Human skeletal muscle sympathetic nerve activity, heart rate and limb haemodynamics with reduced blood oxygenation and exercise.
ABSTRACT Acute systemic hypoxia causes significant increases in human skeletal muscle sympathetic nerve activity (MSNA), heart rate and ventilation. This phenomenon is thought to be primarily mediated by excitation of peripheral chemoreceptors sensing a fall in arterial free oxygen partial pressure (Pa,O2). We directly tested the role of Pa,O2 on MSNA (peroneal microneurography), heart rate, ventilation and leg haemodynamics (n = 7-8) at rest and during rhythmic handgrip exercise by using carbon monoxide (CO) to mimic the effect of systemic hypoxia on arterial oxyhaemoglobin (approximately 20 % lower O2Hba), while normalising or increasing Pa,O2 (range 40-620 mmHg). The four experimental conditions were: (1) normoxia (Pa,O2 approximately 110 mmHg; carboxyhaemoglobin (COHb) approximately 2 %); (2) hypoxia (Pa,O2 approximately 40 mmHg; COHb approximately 2 %); (3) CO + normoxia (Pa,O2 approximately 110 mmHg; COHb approximately 23 %); and (4) CO + hyperoxia (Pa,O2 approximately 620 mmHg; COHb ~24 %). Acute hypoxia augmented sympathetic burst frequency, integrated MSNA, heart rate and ventilation compared to normoxia over the entire protocol (7-13 bursts min-1, 100-118 %, 13-17 beats min-1, 2-4 l min-1, respectively, P < 0.05). The major new findings were: (1) CO + normoxia and CO + hyperoxia also elevated MSNA compared to normoxia (63-144 % increase in integrated MSNA; P < 0.05) but they did not increase heart rate (62-67 beats min-1) or ventilation (6.5-6.8 l min-1), and (2) despite the 4-fold elevation in MSNA with hypoxaemia and exercise, resting leg blood flow, vascular conductance and O2 uptake remained unchanged. In conclusion, the present results suggest that increases in MSNA with CO are not mediated by activation of the chemoreflex, whereas hypoxia-induced tachycardia and hyperventilation are mediated by activation of the chemoreflex in response to the decline in Pa,O2. Our findings also suggest that Pa,O2 is not an obligatory signal involved in the enhanced MSNA with reduced blood oxygenation.
Article: Effect of acute hypoxia on vascular responsiveness in man. I. Responsiveness to lower body negative pressure and ice on the forehead. II. Responses to norepinephrine and angiotensin. 3. Effect of hypoxia and hypocapnia.[show abstract] [hide abstract]
ABSTRACT: An effect of hypoxemia on vascular responsiveness and blood pressure regulation has not been demonstrated in man. The response of forearm resistance vessels to several vasoconstrictor stimuli was compared during normoxia and acute hypoxia. Forearm vasoconstrictor responses to lower body negative pressure and to the application of ice to the forehead, which are neurogenic stimuli, were decreased during acute hypoxia. Lower body negative pressure caused a decrease in mean arterial pressure during hypoxia, but not during normoxia. Because norepinephrine is the neurotransmitter released during reflex vasoconstriction, we considered the possibility that decreased responsiveness to norepinephrine might be one mechanism for diminished responses to lower body negative pressure and ice on the forehead during hypoxia. Hypoxia decreased the response of forearm resistance vessels to infusions of norepinephrine and angiotensin into the brachial artery. In addition, the effectiveness of intravenous infusions of norepinephrine in elevating mean arterial pressure was decreased during hypoxia. Since exposure to acute hypoxia stimulates hyperventilation and hypocapnia, experiments were done to determine the contribution of hypocapnia during hypoxia to the decreased vasoconstriction. The results indicate that hypocapnia may diminish the vascular response to some stimuli, but the reduction in oxygen appears to be the primary mechanism for decreased vasoconstrictor responses during acute hypoxia.Journal of Clinical Investigation 07/1970; 49(6):1252-65. · 15.39 Impact Factor
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ABSTRACT: A three-part experiment was designed to show whether hypoxemia alters splanchnic vasomotor responses to other stresses by vasodilating splanchnic organs, preventing norepinephrine (NE)-induced vasoconstriction, or altering total sympathetic nervous activity (SNA) assessed by plasma levels of NE and epinephrine (Epi). Splanchnic blood flow (SBF) was measured by plasma clearance and hepatic extraction of indocyanine green (constant infusion). Part I: two degrees of hypoxemia [fractional concn of inspired O2 (FIO2) = 10.4 and 7.6%, arterial PO2 (PaO2) = 34.8 and 27 Torr] caused a small splanchnic vasodilation; resistance fell 16 and 26%, respectively, in five men; and SBF rose from 1.78 to 2.04 (10.4% O2) and to 2.02 1 X min-1 (7.6% O2). Plasma NE was unaffected by hypoxemia and by a fall in mean arterial pressure from 82 to 63 Torr at FIO2 = 7.6%. Part II: NE infused intravenously to raise pressure by 20 Torr in five subjects breathing air and 10.3% O2 caused splanchnic vasoconstriction irrespective of PaO2. Part III: in six subjects, two levels of hypoxemia (FIO2 = 10.4 and 7.7%) did not increase NE levels in five men, and Epi increased in two men only at FIO2 = 7.7%. We conclude that hypoxemia caused only a small splanchnic vasodilation not mediated by Epi, did not prevent transient NE-induced vasoconstriction, and either did not significantly increase SNA or prejunctionally inhibited NE release. Severe hypoxemia abolished the rise in NE and heart rate in response to falling pressure.The American journal of physiology 10/1986; 251(3 Pt 2):H562-70.
Article: The contributions of former presidents of the section of proctology to the problem of carcinoma of the rectum.Proceedings of the Royal Society of Medicine 02/1959; 52(Suppl):32-3.