Craig G. Crandall

Cutaneous Active Vasodilation in Humans Is Mediated by Cholinergic Nerve Cotransmission

During heat stress, increases in blood flow in nonglabrous skin in humans are mediated through active vasodilation by an unknown neurotransmitter mechanism. To investigate this mechanism, a three-part study was performed to determine the following: (1) Is muscarinic receptor activation necessary for active cutaneous vasodilation? We iontophoretically applied atropine to a small area of forearm skin. At that site and an untreated control site, we measured the vasomotor (laser-Doppler blood flow [LDF]) and sudomotor (relative humidity) responses to whole-body heat stress. Blood pressure was monitored. Cutaneous vascular conductance (CVC) was calculated (LDF divided by mean arterial pressure). Sweating was blocked at treated sites only. CVC rose at both sites (P < .05 at each site); thus, cutaneous active vasodilation is not effected through muscarinic receptors. (2) Are nonmuscarinic cholinergic receptors present on cutaneous arterioles? Acetylcholine (ACh) was iontophoretically applied to forearm skin at sites pretreated by atropine iontophoresis and at untreated sites. ACh increased CVC at untreated sites (P < .05) but not at atropinized sites. Thus, the only functional cholinergic receptors on cutaneous vessels are muscarinic. (3) Does cutaneous active vasodilation involve cholinergic nerve cotransmission? Botulinum toxin was injected intradermally in the forearm to block release of ACh and any coreleased neurotransmitters. Heat stress was performed as in part 1 of the study. At treated sites, CVC and relative humidity remained at baseline levels during heat stress (P > .05). Active vasodilator and sudomotor responses to heat stress were abolished by botulinum toxin. We conclude that cholinergic nerve activation mediates cutaneous active vasodilation through release of an unknown cotransmitter, not through ACh.

Evaluation of the Cosmed K2 portable telemetric oxygen uptake analyzer.

The purpose of this study was to determine the validity and evaluate the accuracy of a portable telemetric oxygen uptake analyzer (K2). Two experiments were carried out: a) using a mechanical lung, the accuracy of the K2 to measure oxygen fractions and minute ventilation following 10 and 60 min of warm-up was determined; and b) two maximal graded exercise tests (GXT) on 15 subjects, one with the K2 system and the other with a standardized breath-by-breath (BBB) system, while heart rate (HR), minute ventilation (VE), and oxygen uptake (VO2) were compared. Following 10-min warm-up prior to calibration, the K2 underestimated the true oxygen fraction as early as 5 min into the test, and this value continued to decrease throughout the 30-min test. After 60 min of warm-up prior to calibration, the K2 accurately measured the true oxygen fraction for the first 15 min; at minute 20, and on to minute 30, the K2 underestimated the oxygen fraction. Ventilation volumes were not affected by warm-up time. Minute ventilation during the K2 GXT was significantly higher than VE for the BBB test. No significant differences were found between the HRs obtained with the BBB or K2 systems. No differences in VO2 for any stage of the GXT were identified between the K2 device, BBB device or when a respiratory exchange ratio (RER) correction factor was applied to the K2 derived values. However, the RER correction factor did minimize the VO2 differences between the BBB and K2 systems. Therefore, we conclude that the K2 accurately measures VO2 during a GXT; however, its accuracy can be compromised by limitations inherent to the system.

Blood pressure responses to dynamic exercise with lower-body positive pressure

Cardiovascular responses were obtained during cycling with graded levels of lower-body positive pressure (LBPP) applied to the exercising limbs. Seven men performed four incremental work rate (25 W.min-1) exercise (IWREx) tests to their limit of tolerance while exposed to 0, 15, 30, or 45 Torr LBPP. They also performed four, 6-min constant work rate exercise (CWREx) bouts at two work rates with LBPPs of 0 and 45 Torr. Cardiovascular data were obtained at rest and at 40%, 55%, 75%, and 90% of VO2peak, as well as at minute 5 of CWREx. LBPP did not alter VO2, HR, SV, or cardiac output (Qc) responses at rest or during exercise. However, both 30 and 45 Torr LBPP produced increases in MAP at rest and during exercise (P < 0.05). During CWREx, elevations in blood pressure were mediated via increases in TPR (P < 0.05). Only 45 Torr LBPP elicited a significantly greater blood pressure increase during exercise than rest, suggesting muscle blood flow restriction at this level of LBPP was sufficient to activate a muscle metabo-reflex. These findings suggest that the muscle metabo-reflex is not tonically active during dynamic exercise under normal conditions, but may instead require a critical reduction in muscle blood flow before it is activated.

A diminished aortic-cardiac reflex during hypotension in aerobically fit young men

We compared the aortic-cardiac baroreflex sensitivity in eight average fit (AF: VO2max = 44.7 +/- 1.3 ml.kg-1 x min-1) and seven high fit (HF: VO2max = 64.1 +/- 1.7 ml.min-1 x kg-1) healthy young men during hypotension elicited by steady state sodium nitroprusside (SN) infusion. During SN mean arterial pressure (MAP) was similarly decreased in AF (-12.6 +/- 1.0 mm Hg) and HF (-12.1 +/- 1.1 mm Hg). However, the increases in heart rate (HR) were less (P < 0.023) in HF (15 +/- 3 bpm) than AF (25 +/- 1 bpm). When sustained neck suction (NS, -22 +/- 1 torr in AF and -20 +/- 1 torr in HF, P > 0.05) was applied to counteract the decreased carotid sinus transmural pressure during SN, thereby isolating the aortic baroreceptors, the increased HR remained less (P < 0.021) in HF (8 +/- 2 bpm) than AF (16 +/- 2 bpm). During both SN infusion and SN+NS, the calculated gains (i.e., delta HR/delta MAP) were significantly greater in AF (2.1 +/- 0.3 and 1.3 +/- 0.2 bpm.mm Hg-1) than HF (1.2 +/- 0.2 and 0.6 +/- 0.2 bpm.mm Hg-1). However, the estimated carotid-cardiac baroreflex sensitivity (i.e., the gain difference between the stage SN and SN + NS) was not different between AF (0.7 +/- 0.2 bpm.mm Hg-1) and HF (0.6 +/- 0.1 bpm.mm Hg-1). These data indicated that the aortic-cardiac baroreflex sensitivity during hypotension was significantly diminished with endurance exercise training.

Aerobic fitness: I. Response of volume regulating hormones to head-down tilt

We investigated the relationship of aerobic fitness to the response of volume-regulating hormones to acute simulated microgravity. Six untrained (UT) and six endurance-trained (ET) healthy young males were studied in the head-down tilt (HDT) position of -6 degrees for 4 h. Peak oxygen uptake (VO2peak) and plasma volume (PV) were significantly greater in the ET (VO2peak = 61.7 +/- 1.6 ml.min-1.kg-1 and PV = 53.1 +/- 2.8 ml.kg-1) than in the UT (VO2peak = 38.4 +/- 1.7 ml.min-1.kg-1 and PV = 38.8 +/- 1.0 ml.kg-1). Plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), norepinephrine (NE), renin activity (PRA), and aldosterone (PA) were measured prior to HDT and at minutes 2, 5, 15, 30, 60, 120, 180, and 240 during HDT. PRA and PA significantly decreased during the time of HDT in both groups. The changes in ANP and NE concentrations were not significantly different between the groups nor across time. However, in the ET subjects, the changes in PRA and NE were significantly correlated with the changes in ANP (r = 0.49, P less than 0.01; and r = 0.86, P less than 0.001, respectively); in the UT subjects, the changes in AVP, PRA, and PA were significantly associated with changes in NE (r = 0.34, P less than 0.03; and r = 0.59; and r = 0.53, P less than 0.01, respectively). PV significantly decreased during HDT, and was primarily related to the decrease in PA in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerobic fitness. II: Orthostasis and VO2peak following head-down tilt

To determine whether endurance exercise trained (ET) subjects would experience greater reductions in peak oxygen delivery and orthostatic tolerance (OT) than untrained (UT) subjects, both peak oxygen uptake (VO2peak) during upright bicycle ergometry and tolerance time during 70 degrees head-up tilt (HUT) were compared within and between groups before and after 4 h of -6 degrees head-down tilt (HDT). Eight ET subjects with a mean VO2peak of 61.7 +/- 1.6 ml.kg-1.min-1 were matched for age, height, and weight with eight UT subjects (VO2peak = 38.4 +/- 1.7 ml.kg-1.min-1). Following HDT, decreases in plasma volume (PV) were larger for ET subjects (-3.7 +/- 0.5 ml.kg-1) than for UT subjects (-2.3 +/- 0.3 ml.kg-1), P less than 0.03. Reductions in VO2peak for ET subjects (-5.4 +/- 1.1 ml.kg-1.min-1) were also greater than for UT subjects (-2.4 +/- 0.8 ml.kg-1.min-1), P less than 0.05. The ET (N = 6) subjects also had a significant decrease in OT time (-13.0 +/- 4.2 min) during post-HDT HUT, which was not observed for the UT group (N = 6). A significant inverse correlation was found pre-HDT VO2peak and the change in OT time, r = -0.74, P less than 0.01. The decrease in OT was also significantly correlated to the PV decrease, r = 0.59, P less than 0.04. The UT subjects had significantly augmented pressor responses to HUT manifested by the increases in both HR and MAP following HDT.(ABSTRACT TRUNCATED AT 250 WORDS)