To determine central and peripheral hemodynamic responses to upright leg cycling exercise, nine physically active men underwent measurements of arterial blood pressure and gases, as well as femoral and subclavian vein blood flows and gases during incremental exercise to exhaustion (Wmax). Cardiac output (CO) and leg blood flow (BF) increased in parallel with exercise intensity. In contrast, arm BF remained at 0.8 l/min during submaximal exercise, increasing to 1.2 +/- 0.2 l/min at maximal exercise (P < 0.05) when arm O(2) extraction reached 73 +/- 3%. The leg received a greater percentage of the CO with exercise intensity, reaching a value close to 70% at 64% of Wmax, which was maintained until exhaustion. The percentage of CO perfusing the trunk decreased with exercise intensity to 21% at Wmax, i.e., to approximately 5.5 l/min. For a given local Vo(2), leg vascular conductance (VC) was five- to sixfold higher than arm VC, despite marked hemoglobin deoxygenation in the subclavian vein. At peak exercise, arm VC was not significantly different than at rest. Leg Vo(2) represented approximately 84% of the whole body Vo(2) at intensities ranging from 38 to 100% of Wmax. Arm Vo(2) contributed between 7 and 10% to the whole body Vo(2). From 20 to 100% of Wmax, the trunk Vo(2) (including the gluteus muscles) represented between 14 and 15% of the whole body Vo(2). In summary, vasoconstrictor signals efficiently oppose the vasodilatory metabolites in the arms, suggesting that during whole body exercise in the upright position blood flow is differentially regulated in the upper and lower extremities.

In humans, arm exercise is known to elicit larger increases in arterial blood pressure (BP) than leg exercise. However, the precise regulation of regional vascular conductances (VC) for the distribution of cardiac output with exercise intensity remains unknown. Hemodynamic responses were assessed during incremental upright arm cranking (AC) and leg pedalling (LP) to exhaustion (W max ) in nine males. Systemic VC, peak cardiac output (Q peak ) (indocyanine green) and stroke volume (SV) were 18%, 23%, and 20% lower during AC than LP. The mean BP, the rate-pressure product and the associated myocardial oxygen demand were 22%, 12%, and 14% higher, respectively, during maximal AC than LP. Trunk VC was reduced to similar values at W max . At W max , muscle mass-normalized VC and fractional O 2 extraction were lower in the arm than the leg muscles. However, this was compensated for during AC by raising perfusion pressure to increase O 2 delivery, allowing a similar peak VO 2 per kg of muscle mass in both extremities. In summary, despite a lower Q peak during arm cranking the cardiovascular strain is much higher than during leg pedalling. The adjustments of regional conductances during incremental exercise to exhaustion depend mostly on the relative intensity of exercise and are limb-specific.

OBJECTIVE -Early puberty is associated with increased risk of subsequent cardiovascular disease. Low sex hormone-binding globulin (SHBG) levels are a feature of early puberty and of conditions associated with increased cardiovascular risk. The aim of the present study was to evaluate SHBG as a predictor of glucose metabolism and metabolic risk during puberty. RESEARCH DESIGN AND METHODS -This was a cross-sectional study on 132healthy Caucasian children and adolescents evaluated by an oral glucose tolerance test, a dualenergy X-ray absorptiometry scan, direct oxygen uptake measurement during cycle ergometry, and fasting blood samples.RESULTS -SHBG levels declined with advancement of puberty in both boys (P Ͻ 0.001) and girls (P ϭ 0.019). SHBG was significantly positively associated with insulin sensitivity in boys (P Ͻ 0.001) and girls (P Ͻ 0.001). In addition, SHBG was a strong predictor of insulin sensitivity (P ϭ 0.001) and the only predictor of the disposition index (P ϭ 0.031) after adjustment for puberty, fat mass, and aerobic fitness. SHBG was significantly negatively associated with metabolic risk (P ϭ 0.032) and with hypersensitive C-reactive protein levels (P ϭ 0.030) after adjustment for relevant confounders.CONCLUSIONS -SHBG was a strong predictor of insulin sensitivity and metabolic risk during puberty. Thus, we hypothesize that SHBG integrates the marked changes in glucose metabolism and body composition that occur during the pubertal transition. Diabetes Care 32:909-914, 2009

Non-technical summary Recombinant human erythropoietin (rHuEPO) decreases circulating levels of renin and aldosterone, two hormones regulating water and salt homeostasis, but the effect of rHuEPO on renal function is unknown. This study demonstrates that rHuEPO reduces the reabsorption of water and sodium in the proximal renal tubules and, probably by activation of the tubuloglomerular feedback mechanism, also causes a fall in glomerular filtration rate. Thus, the decrease in plasma concentrations of renin and aldosterone may be secondary to increased end-proximal tubular delivery of water and sodium. In conclusion, the fall in proximal reabsorption together with a reduced filtered load and a decrease in angiotensin II and aldosterone-dependent tubular reabsorption are expected to increase the oxygen tension in the renal tissue. This may serve to down-regulate the endogenous renal synthesis of EPO in the presence of high levels of circulating rHuEPO.Abstract Recombinant human erythropoietin (rHuEPO) elevates haemoglobin concentration both by increasing red blood cell volume and by a decrease in plasma volume. This study delineates the association of rHuEPO-induced changes in blood volumes with changes in the renin-aldosterone system and renal function. Sixteen healthy males were given rHuEPO for 28 days in doses raising the haematocrit to 48.3 ± 4.1%. Renal clearance studies with urine collections (N = 8) were done at baseline and at days 4, 11, 29 and 42. Glomerular filtration rate (GFR) was measured by 51 Cr-EDTA. Renal clearance of lithium (C Li ) was used as an index of proximal tubular outflow and to assess segmental renal tubular handling of sodium and water. rHuEPO-induced increases in haematocrit occurred from day 10 onwards and was caused by both an increase in red cell volume and a fall in plasma volume. Well before that (from day 2 and throughout the treatment time), rHuEPO decreased plasma levels of renin and aldosterone (N = 8) by 21-33% (P < 0.05) and 15-36% (P < 0.05), respectively. After cessation of rHuEPO, values returned to baseline. On days 11 and 29, C Li increased (P < 0.02) indicating a significant 10-16% decrease in absolute proximal reabsorption of sodium and water (APR = GFR − C Li , P < 0.05). GFR decreased slightly, albeit significantly, on day 4 (P < 0.05). In conclusion, rHuEPO promptly, and before any changes in blood volumes and haematocrit can be detected, causes a down-regulation of the renin-aldosterone system. The results are compatible with a rHuEPO-induced reduction in proximal reabsorption rate leading to activation of the tubuloglomerular feedback mechanism and a fall in GFR. Therefore, treatment with rHuEPO may result in suppression of endogenous EPO synthesis secondary to a decrease in intrarenal oxygen consumption.