Aging induces muscle-specific impairment of endothelium-dependent dilation in skeletal muscle feed arteries

Abstract

. Aging induces muscle-specific impairment of endothelium-dependent dilation in skeletal muscle feed arteries. J Appl Physiol 93: 1685-1690, 2002; 10.1152/ japplphysiol.00461.2002.-We tested the hypothesis that aging decreases endothelium-dependent vasodilation in feed arteries perfusing rat skeletal muscle. In addition, we tested the hypothesis that attenuated vasodilator responses are associated with decreased endothelial nitric oxide synthase (eNOS) and superoxide dismutase-1 (SOD-1) expression. Soleus feed arteries (SFA) and gastrocnemius feed arteries (GFA) were isolated from young (4 mo) and old (24 mo) male Fischer 344 rats. Feed arteries from the right hindlimb were cannulated with two glass micropipettes for examination of endothelium-dependent [acetylcholine (ACh)] and endothelium-independent [adenosine (Ado) or sodium nitroprusside (SNP)] vasodilator function. Feed arteries from the left hindlimb were frozen and used to assess eNOS and SOD-1 protein and mRNA expression. In SFA, endothelium-dependent dilation to ACh was reduced in old rats (0.9 Ϯ 0.04 vs. 0.8 Ϯ 0.03), whereas dilator responses to Ado and SNP were similar in SFA of young and old rats. In GFA, vasodilator responses to ACh, Ado, and SNP were not altered by age. eNOS and SOD-1 protein expression declined with age in SFA (Ϫ71 and Ϫ54%, respectively) but not in GFA. eNOS and SOD-1 mRNA expression were not altered by age in SFA or GFA. Collectively, these data indicate aging induces muscle-specific impairment of endothelium-dependent vascular function in SFA. endothelial nitric oxide synthase; superoxide dismutase; nitric oxide; acetylcholine; sodium nitroprusside RESULTS FROM SEVERAL STUDIES indicate that endothelial function in conduit arteries declines with age in humans and animals (3,4,7,8,10,11,16,23). The endothelial dysfunction induced by aging is characterized by blunted vasodilator responses of conduit arteries to select endothelium-dependent agonists (3,4,7,8,10,11,16,23). The mechanism(s) for the detrimental effects of age on endothelium-dependent dilation is not fully understood; however, age-associated decrements in the ability of endothelial cells to produce and/or release nitric oxide (NO) may contribute to the dysfunction (3,11,16). This speculation is supported by experimental evidence indicating that vasodilation in response to ACh and bradykinin is impaired in aorta from senescent subjects, whereas dilation to sodium nitroprusside (SNP) is not compromised (3,5,16).An age-associated decline in the expression of endothelial NO synthase (eNOS), decreasing local production of NO, is one mechanism that may contribute to impaired endothelium-mediated dilation in conduit arteries of senescent animals. Indeed, age-related reductions eNOS mRNA expression have been reported in aorta of senescent rats (3, 6). Alternatively, decreased expression of Cu/Zn-dependent superoxide dismutase (SOD-1) may contribute to impaired endothelium-mediated dilation by compromising the ability to scavenge superoxide anion (O 2 Ϫ ⅐), decreasing the bio...

Aging impairs flow-induced dilation in coronary arterioles: role of NO and H2O2

“…Previous studies have indicated that NO-mediated endothelial function declines with advancing age (26,43,49), and recent reports have shown a similar impairment in endothelium-mediated vasodilation in the coronary microvasculature (7,21). In the present study, we have demonstrated for the first time an age-induced decline in flow-induced NO production, as evidenced by diminished DAF fluorescence in isolated coronary arterioles of aged rats (Fig.…”

The Effects of Aging on Capillary Hemodynamics in Contracting Rat Spinotrapezius Muscle

“…This may represent a reduction in the reserve capacity of one or more vasoregulatory pathways (i.e. endothelium-independent dilation) in preference to dilatory function per se as reported by others (Muller-Delp et al, 2002b;Woodman et al, 2002). The combination of these impaired vasoregulatory mechanisms is likely to require higher strength contractions to increase arteriolar flow above resting values and, importantly, will significantly compromise the reserve capacity to increase arteriolar flow during maximal exercise.…”

“…For example, aging is associated with reductions in functional sympatholysis (Dinenno et al, 2005;Parker et al, 2007), myogenic control (Muller-Delp et al, 2002a), and contraction-induced rapid vessel relaxation (Carlson et al, 2008). Moreover, endothelium-dependent vasodilation is impaired (Muller-Delp et al, 2002b), with the dysfunction likely occurring preferentially in arterioles supplying oxidative but not glycolytic muscles (Woodman et al, 2002). While several discrete signaling pathways contribute to the endothelium-dependent regulation of vascular tone, NO appears to play a principal role, particularly in oxidative muscles (Hirai et al, 1994).…”

“…It is wellestablished that the NO-mediated dilation is reduced in aged vessels when compared to younger counterparts. For example, aging reduces NO-mediated vasodilation in response to contractions in the skeletal muscles of humans (Taddei et al, 2000;Schrage et al, 2007) and rats (Muller-Delp et al, 2002b;Woodman et al, 2002;Spier et al, 2004).…”

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

“…Power analyses indicate that a doubled sample size is required to achieve statistical significance in this instance. Furthermore, we studied the vastus lateralis alone; therefore, our results are only reflective of a mixed fiber type muscle bed and do not rule out the possibility that vascular abnormalities exist in highly oxidative muscle beds of healthy aged individuals, as has been demonstrated in rodent models (46,66). As norepinephrine and phentolamine are nonselective ␣-adrenergic agonists and an-tagonists, respectively, these results do not preclude a possible differential effect of aging on ␣ 1 -or ␣ 2 -adrenergic-mediated blood flow regulation.…”