Increased Sensitivity of the Baroreceptor Reflex after Bacterial Endotoxin

Rogausch, H; Vo, N G; Rey, Adriana del; Besedovsky, Hugo O.

doi:10.1111/j.1749-6632.2000.tb05380.x

Cited by 19 publications

(11 citation statements)

References 9 publications

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“…In contrast, the net blood pressure increase in response to infusion of the ␣ 1 -agonist phenylephrine was not altered, indicating that the (peripheral) vascular responsiveness to ␣-adrenergic stimulation was well preserved. This is in accordance with previous observations in rodents (27).…”

Section: Discussionsupporting

confidence: 94%

Endotoxemia causes central downregulation of sympathetic vasomotor tone in healthy humans

Sayk

Vietheer

Schaaf

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Experimental endotoxemia as a model of the initial septic response affects the autonomic nervous system with profound cardiovascular sequelae. Whether the postsynaptic sympathoneural activity to the muscle vascular bed is altered in the early septic phase remains to be determined. The present study aimed to elucidate the early effects of LPS on muscle sympathetic nerve activity (MSNA) and cardiovascular regulation in healthy humans. Young, healthy volunteers randomly received either an LPS bolus (4 ng/kg body wt, n = 11) or placebo (saline; n = 7). Experimental baroreflex assessment (baseline measurements followed by infusion of vasoactive drugs nitroprusside/phenylephrine) was done prior to and 90 min following LPS or placebo challenge. MSNA, heart rate, blood pressure, and blood levels of catecholamines, TNF-alpha and IL-6 were measured sequentially. Endotoxin but not placebo-induced flu-like symptoms and elevated cytokine levels. In contrast to placebo, LPS significantly suppressed MSNA burst frequency 90 min after injection [mean +/- SE: 12.1 +/- 2.9 vs. 27.5 +/- 3.3 burst/min (post- vs. pre-LPS); P < 0.005] but increased heart rate [78.4 +/- 3.1 vs. 60.6 +/- 2.0 beats/min (post- vs. pre-LPS); P < 0.001]. Baseline blood pressure was not altered, but baroreflex testing demonstrated a blunted MSNA response and uncoupling of heart rate modulation to blood pressure changes in the endotoxin group. We conclude that endotoxin challenge in healthy humans has rapid suppressive effects on postsynaptic sympathetic nerve activity to the muscle vascular bed and alters baroreflex function which may contribute to the untoward cardiovascular effects of sepsis.

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Section: Discussionsupporting

confidence: 94%

Endotoxemia causes central downregulation of sympathetic vasomotor tone in healthy humans

Sayk

Vietheer

Schaaf

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Four, previous studies on the baroreflex function during infusion of bacterial endotoxins had limitations that were avoided in the present study (8,32). A most important limitation was that in previous studies baroreceptors were stimulated and unloaded by vasoactive drug administration.…”

Section: Discussionmentioning

confidence: 87%

Infusion of Escherichia coli Lipopolysaccharide Toxin in Rats Produces an Early and Severe Impairment of Baroreflex Function in Absence of Blood Pressure Changes

Radaelli

Castiglioni

Cerrito

et al. 2013

Shock

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The assessment of baroreflex function since the first appearance of endotoxemia is important because the arterial baroreflex should exert a protective role during sepsis. Nevertheless, contrasting results were previously reported. This could be due to the hemodynamic instability characterizing this condition that may per se interfere with reflex cardiovascular adjustments. The aim of our study was therefore to study the baroreflex function (a) since the very beginning of infusion of Escherichia coli lipopolysaccharide (LPS) toxin and (b) in absence of the unloading effect produced by a decrease in blood pressure. Lipopolysaccharide was infused in 10 rats for 20 min at the infusion rate of 0.05 mg · kg · min. Blood pressure was continuously measured before, during, and after infusion, and the baroreflex function was evaluated analyzing spontaneous fluctuations of systolic blood pressure and pulse interval by the sequence and transfer-function techniques. Plasma concentrations of inflammatory (interleukin 6, tumor necrosis factor α) and anti-inflammatory (interleukin 10) cytokines were measured in other eight rats, similarly instrumented, four of which receiving the same LPS infusion. We found that blood pressure levels did not change with the infusion of LPS, whereas inflammatory cytokines increased significantly. The baroreflex sensitivity was significantly reduced 10 min after the beginning of LPS infusion, reached values about half those at baseline within 15 min after the start of infusion, and remained significantly low after the end of infusion. In conclusion, we documented that septic shock inducing LPS infusion is responsible for a very rapid impairment of the baroreflex function, independent from the level of blood pressure.

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“…Gupta and Sharma [71] have also demonstrated that the fall in blood pressure, which occurs 2 h after LPS injection, is associated with an increase in aortic iNOS and eNOS protein expression, and systemic and tissue nitrate+nitrite (NO X ) levels. Compensatory mechanisms, including activation of renin-angiotensin-aldosteron system, increased sensitivity of baroreceptor reflex mechanisms, and increased production of endothelin-1 and cathecolamines, which are known to activate phospholipase A 2 and release arachidonic acid from tissue lipids, and results in prostaglandin synthesis, and also stimulate production of reactive nitrogen and oxygen species, have also been reported to be responsible for the changes in the formation of vasoregulatory molecules that could contribute to the fall in blood pressure during the early phase of LPS-induced endotoxemia [67–76]. Therefore, the vasodilator prostaglandins and NO could cause a decrease in blood pressure which is followed by increased expression of COX-2 and iNOS and decreased expression of CYP4A, resulting in sustained decrease in blood pressure.…”

Section: Discussionmentioning

confidence: 99%

NS-398 reverses hypotension in endotoxemic rats: Contribution of eicosanoids, NO, and peroxynitrite

Tunçtan¹,

Sarı²,

Kacan³

et al. 2013

Prostaglandins & Other Lipid Mediators

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We have previously demonstrated that inhibition of vasodilator prostanoids, PGI2 and PGE2, and nitric oxide (NO) synthsesis by a selective cyclooxygenase-2 (COX-2) inhibitor, NS-398, restores blood pressure as a result of increased systemic and renal levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in endotoxemic rats. The aim of this study was to further investigate the effects of NS-398 on the changes in expression and/or activity of COX-2, cyctochrome P450 4A1 (CYP4A1), inducible NO synthase (iNOS), and peroxynitrite formation in serum, renal, cardiac, and/or vascular tissues of lipopolysaacharide (LPS)-treated rats. LPS (10 mg/kg, i.p.)-induced decrease in blood pressure was associated with increased protein levels of COX-2, iNOS, and nitrotyrosine in kidney, heart, thoracic aorta, and superior mesenteric artery. The activities of COX-2 and iNOS as well as levels of PGI2, PGE2, and nitrotyrosine were also increased in the systemic circulation and renal, cardiac, and vascular tissues of LPS-treated rats. In contrast, renal, cardiac, and vascular CYP4A1 protein expression as well as systemic and tissue levels of 20-HETE were decreased in endotoxemic rats. These effects of LPS, except COX-2 protein expression, were prevented by NS-398 (10 mg/kg, i.p.), given 1 h after injection of LPS. These data suggest that COX-2-derived vasodilator prostanoids, PGI2 and PGE2, produced during endotoxemia increase iNOS protein expression and activity as well as peroxynitrite formation resulting in decreased CYP4A1 protein expression and 20-HETE synthesis. Taken together, we concluded that an increase in 20-HETE levels associated with a decrease in the production of vasodilator prostanoids and NO participates in the effect of NS-398 to prevent hypotension in the rat model of septic shock.

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Increased Sensitivity of the Baroreceptor Reflex after Bacterial Endotoxin

Cited by 19 publications

References 9 publications

Endotoxemia causes central downregulation of sympathetic vasomotor tone in healthy humans

Endotoxemia causes central downregulation of sympathetic vasomotor tone in healthy humans

Infusion of Escherichia coli Lipopolysaccharide Toxin in Rats Produces an Early and Severe Impairment of Baroreflex Function in Absence of Blood Pressure Changes

NS-398 reverses hypotension in endotoxemic rats: Contribution of eicosanoids, NO, and peroxynitrite

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