Barry M. Prior

Exercise-induced vascular remodeling.

PRIOR, B.M, P.G. LLOYD, H.T. YANG, and R.L. TERJUNG. Exercise-induced vascular remodeling. Exerc. Sport Sci. Rev. Vol. 31, No. 1, pp. 26-33, 2003. Exercise produces a powerful angiogenic stimulus within the active muscle that leads to a functionally important increase in capillarity. Further, exercise can increase flow capacity by enlarging the caliber of arterial supply vessels. These adaptations are achieved by the processes of angiogenesis and arteriogenesis, respectively.

Arteriogenesis: Role of Nitric Oxide

Arteriogenesis is an important process for adapting the pre-existing circuit of vessels into functional collateral conduits for delivery of oxygen enriched blood to tissue distal to occlusion of a large, peripheral conduit artery. Recent evidence has shown that arteriogenesis is regulated by nitric oxide (NO), angiogenic factors and shear stress. NO significantly impacts vasomotor tone to enhance conductance of the newly recruited collateral arteries, and this effect is augmented by exercise training prior to arterial occlusion. NO-mediated increases in vascular conductance allows for greater collateral dependent blood flow to the tissue distal to occlusion. NO production is also critical to the efficacy of therapeutic arteriogenesis achieved by delivery of exogenous angiogenic growth factors (VEGF, FGF-2) or by exercise training. The critical role of NO in therapeutic arteriogenesis is independent of NO-mediated changes in vascular conductance and implies a central role in arteriogenic signaling events. Maintenance, or improvement, of NO production and signaling, such as with regular exercise, may improve endothelial cell function and thus may help preserve the arteriogenic potential of preexisting collateral networks.

Effect of the slow-component rise in oxygen uptake on VO2max

During constant-rate high-intensity (CRHI) exercise lasting longer than 3 min, VO2 has been reported to exceed VO2max measured with a traditional graded exercise test (GXT). This could be because VO2max was not achieved on the GXT or because the factors responsible for the slow-component rise in VO2 alter VO2max. The objective of this study was to test the hypothesis that the slow-component rise in VO2 measured during CRHI running leads to a total VO2 that exceeds VO2max measured during a running GXT. VO2max was determined in eight highly trained individuals using data collected from five grade-incremented, treadmill-running GXT. Each subject demonstrated a definitive plateau of VO2 as a function of exercise intensity. Three VO2max values based on different approaches for representing the VO2max plateau were obtained. Subjects also completed two exhaustive CRHI bouts of treadmill running lasting 7-13 min at speeds estimated from the ACSM equation to elicit an average of 99 +/- 5% VO2max. The mean (+/- SD) VO2peak determined during the CRHI runs (4.17 +/- 0.9 l.min-1) was not different form or less than the three VO2max values (4.19-4.32 +/- 0.09 l.min-1). We conclude that in highly trained individuals, the slow-component rise in VO2 during CRHI treadmill running does not lead to a total VO2 that exceeds the VO2max measured during a running graded exercise test.

Angiotensin Converting Enzyme Inhibition Enhances Collateral Artery Remodeling in Rats With Femoral Artery Occlusion

Evidence from experimental animal studies indicate that ACE inhibition expands collateral blood flow both in ischemic hearts and peripheral limbs. The present study evaluates whether ACE inhibitor induces collateral blood flow expansion and change of angiogenic gene expression profile in collateral arteries during remodeling. Male Sprague-Dawley rats, weighing 350 g were treated with vehicle (control) or quinapril (ACE inhibitor) at either low dose (3.0 mg/kg) or high dose (18 mg/kg) for 1, 3, 7, 14 days (gene expression) or 16 days (blood flow). All rats received bilateral occlusions of the femoral arteries. Collateral blood flow to the hind limb was assessed by 85Sr and 141Ce-labeled microspheres during treadmill running at 15 and 25 m/min speeds. Quinapril reduced plasma ACE activity by 58% and 88% for the low-dose and high-dose groups, respectively (P < 0.001). High-dose quinapril reduced exercising blood pressure (P < 0.05) and increased hind limb conductance. Collateral blood flows to calf muscles were 51 ± 3.7, 73 ± 5.0, and 68 ± 1.9 mL/min per 100 g in control and quinapril low- and high-dose groups, respectively, during high-speed running (P < 0.001). Real-time RT-PCR revealed that ACE inhibition shifted gene expression to a proangiogenic phenotype in the newly developed collateral arteries. Our findings indicate that ACE inhibition could increase collateral-dependent blood flow and collateral vessel remodeling by promoting proangiogenic gene expression in newly developed collateral arteries. Our results support the potential utility of ACE inhibitor as a therapeutic agent in treating peripheral occlusive arterial disease.

ANAEROBIC CAPACITY AND MUSCLE ACTIVATION DURING HORIZONTAL AND UPHILL RUNNING61

Anaerobic capacity as measured by the maximal or peak oxygen deficit is greater during uphill than during horizontal running. The objective of this study was to determine whether the greater peak oxygen deficit determined during uphill compared with horizontal running is related to greater muscle volume or mass activated in the lower extremity. The peak oxygen deficit in 12 subjects was determined during supramaximal treadmill running at 0 and 10% grade. Exercise-induced contrast shifts in magnetic resonance images were obtained before and after exercise and used to determine the percentage of muscle volume activated. The mean peak oxygen deficit determined for uphill running [2.96 +/- 0.63 (SD) liters or 49 +/- 6 ml/kg] was significantly greater (P < 0.05) than for horizontal running (2.45 +/- 0.51 liters or 41 +/- 7 ml/kg) by 21%. The mean percentage of muscle volume activated for uphill running [73.1 +/- 7. 4% (SD)] was significantly greater (P < 0.05) than for horizontal running (67.0 +/- 8.3%) by 9%. The differences in peak oxygen deficit (liters) between uphill and horizontal running were significantly related (y = 8.05 x 10(-4)x + 0.35; r = 0.63, SE of estimate = 0.29 liter, P < 0.05) to the differences in the active muscle volume (cm3) in the lower extremity. We conclude that the higher peak oxygen deficit during uphill compared with horizontal running is due in part to increased mass of skeletal muscle activated in the lower extremity.

MR MEASUREMENTS OF MUSCLE DAMAGE AND ADAPTATION AFTER ECCENTRIC EXERCISE

The purposes of this study were, first, to clarify the long-term pattern of T2 relaxation times and muscle volume changes in human skeletal muscle after intense eccentric exercise and, second, to determine whether the T2 response exhibits an adaptation to repeated bouts. Six young adult men performed two bouts of eccentric biceps curls (5 sets of 10 at 110% of the 1-repetition concentric maximum) separated by 8 wk. Blood samples, soreness ratings, and T2-weighted axial fast spin-echo magnetic resonance images of the upper arm were obtained immediately before and after each bout; at 1, 2, 4, 7, 14, 21, and 56 days after bout 1; and at 2, 4, 7 and 14 days after bout 2. Resting muscle T2 [27.6 +/- 0.2 (SE) ms] increased immediately postexercise by 8 +/- 1 ms after both bouts. T2 peaked 7 days after bout 1 at 47 +/- 4 ms and remained elevated by 2.5 ms at 56 days. T2 peaked lower (37 +/- 4 ms) and earlier (2-4 days) after bout 2, suggesting an adaptation of the T2 response. Peak serum creatine kinase values, pain ratings, and flexor muscle swelling were also significantly lower after the second bout (P < 0.05). Total volume of the imaged arm region increased transiently after bout 1 but returned to preexercise values within 2 wk. The exercised flexor compartment swelled by over 40%, but after 2 wk it reverted to a volume 10% smaller than that before exercise and maintained this volume loss through 8 wk, consistent with partial or total destruction of a small subpopulation of muscle fibers.