Mechanisms of acute cardiovascular response  to periodic apneas in sedated pigs

This study was designed to evaluate the importance of sympathoadrenal activation in the acute cardiovascular response to apneas and the role of hypoxemia in this response. In addition, we evaluated the contribution of the vagus nerve to apnea responses after chemical sympathectomy. In six pigs preinstrumented with an electromagnetic flow probe and five nonpreinstrumented pigs, effects of periodic nonobstructive apneas were tested under the following six conditions: room air breathing, 100% O2 supplementation, both repeated after administration of hexamethonium (Hex), and both repeated again after bilateral vagotomy in addition to Hex. With room air apneas, during the apnea cycle, there were increases in mean arterial pressure (MAP; from baseline of 108 ± 4 to 124 ± 6 Torr, P < 0.01), plasma norepinephrine (from 681 ± 99 to 1,825 ± 578 pg/ml, P < 0.05), and epinephrine (from 191 ± 67 to 1,245 ± 685 pg/ml, P < 0.05) but decreases in cardiac output (CO; from 3.3 ± 0.6 to 2.4 ± 0.3 l/min, P < 0.01) and cervical sympathetic nerve activity. With O2supplementation relative to baseline, apneas were associated with small increases in MAP (from 112 ± 4 to 118 ± 3 Torr, P < 0.01) and norepinephrine (from 675 ± 97 to 861 ± 170 pg/ml, P< 0.05). After Hex, apneas with room air were associated with small increases in MAP (from 103 ± 6 to 109 ± 6 Torr, P < 0.05) and epinephrine (from 136 ± 45 to 666 ± 467 pg/ml, P < 0.05) and decreases in CO (from 3.6 ± 0.4 to 3.2 ± 0.5 l/min, P < 0.05). After Hex, apneas with O2 supplementation were associated with decreased MAP (from 107 ± 5 to 100 ± 5 Torr, P < 0.05) and no other changes. After vagotomy + Hex, with room air and O2 supplementation, apneas were associated with decreased MAP (from 98 ± 6 to 76 ± 7 and from 103 ± 7 to 95 ± 6 Torr, respectively, both P < 0.01) but increased CO [from 2.7 ± 0.3 to 3.2 ± 0.4 l/min ( P < 0.05) and from 2.4 ± 0.2 to 2.7 ± 0.2 l/min ( P < 0.01), respectively]. We conclude that sympathoadrenal activation is the major pressor mechanism during apneas. Cervical sympathetic nerve activity does not reflect overall sympathoadrenal activity during apneas. Hypoxemia is an important but not the sole trigger factor for sympathoadrenal activation. There is an important vagally mediated reflex that contributes to the pressor response to apneas.

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Suppression of inferior alveolar nerve-induced vasoconstrictor response by ongoing cervical sympathetic nerve activity in cat

Archives of Oral Biology ◽

10.1016/j.archoralbio.2004.07.008 ◽

2004 ◽

Vol 49 (12) ◽

pp. 1035-1041 ◽

Cited By ~ 3

Author(s):

H. Izumi ◽

I. Nakamura ◽

H. Ishii

Keyword(s):

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Inferior Alveolar Nerve ◽

Nerve Activity ◽

Vasoconstrictor Response ◽

Cervical Sympathetic ◽

Cervical Sympathetic Nerve

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Sympathoinhibition and its reversal by naloxone during hemorrhage

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1992.262.3.r444 ◽

1992 ◽

Vol 262 (3) ◽

pp. R444-R451 ◽

Cited By ~ 9

Author(s):

E. M. Hasser ◽

J. C. Schadt

Keyword(s):

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Pressor Response ◽

Plasma Norepinephrine ◽

Adrenergic Blockade ◽

Nerve Activity ◽

Renal Sympathetic Nerve Activity ◽

Alpha Blockade ◽

Activity Decrease ◽

Renal Sympathetic

During hemorrhagic hypotension, vascular resistance, plasma norepinephrine, and sympathetic nerve activity decrease. Naloxone reverses these effects. We hypothesized that increased sympathetic nerve activity was specific to naloxone and not secondary to the pressor response. Conscious rabbits were hemorrhaged until mean arterial pressure (MAP) was less than 40 mmHg, given naloxone (3 mg/kg) or saline, and monitored for 5 min. In some animals, we attenuated naloxone's pressor response with alpha-adrenergic blockade or mimicked the pressor response by infusion of phenylephrine. During nonhypotensive hemorrhage, heart rate and renal sympathetic nerve activity (RSNA) increased significantly. During hypotensive hemorrhage, RSNA decreased to significantly less than prehemorrhage control values. After saline treatment, RSNA did not increase. Naloxone significantly increased MAP and RSNA. alpha-Blockade reduced the pressor response to naloxone but not the increase in RSNA. Phenylephrine increased MAP to a level similar to naloxone, but RSNA remained suppressed. Reinfusion of hemorrhaged blood reduced RSNA in all groups treated with naloxone. These data suggest that hypotensive hemorrhage is associated with sympathoinhibition that is not transient. In addition, the pressor response to naloxone is not required for its sympathoexcitatory effects.

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Effect of Pneumoperitoneum on Cervical Sympathetic Nerve Activity and Hemodynamics

Anesthesiology ◽

10.1097/00000542-199809120-00059 ◽

1998 ◽

Vol 89 (Supplement) ◽

pp. 647A

Author(s):

H Aono ◽

A Takeda ◽

K Shinohara ◽

K T Benson ◽

H Goto

Keyword(s):

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Nerve Activity ◽

Cervical Sympathetic ◽

Cervical Sympathetic Nerve

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Regional hemodynamic and baroreflex effects of endothelin in rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1989.257.3.h918 ◽

1989 ◽

Vol 257 (3) ◽

pp. H918-H926 ◽

Cited By ~ 5

Author(s):

M. M. Knuepfer ◽

S. P. Han ◽

A. J. Trapani ◽

K. F. Fok ◽

T. C. Westfall

Keyword(s):

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Pressor Response ◽

Cardiovascular Responses ◽

Nerve Activity ◽

Anesthetized Rats ◽

Pressor Responses ◽

Regional Hemodynamics ◽

Potent Vasoconstrictor ◽

Baroreceptor Reflex Control

Endothelin is a peptide with potent, long-lasting pressor effects characterized by increases in mesenteric and hindquarters vascular resistance and bradycardia following an initial, transient depressor response. This study examined the mechanisms of action of endothelin on regional hemodynamics in conscious, freely moving rats and on baroreflex sensitivity both in conscious and chloralose-anesthetized rats. The pressor response to endothelin (0.67 nmol/kg) was attenuated by nifedipine (25 micrograms/kg) and augmented by chloralose anesthesia. The bradycardia was attenuated by pentolinium (10 mg/kg), atropine methyl sulfate (0.5 mg/kg), or chloralose anesthesia. Hindquarter vaso-constriction was attenuated by nifedipine, pentolinium, and atropine, whereas mesenteric vasoconstriction was less sensitive to blockade. The vasopressin V1 antagonist, [d(CH2)5Tyr(Me)]-AVP (20 micrograms/kg), indomethacin (5 mg/kg), or verapamil (150 micrograms/kg) did not affect any of these cardiovascular responses. Renal sympathetic nerve activity was reduced similarly in chloralose-anesthetized rats to pressor responses elicited by either phenylephrine or endothelin, and the slope of the baro-reflex function curve after endothelin was similar to that of phenylephrine. These results suggest that endothelin is a potent vasoconstrictor in which its action on visceral and skeletal muscle vasculature is mediated by somewhat different mechanisms. Endothelin does not alter baroreceptor reflex control of sympathetic nerve activity or heart rate.

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Alterations in sympathetic neurovascular transduction during acute hypoxia in humans

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00071.2013 ◽

2013 ◽

Vol 304 (11) ◽

pp. R959-R965 ◽

Cited By ~ 6

Author(s):

Can Ozan Tan ◽

Yu-Chieh Tzeng ◽

Jason W. Hamner ◽

Renaud Tamisier ◽

J. Andrew Taylor

Keyword(s):

Heart Rate ◽

Sympathetic Nerve ◽

Sympathetic Activity ◽

Sympathetic Nerve Activity ◽

Pressor Response ◽

Acute Hypoxia ◽

Sympathetic Outflow ◽

Isometric Handgrip ◽

Nerve Activity ◽

Hypoxic Exercise

Resting vascular sympathetic outflow is significantly increased during and beyond exposure to acute hypoxia without a parallel increase in either resistance or pressure. This uncoupling may indicate a reduction in the ability of sympathetic outflow to effect vascular responses (sympathetic transduction). However, the effect of hypoxia on sympathetic transduction has not been explored. We hypothesized that transduction would either remain unchanged or be reduced by isocapnic hypoxia. In 11 young healthy individuals, we measured beat-by-beat pressure, multiunit sympathetic nerve activity, and popliteal blood flow velocity at rest and during isometric handgrip exercise to fatigue, before and during isocapnic hypoxia (∼80% SpO2), and derived sympathetic transduction for each subject via a transfer function that reflects Poiseuille's law of flow. During hypoxia, heart rate and sympathetic nerve activity increased, whereas pressure and flow remained unchanged. Both normoxic and hypoxic exercise elicited significant increases in heart rate, pressure, and sympathetic activity, although sympathetic responses to hypoxic exercise were blunted. Hypoxia slightly increased the gain relation between pressure and flow (0.062 ± 0.006 vs. 0.074 ± 0.004 cm·s−1·mmHg−1; P = 0.04), but markedly increased sympathetic transduction (−0.024 ± 0.005 vs. −0.042 ± 0.007 cm·s−1·spike−1; P < 0.01). The pressor response to isometric handgrip was similar during normoxic and hypoxic exercise due to the balance of interactions among the tachycardia, sympathoexcitation, and transduction. This indicates that the ability of sympathetic activity to affect vasoconstriction is enhanced during brief exposure to isocapnic hypoxia, and this appears to offset the potent vasodilatory stimulus of hypoxia.

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Pulse-synchronous sympathetic burst power as a new index of sympathoexcitation in patients with heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00252.2003 ◽

2004 ◽

Vol 287 (4) ◽

pp. H1821-H1827 ◽

Cited By ~ 4

Author(s):

Yoshitaka Oda ◽

Hidetsugu Asanoi ◽

Hiroshi Ueno ◽

Kunihiro Yamada ◽

Shuji Joho ◽

...

Keyword(s):

Heart Failure ◽

Sympathetic Nerve ◽

Sympathetic Activity ◽

Sympathetic Nerve Activity ◽

Class Ii ◽

Plasma Norepinephrine ◽

Class Iii ◽

Nerve Activity ◽

Significant Difference ◽

Patients With Heart Failure

The upper limit of incidence of muscle sympathetic neural bursts can lead to underestimation of sympathetic activity in patients with severe heart failure. This study aimed to evaluate the pulse-synchronous burst power of muscle sympathetic nerve activity (MSNA) as a more specific indicator that could discriminate sympathetic activity in patients with heart failure. In 54 patients with heart failure, the pulse-synchronous burst power at the mean heart rate was quantified by spectral analysis of MSNA. Thirteen patients received a central sympatholytic agent (guanfacine) for 5 days to validate the feasibility of this new index. Both burst incidence and plasma norepinephrine level showed no significant difference between patients in New York Heart Association functional class III (94 ± 6 per 100 heartbeats and 477 ± 219 pg/ml, respectively) and class II (79 ± 14 per 100 heartbeats and 424 ± 268 pg/ml, respectively). In contrast, the burst power was useful for discriminating patients in class III from those in class II (61 ± 8% vs. 39 ± 10%; P < 0.05). Inhibition of sympathetic nerve activity by guanfacine was more sensitively reflected by the change of burst power (−36 ± 25%) than by that of burst incidence (−12 ± 14%; P < 0.001). The sympathetic burst power reflects both burst frequency and amplitude independently of the absolute values and provides a sensitive new index for interindividual comparisons of sympathetic activity in patients with heart failure.

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Does infusion of ANG II increase muscle sympathetic nerve activity in patients with primary aldosteronism?

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00471.2007 ◽

2008 ◽

Vol 294 (6) ◽

pp. R1873-R1879 ◽

Cited By ~ 6

Author(s):

Toshiyoshi Matsukawa ◽

Takenori Miyamoto

Keyword(s):

Primary Aldosteronism ◽

Sympathetic Nerve ◽

Baroreflex Sensitivity ◽

Sympathetic Nerve Activity ◽

Pressor Response ◽

Muscle Sympathetic Nerve Activity ◽

Venous Pressure ◽

Ang Ii ◽

Nerve Activity ◽

Unilateral Adrenalectomy

Patients with primary aldosteronism (PA) were shown to have suppressed muscle sympathetic nerve activity (MSNA) in our previous study. Although baroreflex inhibition probably accounts in part for this reduced MSNA in PA, we hypothesized that the lowered activity of the renin-angiotensin system in PA may also contribute to the suppressed SNA. We recorded MSNA in 9 PA and 16 age-matched normotensive controls (NC). In PA, the resting mean blood pressure (MBP) and serum sodium concentrations were increased, and MSNA was reduced. We examined the effects of infusion of a high physiological dose of ANG II (5.0 ng·kg−1·min−1) on MSNA in 6 of 9 PA and 9 of 16 NC. Infusion of ANG II caused a greater pressor response in PA than NC, but, in spite of the greater increase in pressure, MSNA increased in PA, whereas it decreased in NC. Simultaneous infusion of nitroprusside and ANG II, to maintain central venous pressure at the baseline level and reduce the elevation in MBP induced by ANG II, caused significantly greater increases in MSNA in PA than in NC. Baroreflex sensitivity of heart rate, estimated during phenylephrine infusions, was reduced in PA, but baroreflex sensitivity of MSNA was unchanged in PA compared with NC. All the abnormalities in PA were eliminated following unilateral adrenalectomy. In conclusion, the suppressed SNA in PA depends in part on the low level of ANG II in these patients.

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Bradykinin does not acutely sensitize the reflex pressor response during hindlimb skeletal muscle stretch in decerebrate rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00187.2017 ◽

2017 ◽

Vol 313 (4) ◽

pp. R463-R472 ◽

Cited By ~ 4

Author(s):

Korynne S. Rollins ◽

Joshua R. Smith ◽

Peter J. Esau ◽

Evan A. Kempf ◽

Tyler D. Hopkins ◽

...

Keyword(s):

Blood Pressure ◽

Skeletal Muscle ◽

Femoral Artery ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Pressor Response ◽

Nerve Activity ◽

Muscle Stretch ◽

Renal Sympathetic Nerve Activity ◽

Hindlimb Muscle

Hindlimb skeletal muscle stretch (i.e., selective activation of the muscle mechanoreflex) in decerebrate rats evokes reflex increases in blood pressure and sympathetic nerve activity. Bradykinin has been found to sensitize mechanogated channels through a bradykinin B2 receptor-dependent mechanism. Moreover, bradykinin B2 receptor expression on sensory neurons is increased following chronic femoral artery ligation in the rat (a model of simulated peripheral artery disease). We tested the hypothesis that injection of bradykinin into the arterial supply of a hindlimb in decerebrate, unanesthetized rats would acutely augment (i.e., sensitize) the increase in blood pressure and renal sympathetic nerve activity during hindlimb muscle stretch to a greater extent in rats with a ligated femoral artery than in rats with a freely perfused femoral artery. The pressor response during static hindlimb muscle stretch was compared before and after hindlimb arterial injection of 0.5 µg of bradykinin. Injection of bradykinin increased blood pressure to a greater extent in “ligated” ( n = 10) than “freely perfused” ( n = 10) rats. The increase in blood pressure during hindlimb muscle stretch, however, was not different before vs. after bradykinin injection in freely perfused (14 ± 2 and 15 ± 2 mmHg for pre- and post-bradykinin, respectively, P = 0.62) or ligated (15 ± 3 and 14 ± 2 mmHg for pre- and post-bradykinin, respectively, P = 0.80) rats. Likewise, the increase in renal sympathetic nerve activity during stretch was not different before vs. after bradykinin injection in either group of rats. We conclude that bradykinin did not acutely sensitize the pressor response during hindlimb skeletal muscle stretch in freely perfused or ligated decerebrate rats.

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Influence of age and sex on the pressor response following a spontaneous burst of muscle sympathetic nerve activity

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01105.2011 ◽

2012 ◽

Vol 302 (11) ◽

pp. H2419-H2427 ◽

Cited By ~ 54

Author(s):

Lauro C. Vianna ◽

Emma C. Hart ◽

Seth T. Fairfax ◽

Nisha Charkoudian ◽

Michael J. Joyner ◽

...

Keyword(s):

Postmenopausal Women ◽

Sympathetic Nerve ◽

Healthy Aging ◽

Sympathetic Nerve Activity ◽

Pressor Response ◽

Muscle Sympathetic Nerve Activity ◽

Older Men ◽

Nerve Activity ◽

Arterial Blood ◽

Age And Sex

The sympathetic nervous system is critical for the beat-to-beat regulation of arterial blood pressure (BP). Although studies have examined age- and sex-related effects on BP control, findings are inconsistent and limited data are available in postmenopausal women. In addition, the majority of studies have focused on time-averaged responses without consideration for potential beat-to-beat alterations. Thus we examined whether the ability of muscle sympathetic nerve activity (MSNA) to modulate BP on a beat-to-beat basis is affected by age or sex. BP and MSNA were measured during supine rest in 40 young (20 men) and 40 older (20 men) healthy subjects. Beat-to-beat fluctuations in mean arterial pressure (MAP) were characterized for 15 cardiac cycles after each MSNA burst using signal averaging. The rise in MAP following an MSNA burst was similar between young men and women (+2.64 ± 0.3 vs. +2.57 ± 0.3 mmHg, respectively). However, the magnitude of the increase in MAP after an MSNA burst was reduced in older compared with young subjects ( P < 0.05). Moreover, the attenuation of the pressor response was greater in older women (+1.20 ± 0.1 mmHg) compared with older men (+1.72 ± 0.2 mmHg; P < 0.05). Interestingly, in all groups, MAP consistently decreased after cardiac cycles without MSNA bursts (nonbursts) with the magnitude of fall greatest in older men. In summary, healthy aging is associated with an attenuated beat-to-beat increase in BP after a spontaneous MSNA burst, and this attenuation is more pronounced in postmenopausal women. Furthermore, our nonburst findings highlight the importance of sympathetic vasoconstrictor activity to maintain beat-to-beat BP, particularly in older men.

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