Advancing age alters the structural and functional determinants of convective and diffusive muscle oxygen (O 2 ) flux. However, capillary red blood cell (RBC) hemodynamics have not been investigated during contractions in muscles of old animals. PURPOSE:To test the hypothesis that aging induces significant alterations in capillary hemodynamics during electrically-induced contractions in the spinotrapezius muscle of old Fischer 344 x Brown Norway rats when compared to younger counterparts.

Aged rats exhibit a decreased muscle microvascular O(2) partial pressure (Pmv(O(2))) at rest and during contractions compared with young rats. Age-related reductions in nitric oxide bioavailability due, in part, to elevated reactive O(2) species, constrain muscle blood flow (Qm). Antioxidants may restore nitric oxide bioavailability, Qm, and ameliorate the reduced Pmv(O(2)). We tested the hypothesis that antioxidants would elevate Qm and, therefore, Pmv(O(2)) in aged rats. Spinotrapezius muscle Pmv(O(2)) and Qm were measured, and oxygen consumption (Vm(O(2))) was estimated in anesthetized male Fisher 344 x Brown Norway hybrid rats at rest and during 1-Hz contractions, before and after antioxidant intravenous infusion (76 mg/kg vitamin C and 52 mg/kg tempol). Before infusion, contractions evoked a biphasic Pmv(O(2)) that fell from 30.6 +/- 0.9 Torr to a nadir of 16.8 +/- 1.2 Torr with an "undershoot" of 2.8 +/- 0.7 Torr below the subsequent steady-state (19.7 +/- 1.2 Torr). The principal effect of antioxidants was to elevate baseline Pmv(O(2)) from 30.6 +/- 0.9 to 35.7 +/- 0.8 Torr (P < 0.05) and reduce or abolish the undershoot (P < 0.05). Antioxidants reduced Qm and Vm(O(2)) during contractions (P < 0.05), while decreasing force production 16.5% (P < 0.05) and elevating the force production-to-Vm(O(2)) ratio (0.92 +/- 0.03 to 1.06 +/- 0.6, P < 0.05). Thus antioxidants increased Pmv(O(2)) by altering the balance between muscle O(2) delivery and Vm(O(2)) at rest and during contractions. It is likely that this effect arose from antioxidants reducing myocyte redox below the level optimal for contractile performance and directly (decreased tension) or indirectly (altered balance of vasoactive mediators) influencing O(2) delivery and Vm(O(2)).

Aging-induced alterations in peripheral circulatory control during contractions reduce the microvascular partial pressure of O(2) (P(O)(2)mv; which reflects the dynamic balance in the O(2) delivery-to-O(2) uptake ratio), resulting in exaggerated intramuscular metabolic disturbances and premature fatigue. However, the extent to which this altered P(O)(2)mv during contractions is associated with prolongated muscle metabolic recovery is not known. We tested the hypothesis that the aging-induced speeding of the P(O)(2)mv on-kinetics would presage slowed P(O)(2)mv off-kinetics. The spinotrapezius muscle was exposed in six young (6-8 months) and seven old (26-28 months) male Fischer 344xBrown Norway F1-hybrid rats. The P(O)(2)mv kinetic profile was measured via phosphorescence quenching at rest, during electrically stimulated contractions (1Hz, 7-9V, 2ms pulse duration, 180s), and throughout recovery (180s). Aged rats which evidenced faster P(O)(2)mv on-kinetics (reduced mean response time (MRTon), young: 27.3+/-3.6s, old: 19.2+/-1.6s; P<0.05) exhibited markedly slowed P(O)(2)mv off-kinetics (increased MRToff, young: 46.5+/-5.9s, old: 84.8+/-7.9s; P<0.05). Accordingly, a greater degree of P(O)(2)mv on-off asymmetry (MRToff-MRTon) in the aged muscle was observed (young: 19.1+/-4.5s, old: 65.6+/-8.6s; P<0.01). We conclude that aging-induced speeding of the P(O)(2)mv on-kinetics does indeed presage a slowed P(O)(2)mv off-kinetics, which likely compromises muscle metabolic recovery and may reduce subsequent contractile performance. Moreover, the greater degree of P(O)(2)mv on-off asymmetry in the aged muscle suggests a mechanistic link between impaired microvascular oxygenation and altered muscle metabolic responses during exercise transitions.

Alterations of skeletal muscle redox state via antioxidant supplementation have the potential to impact contractile function and vascular smooth muscle tone. The effects of antioxidants on the regulation of muscle O 2 delivery-O 2 utilization (Q O 2 m /V O 2 m ) matching (which sets the microvascular partial pressure of O 2 ; P O 2 mv ) in young healthy muscle are not known. Therefore, the purpose of this study was to test the effects of acute antioxidant supplementation on rat spinotrapezius muscle force production, blood flow,V O 2 m and P O 2 mv (phosphorescence quenching). Anaesthetized male Fischer 344 × Brown Norway rats (6-8 months old) had their right spinotrapezius muscles either exposed for measurement of blood flow and P O 2 mv (n = 13) or exteriorized for measurement of muscle force production (n = 6). Electrically stimulated 1 Hz twitch contractions (∼7-9 V) were elicited for 180 s, and measurements were made before and after acute intra-arterial antioxidant supplementation (76 mg kg −1 ascorbic acid, 52 mg kg −1 tempol) dissolved in saline and infused over 30 min. The principal effects of antioxidants were a ∼25% decrease (P < 0.05) in contracting spinotrapezius muscle force production concurrent with reductions in muscle blood flow andV O 2 m at rest and during contractions (P < 0.05 for both). Antioxidant supplementation reduced the resting baseline P O 2 mv (before, 29.9 ± 1.2 mmHg; after, 25.6 ± 1.3 mmHg; P < 0.05), and this magnitude of depression was sustained throughout the rest-to-exercise transition (steady-state value before, 16.4 ± 0.7 mmHg; after, 13.6 ± 0.9 mmHg; P < 0.05). In addition, the time constant of the P O 2 mv decrease was reduced after antioxidant supplementation (before, 23.4 ± 4.3 s; after, 15.6 ± 2.7 s; P < 0.05). These results demonstrate that antioxidant supplementation significantly impacts the control ofQ O 2 m /V O 2 m in young rats at rest and during contractions.

Advancing age alters the structural and functional determinants of convective and diffusive muscle oxygen (O 2 ) flux. However, capillary red blood cell (RBC) hemodynamics have not been investigated during contractions in muscles of old animals. PURPOSE:To test the hypothesis that aging induces significant alterations in capillary hemodynamics during electrically-induced contractions in the spinotrapezius muscle of old Fischer 344 x Brown Norway rats when compared to younger counterparts.