SUMMARY1. Reports that a greater natriuresis occurs after gastric rather than illtravellous sodium loads suggest that a gastric sodium monitor exists which releases a humioral natriuretic factor. As vasoactive intestinal peptide (VIP) is natriuretic, it mnight act as this mediator. To determine whether it is released from the gut inl respon-se to sodium we measured VIP levels in portal and systemic plasma of anaesthetize(d rabbits after a gastric sodium load. Levels of VIP in systemic plasma were also measured in conscious rabbits after gastric and portal sodium loads to determille the contributions of anaesthesia or increased sodium concentration in the portal tract to anv observed rise in systemic VIP levels.2. In the anaesthetized rabbit study portal and systemic VIP levels had both increased significantly from control values by 5 min after the sodium load in the low salt diet group (1' < 0-025, portal; P < 0 05, systemic). By 10 mim the levels in systemic and portal plasma were equal. 3. In the conscious rabbits an increase in systemic NVIP levels was observed inl the group on a low salt diet after a gastric but not a portal sodium load. 4. We conclude that VIP is released in response to gastric sodium loads in rabbits on low salt diets and that hepatic metabolism of V'IP is reduced in this group.

Obesity is a global epidemic and coupled with the unprecedented growth of the world’s older adult population, a growing number of individuals are both old and obese. Whilst both ageing and obesity are associated with an increased prevalence of chronic health conditions and a substantial economic burden, evidence suggests that the coincident effects exacerbate negative health outcomes. A significant contributor to such detrimental effects may be the reduction in the contractile performance of skeletal muscle, given that poor muscle function is related to chronic disease, poor quality of life and all-cause mortality. Whilst the effects of ageing and obesity independently on skeletal muscle function have been investigated, the combined effects are yet to be thoroughly explored. Given the importance of skeletal muscle to whole-body health and physical function, the present study sought to provide a review of the literature to: (1) summarise the effect of obesity on the age-induced reduction in skeletal muscle contractile function; (2) understand whether obesity effects on skeletal muscle are similar in young and old muscle; (3) consider the consequences of these changes to whole-body functional performance; (4) outline important future work along with the potential for targeted intervention strategies to mitigate potential detrimental effects.

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1. Gastric sodium loading causes release of vasoactive intestinal peptide from the gastrointestinal tract and, in rabbits on a low-sodium diet, an apparent decrease in metabolism of vasoactive intestinal peptide by the liver. Other workers have shown that decreased hepatic metabolism of vasoactive intestinal peptide is accompanied by an increase in pulmonary metabolism of vasoactive intestinal peptide. To determine whether oral sodium loading also regulates non-hepatic metabolism of vasoactive intestinal peptide, metabolic clearance studies of intravenously infused vasoactive intestinal peptide were performed. These studies were performed in male New Zealand White rabbits equilibrated on normal- and low-sodium diets before and after an acute gastric sodium load of 1.5 mmol/kg. 2. The metabolic clearance rate of vasoactive intestinal peptide was significantly greater in rabbits on the low-sodium diet than in rabbits on the normal-sodium diet both before (P less than 0.025) and after (P less than 0.05) a gastric sodium load. Significant decreases in metabolic clearance rate were observed in response to the sodium load in both dietary groups (normal-sodium diet, P less than 0.05; low-sodium diet, P less than 0.025). The theoretical secretion rate of vasoactive intestinal peptide also fell after the gastric sodium load in rabbits on the low-sodium diet (P less than 0.05) and the half-life of vasoactive intestinal peptide increased (P less than 0.01). 3. We conclude that the non-hepatic metabolism of vasoactive intestinal peptide appears to be responsive to both chronic dietary sodium intake and acute gastric sodium loading.

We have shown previously that gastric sodium loading releases vasoactive intestinal peptide from the intestine and in rabbits on a low sodium diet it appears to decrease vasoactive intestinal peptide metabolism by the liver. To determine the contributions of the low sodium diet and the acute sodium load to changes in vasoactive intestinal peptide metabolism, metabolic clearance studies of vasoactive intestinal peptide infused intraportally were performed. These studies were performed in male New Zealand white rabbits equilibrated on normal and low sodium diets before and after an acute gastric sodium load of 1.5 mmol kg-1. No difference was detectable in metabolic clearance rates between normal and low salt diets, however, decreases in metabolic clearance rates were observed in response to the sodium load (normal diet P less than 0.005, low salt P less than 0.0005). Secretion rates also decreased following the gastric sodium load (normal P less than 0.005, low salt P less than 0.05). We conclude that hepatic VIP metabolism is decreased by acute gastric sodium loading but it is not affected by chronic sodium intake.

This study examined the effect of stimulation frequency (140, 200, 230 and 260 Hz) on isometric force, work loop (WL) power, and the fatigue resistance of extensor digitorum longus (EDL) muscle (n=32), isolated from 8–10-week-old CD-1 female mice. Stimulation frequency had significant effects on isometric properties of isolated mouse EDL, whereby increasing stimulation frequency evoked increased isometric force, quicker activation, and prolonged relaxation (P &lt;0.047), until 230 Hz and above, thereafter force and activation did not differ (P &gt;0.137). Increasing stimulation frequency increased maximal WL power output (P &lt;0.001; 140 Hz, 71.3±3.5; 200 Hz, 105.4±4.1; 230 Hz, 115.5±4.1; 260 Hz, 121.1±4.1 W.kg−1), but resulted in significantly quicker rates of fatigue during consecutive WL's (P &lt;0.004). WL shapes indicate impaired muscle relaxation at the end of shortening and subsequent increased negative work appeared to contribute to fatigue at 230 and 260 Hz, but not at lower stimulation frequencies. Cumulative work was unaffected by stimulation frequency, except at the start of fatigue protocol where 230 and 260 Hz produced more work than 140 Hz (P &lt;0.039). We demonstrate that stimulation frequency affects force, power, and fatigue, but effects are not uniform between different assessments of contractile performance. Therefore, future work examining contractile properties of isolated skeletal muscle should consider increasing stimulation frequency beyond that needed for maximal force when examining maximal power but utilise a sub-maximal stimulation frequency for fatigue assessments to avoid high degree of negative work atypical of in vivo function.

SUMMARY1. In view of previous observations that the metabolism of vasoactive intestinal peptide (VIP) is significantly increased in sodium-depleted rabbits, we wished to determine whether a high sodium intake also leads to alterations in VIP metabolism.We performed metabolic clearance studies in rabbits maintained on a high sodium diet and normal control diets. These studies were performed both before and after the administration of 1-5 mmol kg-1 of sodium intravenously to observe the effects of an acute increase in body sodium.2. The rabbits maintained on the high sodium diet had a significantly lower basal plasma VIP level (P < 0 025), a lower metabolic clearance rate (MCR) of the peptide (P < 0025) and a lower secretion rate (P < 0-005), compared with the normal control animals. These differences were maintained following the intravenous sodium infusion.3. The administration of the intravenous sodium infusion resulted in a further decrease in MCR in the rabbits on the high sodium diet (P < 005).4. These results confirm that VIP metabolism is affected by high dietary intake of sodium, as well as a low sodium intake, adding further support to the hypothesis that VIP may be involved in sodium homeostasis.

The present study uniquely examined the influence of old age and adiposity on maximal concentric and eccentric torque and fatigue of the elbow (EF, EE) and knee (KF, KE) flexors and extensors. 40 males were recruited and categorised into young (n=21, 23.7±3.4) and old (n=19, 68.3±6.1) and then further into normal (young = 16.9±2.5%, old = 20.6±3.1%) and high adiposity (young = 28.9±5.0%, old = 31.3±4.2%) groups. Handgrip strength, sit-to-stand performance, and isokinetic assessments of peak torque at 60°, 120° and 180° s-1 were measured. Older men produced significantly less concentric and eccentric peak torque (P<0.016) but this was not influenced by adiposity (P>0.055). For KE and KF, high adiposity groups demonstrated reduced peak torque normalised to body mass (P<0.021), and muscle and contractile mode specific reduction in torque normalised to segmental lean mass. Eccentric fatigue resistance was unaffected by both age and adiposity (P>0.30) and perceived muscle soreness, measured up to 72 hours post, was only enhanced in the upper body of the young group following eccentric fatigue (P=0.009). Despite the impact of adiposity on skeletal muscle function being comparable between ages, these results suggest high adiposity will have greater impact on functional performance of older adults. Novelty: •Irrespective of age, high adiposity may negatively impact force to body mass ratio and muscle quality in a muscle and contractile mode specific manner. •Whilst the magnitude of adiposity effects is similar across ages, the impact for older adults will be more substantial given the age-related decline in muscle function.