulation increased capillary supply significantly in EDL (CD 61% greater than in controls , C/F 45% greater) and ESAF levels were elevated 3-fold to 4.77 +/- 0. 74 units. In TA muscles, stimulation increased capillary supply specif ically in the glycolytic cortex (C/F 2.51 +/- 0.09, p < 0.0001 vs. con trol) and ESAF levels were increased significantly in this region to 3 .19 +/- 0.55 units (p < 0.05, vs. control). C/F ratio and ESAF in the oxidative core of TA (2.31 +/- 0.05 and 1.48 +/- 0.23 units, respectiv ely) were not significantly different from control values. Thus, chron ic electrical stimulation, which is known to increase both shear stres s and wall tension in capillaries and induce angiogenesis, also increa sed ESAF activity.