Matthew L. Kearney

Interactive effect of aging and local muscle heating on renal vasoconstriction during isometric handgrip

The purpose of the study was to determine the interactive effect of aging and forearm muscle heating on renal vascular conductance and muscle sympathetic nerve activity (MSNA) during ischemic isometric handgrip. A tube-lined, water-perfused sleeve was used to heat the forearm in 12 young (27 +/- 1 yr) and 9 older (63 +/- 1 yr) subjects. Ischemic isometric handgrip was performed before and after heating. Muscle temperature (intramuscular thermistor) was 34.3 +/- 0.2 and 38.7 +/- 0.1 degrees C during normothermia and heating, respectively. At rest, heating had no effect on renal blood velocity (Doppler ultrasound) or renal vascular conductance in either group (young, n = 12; older, n = 8). Heating compared with normothermia caused a significantly greater increase in renal vasoconstriction during exercise and postexercise muscle ischemia (PEMI) in both groups. However, the increase in renal vasoconstriction during heating was greater in the older compared with the young subjects (18 +/- 3 vs. 8 +/- 3%). During handgrip, heating elicited greater increases in MSNA responses in the older group (young, n = 12; older, n = 6), whereas no statistical difference was observed between groups during PEMI. In summary, aging augments renal vascular responses to ischemic isometric handgrip during heating of the exercising muscle. The greater renal vasoconstriction was associated with augmented MSNA in the older subjects.

Aerobic Training Improves In Vivo Cholinergic Responsiveness but Not Sensitivity of Eccrine Sweat Glands

TO THE EDITOR Aerobic training improves thermal tolerance (Armstrong and Pandolf, 1988), which is postulated to result in part from improved evaporative cooling (Taylor, 1986; Shibasaki et al., 2006). Previous observations indicate that aerobic training either lowers the internal temperature at which sweating begins (sweating threshold) or increases the slopes of the internal temperaturesweat rate (Roberts et al., 1977) or exercise intensity–sweat rate relations (Yanagimoto et al., 2002). In contrast, deconditioning or detraining, associated with bedrest, increases the sweating threshold and decreases the slope of internal temperature–sweat rate relation (Lee et al., 2002). Importantly these deconditioning-related responses can be prevented by exercising during bedrest (Shibasaki et al., 2003). These studies, although informative, do not provide mechanistic insight into whether altered sweating responses to aerobic training are mediated by a central sympathetic component or at the level of the eccrine gland. Application of cholinergic agonists directly in the dermal space without repeated injections or electric current can isolate peripheral sweating responses (Crandall et al., 2003; Morgan et al., 2006; Schlereth et al., 2006). Cross-sectional studies (comparing aerobic trained vs. untrained) using electrical current drug delivery (iontophoresis) have observed increased sweating capacity and number of activated sweat glands with aerobic training (Buono and Sjoholm, 1988; Buono et al., 1992). However, these studies provided minimal insight into whether these adaptatory responses were mediated by changes in receptor responsiveness and sensitivity, or were simply a function of subject population selected. Accordingly, we tested the hypothesis that 8 weeks of aerobic training increases in vivo cholinergic sensitivity and responsiveness of eccrine sweat glands, without altering the number of exogenous acetylcholineactivated glands. Eleven sedentary, young (age1⁄4 26±1), healthy, non-obese (BMIo 30 kg m), normotensive (o140/90 mm Hg), non-smokers participated in this institutional approved longitudinal training study that adhered to Declaration of Helsinki guidelines. Each subject provided written informed consent and received a medical history and physical exam before participating in the study. Two intradermal microdialysis membranes were placed B3 cm apart in dorsal forearm skin in a similar location preand post-training, which unlike previous studies allows for continuous monitoring of sweat glands at a prescribed agonist concentration (Morgan et al., 2006). This technique involved placing a small (200-mm outer diameter, 10-mm length) semipermeable membrane (20-kDa cutoff) intradermally at a depth of approximately 0.3–1.0 mm below the epidermis (Kellogg et al., 1999). Eight doses of acetylcholine (10 7 to 1 M acetylcholine) in a lactated Ringer’s vehicle were administered for 5 minutes at 2 ml/minutes via a microdialysis infusion pump. Sweat rate was measured via capacitance hygrometry and the number of activated sweat glands was quantified using a starch–iodine technique during infusion of 1 M acetylcholine. Cholinergic dose–response relations were determined by logistic regression modeling. Endurance training consisted of running or cycling 4 times/week for 8 weeks. Subjects wore a heart rate monitor during all exercise sessions to ensure maintenance of target heart rates. Training began with exercising for 20 minutes at a work rate sufficient to achieve 80% of maximum heart rate. Exercise times increased to 60 minutes as training progressed, and high-intensity interval exercises were added twice/week during the second week to further stimulate training adaptations. Peak oxygen uptake increased from 32.9 to 40.7 ml kg 1 min 1 or 19±2% (Po0.05) and resting heart rate decreased 9±2 b.p.m. (Po0.05) indicative of a training effect. The number of cholinergic-activated glands was unchanged by training (pre-training1⁄4 40±6 and post-training1⁄4 39±7 glands per 0.5 cm). This indicates that a similar number of glands were recruited both preand post-training and that this type and duration of training does not increase the number of exogenous cholinergic-activated glands. Dose–response relations were established with goodness of fit (R) relations of 0.67±0.02 for pre-training and 0.72±0.02 for post-training, indicating that the logistic regression modeling adequately modeled the data (Figure 1). Training did not affect the ED50, but increased the maximal responses of the dose–response relation (Figure 2). These findings provide important insight into the adaptatory mechanism(s) of eccrine sweat glands to longitudinal aerobic training in humans. First, we did not observe a leftward shift in the ED50 of the cholinergic dose–response curve, strongly suggesting that exercise training does not alter eccrine sweat gland in vivo cholinergic sensitivity as previously suggested (Roberts et al., 1977; Buono et al., 1992). However, these reports suggesting an increase in cholinergic sensitivity used an iontophoresis drug delivery system to engage muscarinic receptors with pilocarpine or observed an increase in the slope of internal temperature–sweat rate relation. Pilocarpine LETTERS TO THE EDITOR