Biomedical subjects

John R Halliwill

Publications and source records attributed to John R Halliwill.

28 records · Page 2Linked to original sources

PubMed2004

Vasomotor responses to hypoxia in type 2 diabetes.

Type 2 diabetes is associated with vascular dysfunction, accelerated atherosclerotic morbidity, and mortality. Abnormal vasomotor responses to chemoreflex activation may contribute to the acceleration of atherosclerotic diabetes complications, but these responses have not previously been investigated. We measured forearm mean blood flow (MBF) and mean vascular conductance (MVC) responses to isocapnic hypoxia in seven healthy and eight type 2 diabetic subjects during local intra-arterial saline infusion and alpha-adrenergic blockade (phentolamine). The effects of hypoxia on saline and phentolamine responses significantly differed between groups; relative to normoxia, the %DeltaMVC with hypoxia during saline was -3.3 +/- 11.2% in control and 24.8 +/- 13.3% in diabetic subjects, whereas phentolamine increased hypoxic %DeltaMVC to similar levels (39.4 +/- 9.7% in control subjects and 48.0 +/- 11.8% in diabetic subjects, P < 0.05, two-way ANOVA). Absolute normoxic MBF responses during saline infusion were 91.9 +/- 21.1 and 77.9 +/- 15.3 in control and diabetic subjects, respectively, and phentolamine increased normoxic MBF to similar levels (165.2 +/- 40.1 ml/min in control subjects and 175.9 +/- 32.0 ml/min in diabetic subjects; both P < 0.05). These data indicate that diabetic and control subjects exhibit similar responses to hypoxia in the presence of alpha-adrenergic blockade despite evidence of exaggerated alpha-mediated vasoconstriction at rest.

Adrenergic alpha-Antagonists↗

PubMed2003

Influences of hydration on post-exercise cardiovascular control in humans.

Dehydration is known to decrease orthostatic tolerance and cause tachycardia, but little is known about the cardiovascular control mechanisms involved. To test the hypothesis that arterial baroreflex sensitivity increases during exercise-induced dehydration, we assessed arterial baroreflex responsiveness in 13 healthy subjects (protocol 1) at baseline (PRE-EX) and 1 h after (EX-DEH) 90 min of exercise to cause dehydration, and after subsequent intravenous rehydration with saline (EX-REH). Six of these subjects were studied a second time (protocol 2) with intravenous saline during exercise to prevent dehydration. We measured heart rate, central venous pressure and arterial pressure during all trials, and muscle sympathetic nerve activity (MSNA) during the post-exercise trials. Baroreflex responses were assessed using sequential boluses of nitroprusside and phenylephrine (modified Oxford technique). After exercise in protocol 1 (EX-DEH), resting blood pressure was decreased and resting heart rate was increased. Cardiac baroreflex gain, assessed as the responsiveness of heart rate or R-R interval to changes in systolic pressure, was diminished in the EX-DEH condition (9.17 +/- 1.06 ms mmHg-1 vs. PRE-EX: 18.68 +/- 2.22 ms mmHg-1, P < 0.05). Saline infusion after exercise did not alter the increase in HR post-exercise or the decrease in baroreflex gain (EX-REH: 10.20 +/- 1.43 ms mmHg-1; P > 0.10 vs. EX-DEH). Saline infusion during exercise (protocol 2) resulted in less of a post-exercise decrease in blood pressure and a smaller change in cardiac baroreflex sensitivity. Saline infusion caused a decrease in MSNA in protocol 1. We conclude that exercise-induced dehydration causes post-exercise changes in the baroreflex control of blood pressure that may contribute to, rather than offset, orthostatic intolerance.

Adult↗

PubMed2003

Peripheral chemoreflex and baroreflex interactions in cardiovascular regulation in humans.

We tested the hypothesis that activation of peripheral chemoreceptors with acute isocapnic hypoxia resets arterial baroreflex control of both heart rate and sympathetic vasoconstrictor outflow to higher pressures, resulting in increased heart rate and muscle sympathetic nerve activity without changes in baroreflex sensitivity. We further hypothesized that this resetting would not occur during isocapnic hyperpnoea at the same breathing rate and depth as during isocapnic hypoxia. In 12 healthy, non-smoking, normotensive subjects (6 women, 6 men, 19-36 years), we assessed baroreflex control of heart rate and muscle sympathetic nerve activity using the modified Oxford technique during normoxia, isocapnic hyperpnoea, and isocapnic hypoxia (85 % arterial O2 saturation). While isocapnic hyperpnoea did not alter heart rate, arterial pressure, or sympathetic outflow, hypoxia increased heart rate from 61.9 +/- 1.8 to 74.7 +/- 2.7 beats min-1 (P < 0.05), increased mean arterial pressure from 97.4 +/- 2.0 to 103.9 +/- 3.3 mmHg (P < 0.05), and increased sympathetic activity 22 +/- 13 % relative to normoxia and 72 +/- 21 % (P < 0.05) relative to hyperpnoea alone. The sensitivity for baroreflex control of both heart rate and sympathetic activity was not altered by either hypoxia or hyperpnoea. Thus, it appears that acute activation of peripheral chemoreceptors with isocapnic hypoxia resets baroreflex control of both heart rate and sympathetic activity to higher pressures without changes in baroreflex sensitivity. Furthermore, these effects appear largely independent of breathing rate and tidal volume.

Adult↗

PubMed2003

Alpha-adrenergic vascular responsiveness during postexercise hypotension in humans.

In sedentary individuals, postexercise hypotension following a single bout of aerobic exercise is due to an unexplained peripheral vasodilatation. We tested the hypothesis that alpha-adrenergic responsiveness in the forearm and leg vasculatures is blunted during postexercise hypotension. We studied 12 men and two women before and 30 min after a 60 min bout of cycling at 60 % VO2,peak. In the first five subjects, arterial pressure (brachial artery catheter) and forearm blood flow (plethysmography) were measured and vascular conductance was calculated during intraarterial infusions of the alpha1-agonist phenylephrine and the alpha2-agonist clonidine. Exercise reduced mean arterial pressure (89 +/- 2 vs. 95 +/- 2 mmHg, P < 0.05) and increased forearm vascular conductance 77 +/- 33 % (P < 0.05). Despite these changes in baseline vascular conductance, vasoconstrictor responses in the forearm to phenylephrine and clonidine were similar (or enhanced) postexercise vs. preexercise. In the remaining nine subjects, arterial pressure (femoral artery catheter) and leg blood flow (Doppler ultrasound of the femoral artery) were measured and vascular conductance was calculated during intraarterial infusions of phenylephrine and clonidine. Exercise reduced mean arterial pressure (80 +/- 2 vs. 89 +/- 2 mmHg, P < 0.05) and increased leg vascular conductance 94 +/- 16 % (P < 0.05). Despite these changes in baseline vascular conductance, vasoconstrictor responses in the leg to phenylephrine and clonidine were similar (or enhanced) postexercise vs. preexercise. These results suggest that vascular responsiveness to alpha-adrenergic agonists is maintained during postexercise hypotension in humans. Thus, while postexercise hypotension is associated with increased vascular conductance in the forearm and leg, it does not appear that blunting of alpha-adrenergic responsiveness is the cause.

Adrenergic alpha-Agonists↗

PubMed2003

Failure of systemic hypoxia to blunt alpha-adrenergic vasoconstriction in the human forearm.

Systemic hypoxia in humans evokes forearm vasodilatation despite significant reflex increases in sympathetic vasoconstrictor nerve activity and noradrenaline spillover. We sought to determine whether post-junctional alpha-adrenergic vasoconstrictor responsiveness to endogenous noradrenaline release is blunted during systemic hypoxia. To do so, we conducted a two-part study in healthy young adults. In protocol 1, we measured forearm blood flow (FBF; venous occlusion plethysmography) and calculated the vascular conductance (FVC) responses to brachial artery infusions of two doses of tyramine (evokes endogenous noradrenaline release) in 10 adults during normoxia and mild systemic hypoxia (85 % O2 saturation; pulse oximetry of the earlobe). Systemic hypoxia evoked significant forearm vasodilatation as indicated by the increases in FBF and FVC (approximately 20-23 %; P < 0.05). The low and high doses of tyramine evoked significant reductions in FVC (vasoconstriction) that were similar in magnitude during normoxia (-29 +/- 3 and -53 +/- 4 %) and mild hypoxia (-35 +/- 4 and -58 +/- 3 %; P = 0.33). In protocol 2, forearm vasoconstrictor responses to the high dose of tyramine were determined in eight young adults during normoxia and during graded levels of systemic hypoxia (85, 80 and 75 % O2 saturation). The reductions in FVC were similar during normoxia (-59 +/- 2 %) and the three levels of hypoxia (85 % O2 saturation, -64 +/- 3 %; 80 % O2 saturation, -62 +/- 1 %; 75 % O2 saturation, -61 +/- 3 %; P = 0.37). In both protocols, the tyramine-induced increases in deep venous noradrenaline concentrations were similar during normoxia and all levels of hypoxia. Our results demonstrate that post-junctional alpha-adrenergic receptor vasoconstrictor responsiveness to endogenous noradrenaline release is not blunted during mild-to-moderate systemic hypoxia in healthy humans.

Adult↗

PubMed2003

Cardiovascular and autonomic responses to lower body negative pressure: do not explain gender differences in orthostatic tolerance.

This study tested the hypotheses that differences in the adrenergic, central venous pressure (CVP), cardiovascular, or baroreflex responses to lower body negative pressure (LBNP) or differences in body size would be associated with gender differences in orthostatic tolerance. Subjects (24 females, 22 males) underwent graded LBNP to -100 mmHg or presyncope. At rest, the males had higher SV (+ 21 ml x beat(-1)), cardiac output (+ 1.65 L x min(-1)), systolic blood pressure (+ 29 mmHg) and mean arterial pressure (+ 8 mmHg; all P < 0.05). Neither the CVP responses to LBNP to -60 mmHg, the deltaforearm vascular conductance/deltaCVP with LBNP to -20 mmHg nor the deltaheart rate/deltaCVP with LBNP of -30 to -60 mmHg differed between genders. LBNP tolerance was lower for the females than males (276 +/- 12 vs 337 +/- 14 mmHg x min; LBNP tolerance index; P < 0.01) and, of the resting data, only gender was associated with LBNP tolerance (R(2) = 20 %). Use of gender, the maximal change in HR with LBNP and the change in HR from 0 to -40 mmHg in a regression equation could explain 75 % of the variability in orthostatic tolerance. No cardiovascular parameter differed between genders in the two minutes preceding presyncope. In the last completed stage and at test termination, [epinephrine] and [norepinephrine] were higher in the men. These data suggest that the CVP, cardiovascular and baroreflex responses to graded LBNP are similar in men and women despite marked differences in LBNP tolerance. Differences in body size do not explain the gender difference although differences in the adrenergic responses at maximal LBNP may play a role.

Adult↗

PubMed2003

Hypoxic regulation of blood flow in humans. Skeletal muscle circulation and the role of epinephrine.

Vascular tone represents the balance between local vasodilator mechanisms which attempt to secure adequate blood flow for metabolic demand and neural vasoconstrictor reflexes attempting to maintain arterial pressure. Hypoxia alters vascular tone, shifting this balance in complex ways. Hypoxic vascular responses are not uniform across vascular beds and the mechanisms of hypoxic vasodilation appear to be tissue specific. In healthy humans, skeletal muscle vascular beds exhibit a graded vasodilation in response to hypoxia despite increases in sympathetic vasoconstrictor nerve activity. Previous studies have documented a number of vasodilator substances or systems that appear to be involved in this hypoxic vasodilation. My colleagues and I have conducted studies on the extent to which sympathetic vasoconstriction can mask hypoxic vasodilation, and how sympathetic vasoconstrictor activity interacts with local factors that mediate hypoxic vasodilation in humans. We have focused largely on beta-adrenergic mediated vasodilation, noting that it produces some of its effects via a nitric oxide (NO) pathway. This review will explore the role of epinephrine in generating skeletal muscle vasodilation. How the many factors that determine vascular tone during hypoxic stress impact on the regulation of arterial pressure and how hypoxic vasodilation is altered in several pathophysiological conditions will be discussed.

Altitude Sickness↗

PubMed2002

Orthostatic intolerance after space flight.

Physiologists have always been challenged by the adjustments of the human body to hostile environments. The set of papers in this issue of The Journal of Physiology (Cox et al. 2002; Ertl et al. 2002; Levine et al. 2002) fits into the tradition of the study of human responses to extreme physical circumstances. The Neurolab project represents a huge undertaking that required major contributions from many different collaborators, and the coordination of efforts at different institutions. The studies succeeded because of the dedication and years of work of the astronauts involved. The manuscripts present the fundamental findings from the first direct recordings of sympathetic vasoconstrictor nerves and noradrenaline kinetics in humans during microgravity. Despite the difficulties of performing such measurements on the space shuttle and the small numbers of astronauts involved, unique data are set forth that represent a major advance in our understanding of the physiology of space flight.

Adaptation, Physiological↗

PubMed2002

Influence of endurance exercise training status and gender on postexercise hypotension.

In sedentary individuals, postexercise hypotension after a single bout of aerobic exercise is due to a peripheral vasodilation. Endurance exercise training has the potential to modify this response and perhaps reduce the degree of postexercise hypotension. We tested the hypothesis that endurance exercise-trained men and women would have blunted postexercise hypotension compared with sedentary subjects but that the mechanism of hypotension would be similar (i.e., vasodilation). We studied 16 endurance-trained and 16 sedentary men and women. Arterial pressure, cardiac output, and total peripheral resistance were determined before and after a single 60-min bout of exercise at 60% peak oxygen consumption. All groups exhibited a similar degree of postexercise hypotension (approximately 4-5 mmHg; P < 0.05 vs. preexercise). In sedentary men and women, hypotension was the result of vasodilation (Deltaresistance: -8.9 +/- 2.2%). In endurance-trained women, hypotension was also the result of vasodilation (-8.1 +/- 4.1%). However, in endurance-trained men, hypotension was the result of a reduced cardiac output (-5.2 +/- 2.4%; P < 0.05 vs. all others) and vasodilation was absent (-0.7 +/- 3.3%; P < 0.05 vs. all others). Thus we conclude the magnitude of postexercise hypotension is similar in sedentary and endurance-trained men and women but that endurance-trained men and women achieve this fall in pressure via different mechanisms.

Adult↗

PubMed2002

Effect of hypoxia on arterial baroreflex control of heart rate and muscle sympathetic nerve activity in humans.

We tested the hypothesis that acute hypoxia would alter the sensitivity of arterial baroreflex control of both heart rate and sympathetic vasoconstrictor outflow. In 16 healthy, nonsmoking, normotensive subjects (8 women, 8 men, age 20-33 yr), we assessed baroreflex control of heart rate and muscle sympathetic nerve activity by using the modified Oxford technique during both normoxia and hypoxia (12% O(2)). Compared with normoxia, hypoxia reduced arterial O(2) saturation levels from 96.8 +/- 0.3 to 80.7 +/- 1.4% (P < 0.001), increased heart rate from 59.8 +/- 2.4 to 79.4 +/- 2.9 beats/min (P < 0.001), increased mean arterial pressure from 96.7 +/- 2.5 to 105.0 +/- 3.3 mmHg (P = 0.002), and increased sympathetic activity 126 +/- 58% (P < 0.05). The sensitivity for baroreflex control of both heart rate and sympathetic activity was not altered by hypoxia (heart rate: -1.02 +/- 0.09 vs. -1.02 +/- 0.11 beats. min(-1). mmHg(-1); nerve activity: -5.6 +/- 0.9 vs. -6.2 +/- 0.9 integrated activity. beat(-1). mmHg(-1); both P > 0.05). Acute exposure to hypoxia reset baroreflex control of both heart rate and sympathetic activity to higher pressures without changes in baroreflex sensitivity.

Adult↗