Aging induces a progressive decline in vasoconstrictor responses in central and peripheral arteries. This study investigated the hypothesis that vascular smooth muscle (VSM) contractile function declines with age in soleus muscle feed arteries (SFA). Contractile function of cannulated SFA isolated from young (4 months) and old (24 months) Fischer 344 rats was assessed by measuring constrictor responses of denuded (endothelium removed) SFA to norepinephrine (NE), phenylephrine (PE), and angiotensin II (Ang II). In addition, we investigated the role of RhoA signaling in modulation of VSM contractile function. Structural and functional characteristics of VSM cells were evaluated by fluorescence imaging and atomic force microscopy (AFM). Results indicated that constrictor responses to PE and Ang II were significantly impaired in old SFA, whereas constrictor responses to NE were preserved. In the presence of a Rho-kinase inhibitor (Y27632), constrictor responses to NE, Ang II, and PE were significantly reduced in young and old SFA. In addition, the age-group difference in constrictor responses to Ang II was eliminated. ROCK1 and ROCK2 content was similar in young and old VSM cells, whereas pROCK1 and pROCK2 were significantly elevated in old VSM cells. Aging was associated with a reduction in smooth muscle α-actin stress fibers and recruitment of proteins to cell-matrix adhesions. Old VSM cells presented an increase in integrin adhesion to the matrix and smooth muscle γ-actin fibers that was associated with increased cell stiffness. In conclusion, our results indicate that VSM contractile function declined with age in SFA. The decrement in contractile function was mediated in part by RhoA/ROCK signaling. Upregulation of pROCK in old VSM cells was not able to rescue contractility in old SFA. Collectively, these results indicate that changes at the VSM cell level play a central role in the reduced contractile function of aged SFA.
Aging is associated with impaired vascular function characterized in part by attenuated vasorelaxation to acetylcholine (ACh) and sodium nitroprusside (SNP). Due to structural and functional differences between conduit and resistance arteries, the effect of aging on vasorelaxation responses may vary along the arterial tree. Our purpose was to determine age‐related differences in vasorelaxation responses in large and small arteries. Responses to the endothelium‐dependent vasodilator acetylcholine (ACh) and the endothelium‐independent vasodilator sodium nitroprusside (SNP) were assessed in abdominal aorta (AA), iliac arteries (IA), femoral arteries (FA), and gastrocnemius feed arteries (GFA) from young and old male rats. ACh‐mediated vasorelaxation was significantly impaired in old AA and IA. SNP‐mediated vasorelaxation was impaired in old AA. To investigate a potential mechanism for impaired relaxation responses in AA and IA, we assessed eNOS protein content and interactions with caveolin‐1 (Cav‐1), and calmodulin (CaM) via immunoprecipitation and immunoblot analysis. We found no age differences in eNOS content or interactions with Cav1 and CaM. Combined data from all rats revealed that eNOS content was higher in IA compared to AA and FA (p < .001), and was higher in GFA than AA (p < .05). Cav1:eNOS interaction was greater in FA than in AA and IA (p < .01), and in GFA compared to IA (p < .05). No differences in CaM:eNOS were detected. In conclusion, age‐related impairment of vasorelaxation responses occurred in the large conduit, but not small conduit or resistance arteries. These detrimental effects of age were not associated with changes in eNOS or its interactions with Cav‐1 or CaM.
Arterial aging results in a progressive reduction in elasticity of the vessel wall and an impaired ability of aged blood vessels to control local blood flow and pressure. Recently, a new concept has emerged that the stiffness and decreased contractility of vascular smooth muscle (VSM) cells are important contributors to age-induced arterial dysfunction. This study investigated the hypothesis that aging alters integrin function in a matrix stiffness-dependent manner, which contributes to decreased VSM contractility in aged soleus muscle feed arteries (SFA). The effect of RGD-binding integrins on contractile function of cannulated SFA isolated from young (4 months) and old (24 months) Fischer 344 rats was assessed by measuring constrictor responses to norepinephrine, phenylephrine, and angiotensin II. Results indicated that constrictor responses in presence of RGD were impaired in old compared to young SFA. VSM cells isolated from young and old SFA were used for functional experiments using atomic force microscopy and high-resolution imaging. Aging was associated with a modulation of integrin β1 recruitment at cell-matrix adhesions that was matrix and substrate stiffness dependent. Our data showed that substrate stiffening drives altered integrin β1 expression in aging, while soft substrates abolish age-induced differences in overall integrin β1 expression. In addition, substrate stiffness and matrix composition contribute to the modulation of SMα-actin cytoskeleton architecture with soft substrates reducing age effects. Our results provide new insights into age-induced structural changes at VSM cell level that translates to decreased functionality of aged resistance soleus feed arteries.
Background Antioxidant supplementation may provide protection against negative health consequences of oxygen-free radicals caused by aerobic and re-sustained exercise. The aim is to find out the efficacy of antioxidant rich nutrient bar supplementation on the antioxidant status and physical fitness components of athletes. Method Forty track and field athletes were selected using convenience sampling technique. The Human Research Ethics Committee of PSG College of Arts and Science, Coimbatore approved the study. Voluntary participation of the subjects was emphasized and a written consent was obtained from them in order to be included in the study. An interview schedule was formulated to collect general information such as name, age, gender, and academic qualifications, as well as information pertaining to the types of sporting activity, duration of the activity per day, number of years involved in the respective sports and level of participation (district/state/national). Nutrient bars each weighing 50gm were prepared with rolled oats, pumpkin seeds, dehydrated carrots, flax seeds, peanuts, almonds, honey and date syrup as ingredients. Each athlete was provided with two bars containing 110 mg of antioxidant. The prepared bars were analyzed for their total anti-oxidant content using DPPH method. The experimental group (n = 20) was supplemented with the formulated nutrient bars every day for a period of 3 months, and the control group (n = 20) with a placebo. Bio-chemical parameters namely GSH, GSH-px, SOD, vitamin C, serum LPO and physical fitness tests such as 12 minutes test, speed test, step test, push-ups test, vertical jump test and hexagon agility test were assessed at baseline and after 90 days. Statistical analysis was performed using SPSS (version 15). ResultsThe mean age was 18 ± 3.2 yrs. Sixty percent of the selected athletes were males and 40 % females. The main source of nutrition information was from coaches (56 %) and magazines (30 %). The athletes of the experimental group, when compared with the control group, showed a significant increase in serum levels from 37.42 ± 12.01 units/min/ml to 42.08 ± 13.16 units/min/ml of SOD (p = 0.000). LPO increased from 2.89 ± 0.82 μg/ml to 3.80 ± 1.37 μg/ml (p = 0.005), GSH increased from 209.76 ± 8.17 μg/ml to 244.58 ± 33.36 μg/ml (p = 0.000). The mean levels of vitamin C and GSH-px decreased minimally in the experimental group but significantly in the control group. Significant improvement in all six physical fitness tests namely 12 minutes test (from 1.44 ± 0.142 to 1.56 ± 0.134) , speed test (from 6.5940 ± 0.258 to 6.7435 ± 0.25) step test (from 68.65 ± 5.51 to 78.35 ± 4.004) push-ups (from 22.25 ± 3.97 to 29.70 ± 3.40), vertical jumps test (from 60.00 ± 5.620 to 63.75 ± 6.043) and hexagon agility tests (from 12.255 ± 0.42 to 12.400 ± 0.51) were observed in the experimental group). However in the control group, the improvements were significant only in the 12 minutes test, step test and speed test. Conclusion Supplementation of athletes with antioxidant-rich...
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