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Biomedical subjects

A L Mark

Publications and source records attributed to A L Mark.

At least 55 records · Page 3Linked to original sources
PubMed1994

Effects of fludrocortisone on sympathetic nerve activity in humans.

Fludrocortisone reduces plasma norepinephrine in healthy humans, but forearm vascular and pressor responses to norepinephrine are potentiated. The effects of fludrocortisone on sympathetic nerve activity in healthy humans are not known. To investigate these effects we evaluated muscle sympathetic nerve activity, heart rate, and arterial pressure in 11 healthy volunteers during three protocols: (1) before and on day 7 of fludrocortisone (0.4 mg/d) treatment with ad libitum diet (n = 6); (2) before and on day 7 of fludrocortisone (0.4 mg/d) or placebo with a 150 mmol/24 h (mEq/24 h) sodium diet (n = 7); and (3) before and on day 2 of fludrocortisone (0.4 mg/d) or placebo with a 150 mmol/24 h (mEq/24 h) sodium diet (n = 4). Placebo did not alter any parameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Anteroventral third ventricle lesions abolish lumbar sympathetic responses to insulin.

Insulin has been shown to increase sympathetic nerve activity. Because evidence shows that insulin acts within the central nervous system, we hypothesized that lesions of the anteroventral third ventricle region, an area rich in insulin receptors, would abolish sympathetic responses to hyperinsulinemia. We measured mean arterial pressure and lumbar sympathetic nerve activity in fasted, anesthetized sham-lesioned (n = 8) and lesioned (n = 8) rats before and after intravenous insulin infusion at 0.13 U/h during euglycemic clamp. Additional sham-lesioned (n = 10) and lesioned (n = 5) rats received vehicle infusion. Insulin-infused sham-lesioned rats had substantially greater increases in lumbar sympathetic nerve activity (+83 +/- 18%) than vehicle-infused sham-lesioned rats (+27 +/- 4%). Most importantly, insulin-infused lesioned rats had increases in sympathetic activity (+32 +/- 11%) that were no greater than lesioned rats receiving vehicle (+23 +/- 16%). Blood pressure was not altered by insulin or vehicle. To test the possibility that lesions of the anteroventral third ventricle region nonspecifically suppress sympathetic excitatory responses, we evaluated reflex increases in lumbar sympathetic activity to nitroglycerin in sham-lesioned (n = 5) and lesioned (n = 8) rats. Rats with lesions and sham lesions showed comparable increases in lumbar nerve activity during nitroglycerin-induced hypotension. In summary, increases in sympathetic nerve activity to intravenous insulin infusion are abolished by anteroventral third ventricle lesions. These data indicate that the integrity of this brain region is necessary for activation of lumbar sympathetic nerve activity by systemic administration of insulin.

Animals↗
PubMed1993

Sympathetic-nerve activity during sleep in normal subjects.

BACKGROUND: The early hours of the morning after awakening are associated with an increased frequency of events such as myocardial infarction and ischemic stroke. The triggering mechanisms for these events are not clear. We investigated whether autonomic changes occurring during sleep, particularly rapid-eye-movement (REM) sleep, contribute to the initiation of such events. METHODS: We measured blood pressure, heart rate, and sympathetic-nerve activity (using microneurography, which provides direct measurements of efferent sympathetic-nerve activity related to muscle blood vessels) in eight normal subjects while they were awake and while in the five stages of sleep. RESULTS: The mean (+/- SE) amplitude of bursts of sympathetic-nerve activity and levels of blood pressure and heart rate declined significantly (P < 0.001), from 100 +/- 9 percent, 90 +/- 4 mm Hg, and 64 +/- 2 beats per minute, respectively, during wakefulness to 41 +/- 9 percent, 80 +/- 4 mm Hg, and 59 +/- 2 beats per minute, respectively, during stage 4 of non-REM sleep. Arousal stimuli during stage 2 sleep elicited high-amplitude deflections on the electroencephalogram (called K complexes), which were frequently associated with bursts of sympathetic-nerve activity and transient increases in blood pressure. During REM sleep, sympathetic-nerve activity increased significantly (to 215 +/- 11 percent; P < 0.001) and the blood pressure and heart rate returned to levels similar to those during wakefulness. Momentary restorations of muscle tone during REM sleep (REM twitches) were associated with cessation of sympathetic-nerve discharge and surges in blood pressure. CONCLUSIONS: REM sleep is associated with profound sympathetic activation in normal subjects, possibly linked to changes in muscle tone. The hemodynamic and sympathetic changes during REM sleep could play a part in triggering ischemic events in patients with vascular disease.

Adult↗
PubMed1993

Sympathetic neural mechanisms in human hypertension.

This review discusses the role of the sympathetic nervous system in the pathogenesis and maintenance of human hypertension. Three points are emphasized: first, there are mechanisms by which the sympathetic nervous system can contribute to the long-term regulation of vascular resistance and arterial pressure in addition to the moment-to-moment regulation of arterial pressure; second, the microneurographic method for direct intraneural recording of sympathetic nerve activity in humans has provided mounting evidence for increased sympathetic neural activity in human essential and renovascular hypertension; and third, there are both peripheral reflex and humoral mechanisms that may contribute to sympathetic overactivity in human hypertension.

Humans↗
PubMed1993

Muscle sympathetic nerve responses to dynamic one-legged exercise: effect of body posture.

Previous studies examining muscle sympathetic nerve activity (MSNA) during dynamic exercise have focused on upper extremity exercise. The present study was undertaken to investigate 1) MSNA responses to dynamic one-legged knee extensions (DLE) and 2) the role of the cardiopulmonary baroreflexes in the modulation of MSNA responses to DLE. MSNA was measured during 4 min of DLE at 20 (n = 10) and 30 W (n = 9) and during 3 min of DLE at 40 W (n = 9). DLE was performed in the upright (sitting) position and MSNA was recorded in the contralateral leg (peroneal nerve). DLE elicited significant increases in mean arterial pressure (MAP) and heart rate (HR; P < 0.05). In contrast to previous studies using dynamic arm exercise, MSNA (bursts/min) decreased by 25% (P < 0.05) during the first minute of DLE from resting control and remained suppressed during the remaining 3 min of DLE at 20 and 30 W. During the first minute of DLE at 40 W, MSNA (bursts/min) decreased by 18% (P < 0.05), but returned to control levels during the last minute of exercise. Because dynamic leg exercise in the upright position increases venous return, we postulated that upright DLE might increase cardiac filling pressures and stimulate the cardiopulmonary baroreceptors resulting in suppression of MSNA. To investigate this possibility, we measured MSNA and central venous pressure (CVP) during 4 min of both supine and upright DLE at 30 W. MAP, HR, and CVP increased and MSNA decreased from 30 +/- 3 to 22 +/- 3 bursts/min (mean exercise value; P < 0.05) during upright DLE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Nonuniform regional sympathetic nerve responses to hyperinsulinemia in rats.

The insulin hypothesis of hypertension proposes that hyperinsulinemia increases sympathetic nerve activity (SNA) and raises arterial pressure. The goals of this study were 1) to determine if hyperinsulinemia produces regionally uniform or nonuniform increases in SNA and 2) to test the hypothesis that spontaneously hypertensive rats (SHR) have exaggerated sympathoadrenal responses to hyperinsulinemia. We measured plasma insulin, blood glucose, mean arterial pressure, and adrenal, renal, and lumbar SNA in alpha-chloralose-anesthetized SHR and normotensive Wistar-Kyoto (WKY) rats before and during infusion of two doses of insulin for 60 min each while maintaining euglycemia. In WKY rats, graded increases in plasma insulin from 27 +/- 5 (SE) to 200 +/- 29 microU/ml increased lumbar SNA from 100% to 285 +/- 26% but failed to significantly increase adrenal or renal SNA. In SHR rats, similar increases in plasma insulin from 27 +/- 4 to 213 +/- 33 microU/ml caused significant increases in adrenal (100% to 174 +/- 16%) and lumbar (100% to 307 +/- 26%) SNA but not in renal SNA. Despite increases in SNA, mean arterial pressure did not increase significantly in either group of rats. We conclude that 1) hyperinsulinemic euglycemic clamp produces regionally nonuniform increases in sympathetic nerve activity, and 2) there is a potentiated increase in adrenal SNA in SHR compared with WKY rats during hyperinsulinemia, whereas lumbar SNA responses were similar in the two strains, and renal SNA did not increase in either strain.

Animals↗
PubMed1993

Augmentation of muscle sympathetic nerve activity during fatiguing isometric leg exercise.

Recent studies have shown a lack of an increase in muscle sympathetic nerve activity (MSNA) during leg exercise. Experiments using isometric knee extension (IKE) have shown a biphasic response in MSNA with a decrease during the 1st min and a return of MSNA to control levels during the 2nd min of IKE. Moreover, MSNA was not augmented during postexercise muscle ischemia (PEMI) of the exercising leg, suggesting that the muscle metaboreflex may have not been engaged in these experiments. The purpose of the present study was 1) to examine MSNA during IKE performed to fatigue to determine whether MSNA could be increased with leg exercise and 2) to determine whether increases in MSNA during fatiguing IKE were associated with an augmented MSNA response during PEMI. IKE was initially performed to fatigue at 30% of maximal voluntary contraction in the sitting position (n = 7; trial 1). IKE elicited a marked increase in mean arterial pressure and heart rate (P < 0.01). Total MSNA (burst frequency x mean burst amplitude; units) in the contralateral leg increased 96 +/- 40% (P < 0.01) above control levels during the final 30 s of IKE (207 +/- 23 s). Subjects (n = 8) then performed IKE to fatigue followed by PEMI (trial 2). MSNA in the contralateral leg increased 107 +/- 50% (P < 0.01) above control levels during the final 30 s of IKE (169 +/- 12 s) and remained significantly elevated during PEMI (83 +/- 40% above control), indicating that the muscle metaboreflex was engaged during fatiguing IKE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Effects of heart failure on baroreflex control of sympathetic neural activity.

Baroreflex control of heart rate, vascular resistance and norepinephrine is impaired in patients with heart failure, but recent animal studies demonstrate preserved baroreflex control of sympathetic nerve activity in this disorder. Studies were therefore performed to compare baroreflex control of efferent sympathetic nerve activity to muscle in 10 normal subjects (age mean +/- SEM 21 +/- 1 years) and in 11 patients with moderate to severe heart failure (age 48 +/- 5 years, New York Heart Association class II to IV, left ventricular ejection fraction 19 +/- 2%, pulmonary capillary wedge pressure 27 +/- 2 mm Hg, cardiac index 2.04 +/- 0.22 liters/min/m2). Baroreflex activation was produced by intravenous infusion of phenylephrine (0.5 to 2.0 micrograms/kg/min) and deactivation by infusion of nitroprusside (0.4 to 2.5 micrograms/kg/min). During phenylephrine infusion, comparable increases in mean arterial pressure were produced in normal subjects (89 +/- 2 to 99 +/- 3 mm Hg, p less than 0.01) and in patients with heart failure (90 +/- 2 to 99 +/- 3 mm Hg, p less than 0.01). The patients with heart failure exhibited significantly attenuated (p less than 0.01 for normal vs heart failure) decreases in heart rate (93 +/- 5 to 90 +/- 6 beats/min, p = not significant [NS]) compared with normal subjects (67 +/- 3 to 58 +/- 4 beats/min, p less than 0.01) and tended to demonstrate attenuated sympathoinhibitory responses to this pressor stimulus. More strikingly, patients with heart failure demonstrated significant impairment of baroreflex responses during nitroprusside-induced baroreceptor deactivation. In normal subjects, nitroprusside produced a decrease in mean arterial (90 +/- 2 to 80 +/- 3 mm Hg, p less than 0.001) and right atrial (4 +/- 1 to 2 +/- 1 mm Hg, p less than 0.01) pressures with a resultant reflex increase in heart rate (68 +/- 3 to 81 +/- 4 beats/min, p less than 0.001) and muscle sympathetic nerve activity (326 +/- 74 to 746 +/- 147 U/min, p less than 0.01). In patients with heart failure (n = 10), nitroprusside produced comparable (p = NS for normal vs heart failure) decreases in mean arterial (89 +/- 2 to 77 +/- 2 mm Hg, p less than 0.001) and right atrial (6 +/- 1 to 1 +/- 1 mm Hg, p less than 0.001) pressures, but did not significantly alter heart rate (91 +/- 6 to 97 +/- 4 beats/min, p = NS) or sympathetic nerve activity (936 +/- 155 to 1179 +/- 275 U/min, p = NS).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Parasympathetic hyperresponsiveness and bradyarrhythmias during apnoea in hypertension.

Voluntary end-expiratory apnoea in a 23-year-old asymptomatic mild hypertensive patient consistently elicited bradyarrhythmias (complete heart block and sinus pause) and sympathetic activation to muscle blood vessels, indicating simultaneous sympathetic and parasympathetic activation during apnoea. The sympathetic bradyarrhythmic response to apnoea was potentiated by hypoxia and eliminated by atropine. Baroreflex activation also attenuated the bradycardic response to apnoea. A 43-year-old hypertensive patient with sleep apnoea also exhibited bradyarrhythmias (sinus arrest for up to 10 s) and a fall in perfusion pressure to less than 50 mmHg during episodes of sleep apnoea. These cardiovascular changes were associated with a reduction in oxygen saturation to levels as low as 35%. Neither patient was on any medication. Simultaneous sympathetic and parasympathetic activation during episodes of apnoea may predispose to cardiovascular catastrophe. These chemoreflex mediated autonomic changes are inhibited by baroreflex activation. We propose that patients with impaired baroreflexes (patients with hypertension or heart failure and premature infants) may be especially susceptible to excessive autonomic responses to chemoreflex stimulation during periods of apnoea. In these patient groups, bradyarrhythmias, hypoxia, hypoperfusion and sympathetic activation during apnoea may predispose to sudden death.

Adult↗
PubMed1992

Forearm endurance training attenuates sympathetic nerve response to isometric handgrip in normal humans.

Recent evidence indicates that muscle ischemia and activation of the muscle chemoreflex are the principal stimuli to sympathetic nerve activity (SNA) during isometric exercise. We postulated that physical training would decrease muscle chemoreflex stimulation during isometric exercise and thereby attenuate the SNA response to exercise. We investigated the effects of 6 wk of unilateral handgrip endurance training on the responses to isometric handgrip (IHG: 33% of maximal voluntary contraction maintained for 2 min). In eight normal subjects the right arm underwent exercise training and the left arm sham training. We measured muscle SNA (peroneal nerve), heart rate, and blood pressure during IHG before vs. after endurance training (right arm) and sham training (left arm). Maximum work to fatigue (an index of training efficacy) was increased by 1,146% in the endurance-trained arm and by only 40% in the sham-trained arm. During isometric exercise of the right arm, SNA increased by 111 +/- 27% (SE) before training and by only 38 +/- 9% after training (P less than 0.05). Endurance training did not significantly affect the heart rate and blood pressure responses to IHG. We also measured the SNA response to 2 min of forearm ischemia after IHG in five subjects. Endurance training also attenuated the SNA response to postexercise forearm ischemia (P = 0.057). Sham training did not significantly affect the SNA responses to IHG or forearm ischemia. We conclude that endurance training decreases muscle chemoreflex stimulation during isometric exercise and thereby attenuates the sympathetic nerve response to IHG.

Adult↗
PubMed1992

Muscle sympathetic nerve responses to static leg exercise.

Previous studies of muscle sympathetic nerve activity (MSNA) during static exercise have employed predominantly the arms. These studies have revealed striking increases in arm and leg MSNA during static handgrip (SHG) and postexercise circulatory arrest (PECA). The purpose of this study was to examine MSNA during static leg exercise (SLE) at intensities and duration commonly used during SHG followed by PECA. During 2 min of SLE (static knee extension) at 10% of maximal voluntary contraction (MVC; n = 18) in the sitting position, mean arterial pressure and heart rate increased significantly. Surprisingly, MSNA in the contralateral leg did not increase above control levels during SLE but rather decreased (23 +/- 5%; P < 0.05) during the 1st min of SLE at 10% MVC. We compared MSNA responses to SHG and SLE (n = 8) at 30% MVC. SHG and SLE elicited comparable increases (P < 0.05) in arterial pressure and heart rate, but SHG elicited significant increases in MSNA, whereas SLE did not. During PECA after SHG and SLE, mean arterial pressure remained significantly above control. However, MSNA was unchanged during PECA after SLE but was significantly greater than control during PECA after SHG. Because previous studies have indicated differences in MSNA responses to the arm and leg, we measured arm and leg MSNA simultaneously in six subjects during SLE at 20% MVC and PECA. During SLE and PECA, MSNA in the contralateral arm and leg did not differ significantly from each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗
PubMed1992

Insulin increases sympathetic activity but not blood pressure in borderline hypertensive humans.

We have previously demonstrated that physiological hyperinsulinemia in normotensive humans increases sympathetic nerve activity but not arterial pressure since it also causes skeletal muscle vasodilation. However, in the presence of insulin resistance and/or hypertension, insulin may cause exaggerated sympathetic activation or impaired vasodilation and thus elevate arterial pressure. This study sought to determine if insulin causes a pressor response in borderline hypertensive humans by producing exaggerated increases in sympathetic neural outflow or impaired vasodilation. We recorded muscle sympathetic nerve activity (microneurography, peroneal nerve), forearm blood flow, heart rate, and blood pressure in 13 borderline hypertensive subjects during a 1-hour insulin infusion (38 microunits/m2/min) while holding blood glucose constant. Plasma insulin rose from 12 +/- 3 microunits/ml (mean +/- SEM) during control to 73 +/- 7 microunits/ml during insulin infusion and fell to 9 +/- 2 microunits/ml 2 hours after insulin infusion was stopped. Muscle sympathetic nerve activity, which averaged 25 +/- 2 bursts per minute in control, increased significantly during insulin infusion (+9 bursts per minute) and remained elevated 1.5 hours into recovery (+7 bursts per minute, p less than 0.001). Despite increased muscle sympathetic nerve activity, there were significant (p less than 0.001) increases in forearm blood flow and decreases in forearm vascular resistance during insulin infusion. Further, systolic and diastolic pressures fell approximately 3 and 6 mm Hg, respectively, during insulin infusion (p less than 0.01). This study suggests that acute physiological increases in plasma insulin elevate sympathetic neural outflow in borderline hypertensive humans but produce vasodilation and do not elevate arterial pressure.

Adult↗
PubMed1992

Naloxone potentiates cardiopulmonary baroreflex sympathetic control in normal humans.

Naloxone, an opioid antagonist, augments baroreflex mechanisms in animals; this occurrence suggests that endogenous opioids blunt baroreflex responses. Limited human studies suggest an inhibitory action of endogenous opioids on baroreflex-mediated vagal responses during arterial baroreceptor deactivation. To evaluate the potential effect of endogenous opioids on cardiopulmonary baroreflex mechanisms in humans, we measured arterial and central venous pressures, heart rate, and efferent muscle sympathetic nerve activity (MSNA, by peroneal microneurography) during unloading of cardiopulmonary baroreceptors with incremental lower body negative pressure (LBNP, from 0 to -15 mm Hg) and during the cold pressor test in 21 normal subjects (aged 24 +/- 1 [mean +/- SEM] years). In 14 subjects, we performed LBNP before and after naloxone (0.15 mg/kg i.v.) and placebo (n = 11) on separate days. In six of these 14 subjects and an additional seven subjects (n = 13), studies were also performed before and after administration of a lower dose of naloxone (0.075 mg/kg i.v.) on separate days. Neither dose of naloxone significantly altered control arterial or central venous pressures or heart rate. Control MSNA was reduced after the higher but not after the lower dose of naloxone. Comparable reductions in central venous pressure were produced by LBNP in all groups before and after naloxone or placebo, whereas LBNP did not alter arterial pressure. Cardiopulmonary baroreflex sympathetic sensitivity, which was derived as the slope of the linear regression relation between percent change in total MSNA (units) per absolute change in central venous pressure (mm Hg) during incremental LBNP, was significantly augmented after both the high dose (from 18.6 +/- 4.7%/mm Hg to 39.3 +/- 8.1%/mm Hg, p = 0.001) and low dose of naloxone, whereas placebo had no effect. MSNA responses to the cold pressor test were not altered by either dose of naloxone. Thus, naloxone selectively potentiates cardiopulmonary baroreflex regulation of sympathetic neural activity in normal humans. These findings suggest that endogenous opioids exert a tonic inhibitory effect on sympathetic responses to orthostatic stress in normal humans.

Adult↗
PubMed1992

Hydrogen ion concentration is not the sole determinant of muscle metaboreceptor responses in humans.

We examined the effects of exercise conditioning on muscle sympathetic nerve activity (MSNA) during handgrip and posthandgrip circulatory arrest (PHG-CA). Two conditioning stimuli were studied: forearm dominance and bodybuilding. Static handgrip at 30% maximal voluntary contraction followed by PHG-CA led to a rise in MSNA smaller in dominant than in nondominant forearms (99% vs. 222%; P less than 0.02) and in body builders than in normal volunteers (28% vs. 244%; P less than 0.01). Separate 31P NMR experiments showed no effect of dominance on forearm pH but a pH in bodybuilders higher (6.88) than in normal volunteers (6.79; P less than 0.02) during PHG-CA. Our second goal was to determine if factors besides attenuated [H+] contribute to this conditioning effect. If differences in MSNA during exercise were noted at the same pH, then other mechanisms must contribute to the training effect. We measured MSNA during ischemic fatiguing handgrip. No dominance or bodybuilding effect on pH was noted. However, we noted increases in MSNA smaller in dominant than nondominant forearms (212% vs. 322%; P less than 0.02) and in bodybuilders than in normal volunteers (161% vs. 334%; P less than 0.01). In summary, MSNA responses were less during exercise of conditioned limbs. Factors aside from a lessening of muscle acidosis contribute to this effect.

Adult↗
PubMed1991

Contrasting effects of digitalis and dobutamine on baroreflex sympathetic control in normal humans.

BACKGROUND: Digitalis glycosides augment cardiopulmonary baroreceptor mechanisms in animals. This could result from inotropic actions or from direct sensitization of cardiac mechanoreceptors. METHODS AND RESULTS: To determine if digitalis has similar actions in humans and to evaluate the mechanisms involved, we measured muscle sympathetic nerve activity (MSNA; microneurography) during unloading of cardiopulmonary baroreceptors with incremental lower body negative pressure (LBNP; 0 to -15 mm Hg) and during the cold pressor test in 22 normal subjects (age 22 +/- 1 year, mean +/- SEM). Arterial and central venous pressures, heart rate, and MSNA were measured during LBNP before and after intravenous digitalis (Cedilanid 0.02 ng/kg, n = 8), dobutamine (2.8 +/- 0.5 micrograms/kg/min, n = 8), or placebo (n = 6). Digitalis and dobutamine produced similar increases in baseline mean arterial pressure and decreases in central venous pressure and MSNA. LBNP produced similar decreases in central venous pressure in all groups before and after drug administration. The MSNA responses to LBNP were markedly potentiated by digitalis but not by dobutamine or placebo. CONCLUSIONS: Digitalis did not alter responses to the cold pressor test. Thus, digitalis selectively potentiated cardiopulmonary baroreflex regulation of sympathetic neural responses in normal humans, whereas dobutamine (another positive inotropic agent) did not produce this effect. We conclude that digitalis augments cardiopulmonary baroreflex control of sympathetic activity, probably by direct baroreceptor sensitization.

Adult↗
PubMed1991

Sympathetic neural contribution to salt-induced hypertension in Dahl rats.

The Dahl strain provides a model for examining mechanisms involved in the genetic sensitivity or resistance to salt-induced hypertension. Dahl salt-sensitive rats develop hypertension when fed a high salt diet; Dahl salt-resistant rats remain normotensive. Based on early experiments, it was thought that hypertension in Dahl salt-sensitive rats epitomized the overriding importance of renal and humoral mechanisms in salt-induced hypertension, but studies in the past 15 years have demonstrated that alterations in sympathetic neural mechanisms also participate critically in the genetic predisposition to salt-induced hypertension in Dahl salt-sensitive rats. This article briefly reviews sympathetic neural mechanisms in Dahl rats, including evidence for a role of afferent baroreceptor as well as central neural and peripheral adrenergic mechanisms in salt-induced hypertension in Dahl salt-sensitive rats.

Afferent Pathways↗