Key points• Increases in aerobic capacity and intramuscular triglyceride (IMTG) utilization are well-described adaptations to endurance training (ET) and contribute to improvements in insulin sensitivity.• Sprint interval training (SIT) also improves aerobic capacity and insulin sensitivity with a lower time commitment than ET.• This study aimed to determine whether SIT also induces improvements in insulin sensitivity and net IMTG breakdown, and to investigate the underlying mechanisms.• Six weeks of ET and SIT increased net IMTG breakdown during moderate-intensity cycling, and improved insulin sensitivity. A greater concentration of lipid droplet-associated proteins, perilipin 2 and perilipin 5, was observed following both training modes and contributes to the increases in net IMTG breakdown following training.• The results suggest a novel mechanism for the training-induced improvements in IMTG breakdown and insulin sensitivity, and clearly demonstrate that SIT is an alternative, time-efficient training strategy that induces similar beneficial metabolic adaptations. Abstract Intramuscular triglyceride (IMTG) utilization is enhanced by endurance training (ET)and is linked to improved insulin sensitivity. This study first investigated the hypothesis that ET-induced increases in net IMTG breakdown and insulin sensitivity are related to increased expression of perilipin 2 (PLIN2) and perilipin 5 (PLIN5). Second, we hypothesized that sprint interval training (SIT) also promotes increases in IMTG utilization and insulin sensitivity.Sixteen sedentary males performed 6 weeks of either SIT (4-6, 30 s Wingate tests per session, 3 days week −1 ) or ET (40-60 min moderate-intensity cycling, 5 days week −1 ). Training increased resting IMTG content (SIT 1.7-fold, ET 2.4-fold; P < 0.05), concomitant with parallel increases in PLIN2 (SIT 2.3-fold, ET 2.8-fold; P < 0.01) and PLIN5 expression (SIT 2.2-fold, ET 3.1-fold; P < 0.01). Pre-training, 60 min cycling at ∼65% pre-trainingV O 2 peak decreased IMTG content in type I fibres (SIT 17 ± 10%, ET 15 ± 12%; P < 0.05). Following training, a significantly greater breakdown of IMTG in type I fibres occurred during exercise (SIT 27 ± 13%, ET 43 ± 6%; P < 0.05), with preferential breakdown of PLIN2-and particularly PLIN5-associated lipid droplets. Training increased the Matsuda insulin sensitivity index (SIT 56 ± 15%, ET 29 ± 12%; main effect P < 0.05). No training × group interactions were observed for any variables. In conclusion, SIT and ET both increase net IMTG breakdown during exercise and increase in PLIN2 and PLIN5 protein expression. The data are consistent with the hypothesis that increases in PLIN2 and PLIN5 are related to the mechanisms that promote increased IMTG utilization during exercise and improve insulin sensitivity following 6 weeks of SIT and ET.

Key point• Optimal vascular function is critical for health, and endurance training (ET) has previously been shown to be an effective method of improving this.• Sprint interval training (SIT) has been proposed as a time efficient alternative to ET but its effect on skeletal muscle microvasculature has not been studied and no direct comparison with ET has been made.• ET and SIT in this study were equally effective at decreasing arterial stiffness and increasing skeletal muscle capillarisation and eNOS content.• The main results suggest that both training modes improve skeletal muscle microvascular and macrovascular function, with SIT being a time efficient alternative.Abstract Sprint interval training (SIT) has been proposed as a time efficient alternative to endurance training (ET) for increasing skeletal muscle oxidative capacity and improving certain cardiovascular functions. In this study we sought to make the first comparisons of the structural and endothelial enzymatic changes in skeletal muscle microvessels in response to ET and SIT. Sixteen young sedentary males (age 21 ± SEM 0.7 years, BMI 23.8 ± SEM 0.7 kg m −2 ) were randomly assigned to 6 weeks of ET (40-60 min cycling at ∼65%V O 2 peak, 5 times per week) or SIT (4-6 Wingate tests, 3 times per week). Muscle biopsies were taken from the m. vastus lateralis before and following 60 min cycling at 65%V O 2 peak to measure muscle microvascular endothelial eNOS content, eNOS serine 1177 phosphorylation, NOX2 content and capillarisation using quantitative immunofluorescence microscopy. Whole body insulin sensitivity, arterial stiffness and blood pressure were also assessed. ET and SIT increased skeletal muscle microvascular eNOS content (ET 14%; P < 0.05, SIT 36%; P < 0.05), with a significantly greater increase observed following SIT (P < 0.05). Sixty minutes of moderate intensity exercise increased eNOS ser 1177 phosphorylation in all instances (P < 0.05), but basal and post-exercise eNOS ser 1177 phosphorylation was lower following both training modes. All microscopy measures of skeletal muscle capillarisation (P < 0.05) were increased with SIT or ET, while neither endothelial nor sarcolemmal NOX2 was changed. Both training modes reduced aortic stiffness and increased whole body insulin sensitivity (P < 0.05). In conclusion, in sedentary males SIT and ET are effective in improving muscle microvascular density and eNOS protein content.

Key pointsr Skeletal muscle capillary density and vasoreactivity are reduced in obesity, due to reduced nitric oxide bioavailability.r Sprint interval training (SIT) has been proposed as a time efficient alternative to moderate-intensity continuous training (MICT), but its effect on the skeletal muscle microvasculature has not been studied in obese individuals.r We observed that SIT and MICT led to equal increases in capillarisation and endothelial eNOS content, while reducing endothelial NOX2 content in microvessels of young obese men.r We conclude that SIT is equally effective at improving skeletal muscle capillarisation and endothelial enzyme balance, while being a time efficient alternative to traditional MICT.Abstract Sprint interval training (SIT) has been proposed as a time efficient alternative to moderate-intensity continuous training (MICT), leading to similar improvements in skeletal muscle capillary density and microvascular function in young healthy humans. In this study we made the first comparisons of the muscle microvascular response to SIT and MICT in an obese population. Sixteen young obese men (age 25 ± 1 years, BMI 34.8 ± 0.9 kg m −2 ) were randomly assigned to 4 weeks of MICT (40-60 min cycling at ß65%V O 2 peak , 5 times per week) or constant load SIT (4-7 constant workload intervals of 200% W max 3 times per week). Muscle biopsies were taken before and after training from the m. vastus lateralis to measure muscle microvascular endothelial eNOS content, eNOS serine 1177 phosphorylation, NOX2 content and capillarisation using quantitative immunofluorescence microscopy. Maximal aerobic capacity (V O 2 peak ), whole body insulin sensitivity and arterial stiffness were also assessed. SIT and MICT increased skeletal muscle microvascular eNOS content and eNOS ser 1177 phosphorylation in terminal arterioles and capillaries (P < 0.05), but the latter effect was eliminated when normalised to eNOS content (P = 0.217). SIT and MICT also reduced microvascular endothelial NOX2 content (P < 0.05) and both increased capillary density and capillary-fibre perimeter exchange index (P < 0.05). In parallel, SIT and MICT increasedV O 2 peak (P < 0.05) and whole body insulin sensitivity (P < 0.05), and reduced central artery stiffness (P < 0.05). As no significant differences were observed between SIT and MICT it is concluded that SIT is a time efficient alternative to MICT to improve aerobic capacity, insulin sensitivity and muscle capillarisation and endothelial eNOS/NAD(P)Hoxidase protein ratio in young obese men.

Abstract-The initial view of the renin-angiotensin system focused on the role of angiotensin II as a hormone involved in blood pressure control, based on its role in renal salt and water regulation, as well as central nervous system (thirst) and vascular smooth muscle tone. Subsequent data showed a role for angiotensin II in long-term effects on cardiovascular structure, including cardiac hypertrophy and vascular remodeling. I n this review, we discuss the evolving role of angiotensin II (Ang II) as a regulator of endothelial cell (EC) function. In particular, recent clinical trials of angiotensin-converting enzyme (ACE) inhibitors and Ang II receptor blockers (ARBs) suggest that several of the beneficial effects of these drugs are mediated by inhibiting Ang II effects at the endothelium. Initially, Ang II was identified as a hormone that controlled blood pressure based on regulation of renal salt and water metabolism, central nervous system mechanisms (thirst and sympathetic outflow), and vascular smooth muscle cell (VSMC) tone. 1 Later, Ang II was found to exert long-term effects on tissue structure, including cardiac hypertrophy, vascular remodeling, and renal fibrosis. Importantly, recent human studies with ACE inhibitors and ARBs have yielded exciting clinical benefits such as decreased incidence of stroke, diabetes mellitus, and end-stage renal disease. 2,3 This article discusses the endothelium-specific effects of these drugs and Ang II, based on the concept of diverse signals and effects mediated by multiple angiotensin receptors (AT 1 R, AT 2 R, and AT 4 R), multiple angiotensin I-and Ang II-derived peptides [Ang III, Ang IV, and Ang (1-7)], and vascular bed-specific events (Figure 1). The enzymes that control generation of these peptides, including ACE, ACE2, endopeptidases, and aminopeptidases, interact with each other. In addition, drugs such as ACE inhibitors and ARBs that inhibit formation of Ang II and binding to its receptor also modify the expression of receptors for Ang II and of other vasoactive hormones, including bradykinin and adrenomedullin. This complex interplay of pathways helps to explain the findings that Ang II can have both beneficial and detrimental effects on vascular function. Effects of Angiotensin Type-1 ReceptorThe AT 1 R has been shown to mediate most of the physiological actions of Ang II. However, as discussed, important regulatory roles for the AT 2 R and AT 4 R, have been defined, especially in EC. Recent data show several pathways by which the AT 1 R and AT 2 R modulate EC function. 4 ApoptosisAng II has been shown both to increase and decrease EC apoptosis, suggesting that other factors influence the actions of Ang II (eg, presence of oxidized low-density lipoprotein [oxLDL]). In fact, both the AT 1 R and the AT 2 R have been suggested to mediate EC apoptosis. 5,6 As discussed further, we speculate that the relative AT 1 R and AT 2 R expression levels are important determinants of the effects of Ang II in EC (Figure 2). Ang II-mediated EC apoptosis is in part mediated b...

Even for employed problem drinkers who are not abusing drugs and who have no serious medical problems, an initial referral to AA alone or a choice of programs, although less costly than inpatient care, involves more risk than compulsory inpatient treatment and should be accompanied by close monitoring for signs of incipient relapse.