Aging alters the contribution of nitric oxide to regional muscle hemodynamic control at rest and during exercise in rats

Abstract

Advanced age is associated with altered skeletal muscle hemodynamic control during the transition from rest to exercise. This study investigated the effects of aging on the functional role of nitric oxide (NO) in regulating total, inter-, and intramuscular hindlimb hemodynamic control at rest and during submaximal whole body exercise. We tested the hypothesis that NO synthase inhibition (N(G)-nitro-l-arginine methyl ester, l-NAME; 10 mg/kg) would result in attenuated reductions in vascular conductance (VC) primarily in oxidative muscles in old compared with young rats. Total and regional hindlimb muscle VCs were determined via radiolabeled microspheres at rest and during treadmill running (20 m/min, 5% grade) in nine young (6-8 mo) and seven old (27-29 mo) male Fisher 344 × Brown Norway rats. At rest, l-NAME increased mean arterial pressure (MAP) significantly by ∼17% and 21% in young and old rats, respectively. During exercise, l-NAME increased MAP significantly by ∼13% and 19% in young and old rats, respectively. Compared with young rats, l-NAME administration in old rats evoked attenuated reductions in 1) total hindlimb VC during exercise (i.e., down by ∼23% in old vs. 43% in young rats; P < 0.05), and 2) VC in predominantly oxidative muscles both at rest and during exercise (P < 0.05). Our results indicate that the dependency of highly oxidative muscles on NO-mediated vasodilation is markedly diminished, and therefore mechanisms other than NO-mediated vasodilation control the bulk of the increase in skeletal muscle VC during the transition from rest to exercise in old rats. Reduced NO contribution to vasomotor control with advanced age is associated with blood flow redistribution from highly oxidative to glycolytic muscles during exercise.

Sex differences with aging in nutritive skeletal muscle blood flow: impact of exercise training, nitric oxide, and α-adrenergic-mediated mechanisms

“…The present study demonstrates a preserved ACh-stimulated vasodilatory response and an equivalent vasodilatory response to an NO donor (SNP) in aged compared with young individuals, indicating preservation of endothelial function with coincident preserved NOS activity levels. Additionally, NOS inhibition with L-NMMA had similar effects on nutritive blood flow between age groups, which is consistent with the previous observation of similar total resting hindlimb vascular conductance and responses to NOS inhibition between young and old rats (28). Collectively, the Fig.…”

Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles

“…This flow redistribution is mediated, at least in part, by diminished NO contribution in the vasculature of highly oxidative muscles (20). Our present data would suggest that this loss of NO contribution may be due, in part, to the loss of authentic NO, but may also be due to the loss of vasodilation mediated by other sources of NO, namely ONOO Ϫ .…”

Effects of neuronal nitric oxide synthase inhibition on microvascular and contractile function in skeletal muscle of aged rats

“…This shift in the muscle NOS isoform profile with aging is hallmarked by oxidative stress and endothelial dysfunction (14,24,26,54,59,61,65), which likely contribute to exercise intolerance in this population (47).…”