scholarly journals A reversal of fate : unravelling the role of central 5-HT in cardiorespiratory control in neonatal and adult rodents

2018 ◽  
Author(s):  
◽  
Jennifer Magnusson
Keyword(s):  
Blood Pressure ◽  
Physiological Role ◽  
Sudden Infant Death ◽  
Sudden Infant ◽  
Autonomic Tone ◽  
Neurogenic Hypertension ◽  
Cardiorespiratory Control ◽  
Arterial Blood ◽  
Lower Blood

We seek to address the extent to which a specific loss of 5-hydroxytryptamine (5-HT) affects the control of respiration, arterial blood pressure (ABP) and heart rate (HR) across vigilance-states based on existing evidence suggesting that 5-HT defects increase the risk for Sudden Infant Death Syndrome (SIDS) and neurogenic hypertension. SIDS is the leading cause of infant mortality between 1 month and 1 year of age, occurs during sleep, and up to 70% of all SIDS cases have at least one 5-HT system abnormality. Neonatal rodents lacking central 5-HT exhibit severe apneas, and a reduced ABP and HR. Central 5-HT has been implicated in the etiology of neurogenic hypertension, presumably due to projections of 5-HT neurons within the midline raphe to vagal and presympathetic regions of the brain. However, data from studies examining the specific role of central 5-HT function is conflicting or inconclusive. Neurogenic hypertension accounts for more than 90% of all hypertensive cases and the normal fall in ABP that occurs during non-rapid eye movement sleep is absent in some patients with hypertension. Understanding the mechanisms associated with the development of hypertension is critical not only to lower blood pressure, but to lower its associated cardiovascular events. The purpose of this dissertation is to examine the role of central 5-HT in the control of ABP during sleep and reveal, mechanistically, the physiological role of 5-HT in the autonomic control of ABP in neonatal and adult rodents. The overarching hypothesis for this dissertation is that central 5-HT is required for the maintenance of ABP and autonomic tone at rest in both neonatal and adult rodents.

Abstract 15839: Effect of Serotonin Neuron Depletion on Arterial Blood Pressure Regulation in Young Rats

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jennifer Magnusson ◽  
Kevin Cummings
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Recovery Period ◽  
Sudden Infant Death ◽  
Sudden Infant ◽  
Sprague Dawley ◽  
Baroreflex Control ◽  
Hypoxic Conditions ◽  
Arterial Blood

Infants dying of Sudden Infant Death Syndrome (SIDS) have reduced brainstem serotonin (5-hydroxytryptamine, 5-HT) where some cases die following episodes of severe bradycardia and hypoxemia. The specific role of central 5-HT in resting arterial blood pressure (BP) and on baroreflex sensitivity during neonatal life has not been studied. In adult animals, systemic depletion of 5-HT increases BP with no effect on heart rate (HR) and reduces the sensitivity of the baroreflex. Other studies have also shown that a loss of central 5-HT beginning in embryogenesis reduces resting BP and HR in adulthood. Based on these reports, we hypothesized that loss of brainstem 5-HT neurons in the neonatal period would reduce baseline BP and HR as well as reduce baroreflex gain. To test this, we utilized 3-week old Sprague Dawley rats treated centrally with 5,7-dihydroxytryptamine (5,7-DHT, n=4; ~120 ug in saline, i.c.v.), a chemical that is toxic to serotonergic neurons. Littermate controls were injected with saline (CTRL, n=5, ~3ul, i.c.v.). We measured BP with a femoral artery catheter. HR was derived from BP. Following a recovery period, we measured resting variables for 15 minutes and then injected phenylephrine (PE; 3mg/kg s.c.) followed by sodium nitroprusside (SNP; 2.5mg/kg s.c.), separated by 15 minutes, to induce pressor or depressor responses, respectively. For both responses, baroreflex gain was calculated as the [[Unable to Display Character: &#8710;]]HR at the maximum [[Unable to Display Character: &#8710;]]BP following drug injection. We found that a loss of 5-HT neurons did not alter baseline BP (p>0.05) but did reduce baseline HR when compared to control littermates (p<0.02). 5-HT neuron deficiency tended to reduce baroreflex gain in response to PE (CTRL: -2.756 ± 0.483 beats/mmHg; 5,7-DHT: -1.499 ± 0.348 beats/mmHg; p=0.058), but not SNP (CTRL: -2.408 ± 0.351 beats/mmHg; 5,7-DHT: -3.316 ± 1.214 beats/mmHg; p>0.05). Our data indicate that brainstem 5-HT maintains resting HR, and is involved in baroreflex control of HR in response to hypertensive stimuli. Reduced brainstem 5-HT may predispose an infant to SIDS via altered autonomic control of BP and HR. The role of 5-HT in BP regulation during hypoxic conditions remains to be elucidated.

scholarly journals Maternal dietary tryptophan deficiency alters cardiorespiratory control in rat pups

2011 ◽  
Vol 110 (2) ◽  
pp. 318-328 ◽  
Author(s):  
Eliana M. Penatti ◽  
Alexis E. Barina ◽  
Sharat Raju ◽  
Aihua Li ◽  
Hannah C. Kinney ◽  
...  
Keyword(s):  
Brain Stem ◽  
Sudden Infant Death ◽  
Normal Weight ◽  
Sudden Infant ◽  
Postnatal Life ◽  
Cardiorespiratory Control ◽  
Cardiorespiratory Function ◽  
Rat Pups ◽  
Neuronal Number

Malnutrition during pregnancy adversely affects postnatal forebrain development; its effect upon brain stem development is less certain. To evaluate the role of tryptophan [critical for serotonin (5-HT) synthesis] on brain stem 5-HT and the development of cardiorespiratory function, we fed dams a diet ∼45% deficient in tryptophan during gestation and early postnatal life and studied cardiorespiratory variables in the developing pups. Deficient pups were of normal weight at postnatal day (P)5 but weighed less than control pups at P15 and P25 ( P < 0.001) and had lower body temperatures at P15 ( P < 0.001) and P25 ( P < 0.05; females only). Oxygen consumption (V̇o2) was unaffected. At P15, deficient pups had an altered breathing pattern and slower heart rates. At P25, they had significantly lower ventilation (V̇e) and V̇e-to-V̇o2 ratios in both air and 7% CO2. The ventilatory response to CO2 (% increase in V̇e/V̇o2) was significantly increased at P5 (males) and reduced at P15 and P25 (males and females). Deficient pups had 41–56% less medullary 5-HT ( P < 0.01) compared with control pups, without a difference in 5-HT neuronal number. These data indicate important interactions between nutrition, brain stem physiology, and age that are potentially relevant to understanding 5-HT deficiency in the sudden infant death syndrome.

scholarly journals Sex- and age-based differences in the effect of central serotonin on arterial blood pressure regulation

2020 ◽  
Vol 129 (6) ◽  
pp. 1310-1323
Author(s):  
Jennifer L. Magnusson ◽  
Craig A. Emter ◽  
Kevin J. Cummings
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Nrem Sleep ◽  
Blood Pressure Regulation ◽  
Pressure Regulation ◽  
Adult Rats ◽  
Arterial Blood ◽  
Serotonin Neurons ◽  
Older Males

The role of serotonin in arterial blood pressure (ABP) regulation across states of vigilance is unknown. We hypothesized that adult rats devoid of CNS serotonin (TPH2−/−) have low ABP in wakefulness and NREM sleep, when serotonin neurons are active. However, TPH2−/− rats experience higher ABP than TPH2+/+ rats in wakefulness and REM only, a phenotype present only in older males and not females. CNS serotonin may be critical for preventing high ABP in males with aging.

scholarly journals Accumulation of Prostacyclin in Rat Brain during Haemorrhagic Hypotension—Possible Role of PGI2 in Autoregulation

1984 ◽  
Vol 4 (1) ◽  
pp. 107-109 ◽  
Author(s):  
E. Shohami ◽  
A. Sidi
Keyword(s):  
Blood Pressure ◽  
Steady State ◽  
Control Group ◽  
Prostaglandin E ◽  
Cortical Tissue ◽  
Arterial Blood ◽  
Haemorrhagic Hypotension ◽  
Potent Vasodilator ◽  
Prostaglandin F

The effect of haemorrhagic hypotension on the levels of prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6-keto prostaglandin F1α (6-keto-PGF1α) in cortical tissue of rats was studied. Lightly anesthetized rats were subjected to steady-state hypotension for 15 min, with a mean arterial blood pressure of 80, 60, and 40 mm Hg, and compared to a control group of normotensive rats. No significant change was found in the levels of PGE2 and TXB2. The level of 6-keto-PGF1α increased from 7.8 ± 0.9 to 14.1 ± 1.9 pg/mg protein (p < 0.02) at 80 mm Hg. Our findings suggest that prostacyclin, which is a potent vasodilator, might play a role in setting the lower limit of the autoregulation range.

scholarly journals Role of the medulla oblongata in normal and high arterial blood pressure regulation: the contribution of Escola Paulista de Medicina - UNIFESP

2009 ◽  
Vol 81 (3) ◽  
pp. 589-603 ◽  
Author(s):  
Sergio L. Cravo ◽  
Ruy R. Campos ◽  
Eduardo Colombari ◽  
Mônica A. Sato ◽  
Cássia M. Bergamaschi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Medulla Oblongata ◽  
Neural Circuits ◽  
Ventrolateral Medulla ◽  
Vasomotor Tone ◽  
Arterial Blood ◽  
Pathological Conditions ◽  
De Medicina

Several forms of experimental evidence gathered in the last 37 years have unequivocally established that the medulla oblongata harbors the main neural circuits responsible for generating the vasomotor tone and regulating arterial blood pressure. Our current understanding of this circuitry derives mainly from the studies of Pedro Guertzenstein, a former student who became Professor of Physiology at UNIFESP later, and his colleagues. In this review, we have summarized the main findings as well as our collaboration to a further understanding of the ventrolateral medulla and the control of arterial blood pressure under normal and pathological conditions.

scholarly journals Rostral ventral medulla 5-HT1A receptors selectively inhibit the somatosympathetic reflex

2001 ◽  
Vol 280 (5) ◽  
pp. R1261-R1268 ◽  
Author(s):  
Takashi Miyawaki ◽  
Ann K. Goodchild ◽  
Paul M. Pilowsky
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Sympathetic Nerve Activity ◽  
Selective Inhibition ◽  
Inhibitory Effect ◽  
Ventrolateral Medulla ◽  
Arterial Blood ◽  
Potent Inhibition ◽  
Somatosympathetic Reflex

The role of the 5-hydroxytryptamine (5-HT1A) receptors in the rostral ventrolateral medulla (RVLM) on somatosympathetic, baroreceptor, and chemoreceptor reflexes was examined in anesthetized rats. Microinjection of the selective 5-HT1A agonist 8-hydroxy-di- n-propylamino tetralin (8-OH-DPAT) decreased arterial blood pressure and splanchnic sympathetic nerve activity (SNA). Electrical stimulation of the hindlimb evoked early and late excitatory sympathetic responses. Bilateral microinjection in the RVLM of 8-OH-DPAT markedly attenuated both the early and late responses. This potent inhibition of the somatosympathetic reflex persisted even after SNA and arterial blood pressure returned to preinjection levels. Preinjection of the selective 5-HT1A antagonist NAN-190 in the RVLM blocked the sympathoinhibitory effect of 8-OH-DPAT and attenuated the inhibitory effect on the somatosympathetic reflex. 8-OH-DPAT injected in the RVLM did not affect baroreceptor or chemoreceptor reflexes. Our findings suggest that activation of 5-HT1A receptors in the RVLM exerts a potent, selective inhibition on the somatosympathetic reflex.

scholarly journals Prospective Randomized Controlled Study to assess the Role of Dexmedetomidine on Perioperative Hemodynamics in Patients with Supratentorial Tumor undergoing Surgery

2017 ◽  
Vol 2 (1) ◽  
pp. 14-17
Author(s):  
Sachin Vaishnav ◽  
Anita Shetty ◽  
Manjula Sarkar
Keyword(s):  
Blood Pressure ◽  
Placebo Group ◽  
Arterial Blood Pressure ◽  
Randomized Controlled Study ◽  
Controlled Study ◽  
Randomized Controlled ◽  
Arterial Blood ◽  
Supratentorial Tumor ◽  
Duration Of Surgery

ABSTRACT The stress response to an intense painful surgical stimulus is characterized by activation of the sympathetic nervous system and an increased secretion of the stress hormones. The ability of the alpha agonist dexmedetomidine (DEX) to decrease heart rate (HR) and arterial blood pressure in perioperative period was tested. One hundred and thirty two patients undergoing craniotomy for supratentorial tumor were randomly distributed to receive either saline (B group) or DEX (A group). The placebo group received saline, whereas the treatment group (A group) received a single bolus dose of DEX (1μg/kg) intravenously over 10 minutes before induction of anesthesia. Hemodynamic parameters, such as HR and arterial blood pressure were measured. Both the groups were comparable with respect to age, sex, American Society for Anesthesiologist grade, and duration of surgery. The arterial blood pressure and HR were found to be lower in the DEX group when compared with the placebo group. How to cite this article Vaishnav S, Shetty A, Sarkar M. Prospective Randomized Controlled Study to assess the Role of Dexmedetomidine on Perioperative Hemodynamics in Patients with Supratentorial Tumor undergoing Surgery. Res Inno in Anesth 2017;2(1):14-17.

scholarly journals The role of infectious agents in sudden infant death syndrome

1994 ◽  
Vol 9 (2) ◽  
pp. 91-100 ◽  
Author(s):  
C. Caroline Blackwell ◽  
Donald M. Weir ◽  
Anthony Busuttil ◽  
Abdulrahman T. Saadi ◽  
Steven D. Essery ◽  
...  
Keyword(s):  
Sudden Infant Death Syndrome ◽  
Infant Death ◽  
Sudden Infant Death ◽  
Sudden Infant ◽  
Infectious Agents
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