Comparison of hemodynamic and sympathoneural responses to adenosine and lower body negative pressure in man

Abstract

Adenosine increases heart rate and sympathetic nerve activity reflexively in conscious humans through several mechanisms. The purpose of this study was to assess the relative contributions of arterial baroreceptor unloading, carotid chemoreceptor stimulation, and other adenosine-sensitive afferent nerves to these responses. In 12 healthy men, the effect on blood pressure, heart rate (HR), and muscle sympathetic nerve activity (MSNA; peroneal nerve) of lower body negative pressure (LBNP; -15 mmHg (1 mmHg =133.3 Pa)) was compared with the effect of intravenous adenosine (35, 70, and 140 |ag*kg"1*min_1). In eight subjects, the highest dose was reinfused during 100% oxygen to suppress arterial chemoreceptors. Blood pressure reductions during LBNP and adenosine (140 jxg-kg'^min"1) were similar. HR did not change significantly during LBNP (+2 ± 2 beats/min; mean ± SE) but increased at the highest adenosine dose (+25 ± 3 beats/min; p < 0.05). MSNA increased significantly (p < 0.05) during both interventions (+255 ± 82 and +247 ± 5 8 units/100 beats for adenosine and LBNP, respectively), and there was no difference in the MSNA response to these two stimuli (p > 0.1). Oxygen inhibited adenosine-induced increases in HR and MSNA (from +305 ± 99 to +198 ± 75 units/100 beats and from +26 ± 4 to +18 ± 3 beats/min;p < 0.05 for both comparisons). The MSNA response to these combined stimuli was similar to that observed during LBNP. In contrast, the residual HR response (+18 ± 3 beats/min) was significantly greater than the response to LBNP (+2 ± 2 beats/min; p < 0.05). These data indicate that arterial baroreceptor unloading cannot account for the marked adenosine-induced increase in HR, but may be sufficient to explain its effect on MSNA. The effect of 100% oxygen confirms that stimulation of carotid chemoreceptors accounts for approximately one-third of the HR and MSNA response to adenosine. However, other mechanisms, such as stimulation of adenosine-sensitive afferent nerves in other vascular beds, are involved in the HR and possibly the MSNA response.Key words: adenosine, human, heart rate, sympathetic nervous system, baroreflex.Résumé : L 'adénosine augmente la fréquence cardiaque et l'activité nerveuse sympathique de manière réflexe chez les humains conscients et ce, par 1*intermédiaire de divers mécanismes. Le but de la présente étude a été d'évaluer l'influence sur ces réponses d'une décharge des barorécepteurs artériels, d'une stimulation des chémorécepteurs carotidiens, ainsi que d'autres nerfs afférents sensibles à Padénosine. Chez 12 hommes sains, on a comparé l'effet d 'une pression négative des membres inférieurs (PNMI; -15 mmHg (1 mmHg = 133,3 Pa)) avec celui de Padénosine intraveineuse (35, 70 et 140 jig-kg^-m ür1) sur la pression artérielle, la fréquence cardiaque (FC) et l'activité nerveuse sympathique musculaire (ANSM; nerf périonnier). Chez huit sujets, on a réinjecté la plus forte dose d'adénosine en présence de 100% d'oxygène afin de supprimer les chémorécepteurs artériels. Les réductions de press...

Sustained hyperglycaemia increases muscle blood flow but does not affect sympathetic activity in resting humans

“…An isolated electrode was positioned into the peroneal nerve, guided by internal stimulation (duration 1 msec, frequency 1 Hz, voltage 3-6 V) and further adjusted to improve the signal-to-noise ratio. Both electrodes were connected to a preamplifier and the signal was transduced to the neurograph, amplified (variable, 20-99 times), filtered (band width 700-2,000 Hz) and rectified (Rongen et al 1997). Finally, the signal was integrated with a time constant of 0.1 s, displayed on the computer monitor, stored and sent to a loudspeaker.…”

Effect of adenosine on heart rate variability in humans

“…The sympathetic nervous system responds to some internal or external challenges in a highly selective and organ-specific manner, whereas, under other circumstances, such stimuli elicit a generalized sympathoexcitatory response [29][30][31]. When considered in the context of previous reports that adenosine, infused at the dose used in the present study, increases muscle sympathetic nerve activity and heart rate [3,4], these observations with respect to heart rate variability indicate that the systemic infusion of adenosine evokes a generalized reflex sympatho-excitatory response involving the heart, in addition to other vascular beds.…”

“…Several independent, yet complementary, methods have been used to characterize the reflex adrenergic response to adenosine infusion : peroneal muscle sympathetic nerve traffic [3,4], plasma noradrenaline concentration [22] and total body noradrenaline spillover [23]. However, the effect of exogenous adenosine on cardiac sympathetic neural drive, as assessed by heart rate variability, has not been described.…”

“…In conscious humans, adenosine evokes a receptorspecific sympatho-excitatory reflex by stimulating afferent nerve endings in the carotid body, skeletal muscle, heart and kidney [3][4][5][6][7][8]. Several independent, yet complementary, methods have been used to characterize the reflex adrenergic response to adenosine infusion : peroneal muscle sympathetic nerve traffic [3,4], plasma noradrenaline concentration [22] and total body noradrenaline spillover [23].…”

“…These properties are the basis for one clinical application of adenosine, namely the interruption of supraventricular tachycardia by bolus injection. However, when infused intravenously into conscious humans, to achieve lower plasma concentrations, adenosine increases both heart rate and sympathetic nerve traffic to muscle [3,4]. There are two stimuli to this activation of the sympathetic nervous system : peripheral vasodilation, which reduces baroreceptor afferent nerve discharge, and a receptor-specific sympatho-excitatory reflex elicited by stimulating afferent nerve endings in the carotid body, skeletal muscle, heart and kidney [4][5][6][7][8][9][10].…”