Intrinsic chemosensitivity of rostral ventrolateral medullary sympathetic premotor neurons in the <i>in situ</i> arterially perfused preparation of rats

Koganezawa, Tadachika; Paton, Julian F. R.

doi:10.1113/expphysiol.2014.080069

Cited by 19 publications

(22 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In rodents, neurons in areas, including the nucleus tractus solitarius and rostral ventrolateral medulla, are directly sensitive to hypoxia and cause sympathoexcitation and augmented BP. 42,43 Moreover, Marina et al 13 showed that hypoxia-induced activation of the rostral ventrolateral medulla in spontaneously hypertensive rats could be supressed by adenosine triphosphate antagonists or a glycogenesis inhibitor. These data indicate that metabolic by-products, which are increased during hypoxemia, can activate the neurons directly controlling sympathetic outflow.…”

Section: Discussionmentioning

confidence: 99%

Is High Blood Pressure Self-Protection for the Brain?

Warnert

Rodrigues

Burchell

et al. 2016

Circulation Research

View full text Add to dashboard Cite

H igh blood pressure (BP) affects ≈25% of the world's population and is the largest single contributor to global mortality. 1 Hypertension represents a significant economic burden to public healthcare providers, where the global cost of nonoptimal BP is estimated to be US$370 billion (10% of healthcare expenditure). 2Remarkably, despite the availability of many pharmacological treatments, BP is poorly controlled with a recent report stating that only 53% of patients prescribed antihypertensive medication have BP controlled.3 This reflects the well-known heterogeneity of the syndrome, including epigenetic and inherited factors contributing to the unknown causes in 95% of patients. Despite the devastating consequences of hypertension (eg, stroke, kidney failure, coronary heart disease, and death 1,2 ), the mechanisms that lead to the onset of hypertension in humans are poorly understood. It is well established that elevated sympathetic nerve activity (SNA) contributes to the development of hypertension in most humans, [5][6][7] but what initiates this remains unclear. Experimental data from hypertensive rats and observations in postmortem human studies suggest that blood flow to the brain might be important in setting the operating level of SNA and, thus, systemic arterial pressure. Rationale: Data from animal models of hypertension indicate that high blood pressure may develop as a vital mechanism to maintain adequate blood flow to the brain. We propose that congenital vascular variants of the posterior cerebral circulation and cerebral hypoperfusion could partially explain the pathogenesis of essential hypertension, which remains enigmatic in 95% of patients.Objective: To evaluate the role of the cerebral circulation in the pathophysiology of hypertension. Methods and Results:We completed a series of retrospective and mechanistic case-control magnetic resonance imaging and physiological studies in normotensive and hypertensive humans (n=259). Interestingly, in humans with hypertension, we report a higher prevalence of congenital cerebrovascular variants; vertebral artery hypoplasia, and an incomplete posterior circle of Willis, which were coupled with increased cerebral vascular resistance, reduced cerebral blood flow, and a higher incidence of lacunar type infarcts. Causally, cerebral vascular resistance was elevated before the onset of hypertension and elevated sympathetic nerve activity (n=126). Interestingly, untreated hypertensive patients (n=20) had a cerebral blood flow similar to age-matched controls (n=28). However, participants receiving antihypertensive therapy (with blood pressure controlled below target levels) had reduced cerebral perfusion (n=19). Finally, elevated cerebral vascular resistance was a predictor of hypertension, suggesting that it may be a novel prognostic or diagnostic marker (n=126). Conclusions:

show abstract

Section: Discussionmentioning

confidence: 99%

Is High Blood Pressure Self-Protection for the Brain?

Warnert

Rodrigues

Burchell

et al. 2016

Circulation Research

View full text Add to dashboard Cite

show abstract

“…This region receives convergent input from RTN, from caudal NTS neurons that relay carotid body inputs, from serotonergic neurons and from the C1 adrenergic cells (Bochorishvili et al, 2012; Burke et al, 2014; Song et al, 2011). The C1 neurons are highly responsive to carotid body stimulation and brain hypoxemia (Guyenet, 2014; Koganezawa and Paton, 2014) and arousal from NREM sleep is reliably elicited by C1 cell activation (Burke et al, 2014). …”

Section: Chemoreflexes and Sleepmentioning

confidence: 99%

Neural Control of Breathing and CO2 Homeostasis

Guyenet

Bayliss

2015

Neuron

391

332

View full text Add to dashboard Cite

Summary Recent advances have clarified how the brain detects CO2 to regulate breathing (central respiratory chemoreception). These mechanisms are reviewed and their significance is presented in the general context of CO2/pH homeostasis through breathing. At rest, respiratory chemoreflexes initiated at peripheral and central sites mediate rapid stabilization of arterial PCO2 and pH. Specific brainstem neurons (e.g., retrotrapezoid nucleus, RTN; serotonergic) are activated by PCO2 and stimulate breathing. RTN neurons detect CO2 via intrinsic proton receptors (TASK-2, GPR4), synaptic input from peripheral chemoreceptors and signals from astrocytes. Respiratory chemoreflexes are arousal state-dependent whereas chemoreceptor stimulation produces arousal. When abnormal, these interactions lead to sleep-disordered breathing. During exercise, “central command” and reflexes from exercising muscles produce the breathing stimulation required to maintain arterial PCO2 and pH despite elevated metabolic activity. The neural circuits underlying central command and muscle afferent control of breathing remain elusive and represent a fertile area for future investigation.

show abstract

“…Experimental evidence shows that RVLM neurons have their firing frequency reduced by stimulation of baroreceptor afferent fibres, leading to sympathoinhibitory and hypotensive responses, indicating that the baroreflex activation inhibits the activity of the presympathetic neurons (Haselton & Guyenet, ; Pedrino et al . ; Koganezawa & Paton, ). Therefore, after removal of arterial baroreceptor afferents [sino‐aortic denervation (SAD)], sympathetic overactivity and hypertension are expected in rats (Krieger, ).…”

Section: Introductionmentioning

confidence: 99%

“…The sympathetic tonus regulating the vascular resistance, cardiac output and, consequently, arterial pressure is generated by bulbospinal sympathetic premotor neurons located in the rostral ventrolateral medulla (RVLM; Sun et al 1988;Guyenet, 2006). Experimental evidence shows that RVLM neurons have their firing frequency reduced by stimulation of baroreceptor afferent fibres, leading to sympathoinhibitory and hypotensive responses, indicating that the baroreflex activation inhibits the activity of the presympathetic neurons (Haselton & Guyenet, 1989;Pedrino et al 2013;Koganezawa & Paton, 2014). Therefore, after removal of arterial baroreceptor afferents [sino-aortic denervation (SAD)], sympathetic overactivity and hypertension are expected in rats (Krieger, 1964).…”

Section: Introductionmentioning

confidence: 99%

Changes in the inspiratory pattern contribute to modulate the sympathetic activity in sino‐aortic denervated rats

Amorim

Bonagamba

Souza

et al. 2017

Experimental Physiology

View full text Add to dashboard Cite

What is the central question of this study? Sino-aortic denervated (SAD) rats present normal levels of sympathetic activity and mean arterial pressure. However, neural mechanisms regulating the sympathetic activity in the absence of arterial baroreceptors remain unclear. Considering that respiration modulates the sympathetic activity, we hypothesize that changes in the respiratory network contribute to keep the sympathetic outflow in the normal range after removal of arterial baroreceptors. What is the main finding and its importance? Despite longer inspiration observed in SAD rats, the respiratory-sympathetic coupling is working within a normal range of variation. These findings suggest that in the absence of arterial baroreceptors the respiratory modulation of sympathetic activity is maintained within the normal range. The activity of presympathetic neurons is under respiratory modulation, and changes in the central respiratory network may impact on the baseline sympathetic activity and mean arterial pressure. It is well known that after removal of baroreceptor afferents [sino-aortic denervation (SAD)], rats present an unexpected normal level of mean arterial pressure. We hypothesized that changes in the respiratory pattern and in the respiratory modulation of the sympathetic activity contribute to keep the sympathetic outflow within a normal range of variation in the absence of arterial baroreceptors in rats. To study these mechanisms, we recorded perfusion pressure and the activities of phrenic and thoracic sympathetic nerves in male juvenile rats using the working heart-brainstem preparation. The time of inspiration significantly increased in SAD rats, and this change was not dependent on the carotid bodies or on the vagal afferents. However, no changes were observed in the perfusion pressure or in the baseline thoracic sympathetic nerves in all phases of the respiratory cycle in SAD rats. Our data show that despite longer inspiratory activity, the baseline sympathetic activity is maintained at a normal level in SAD rats. These findings indicate that the respiratory-sympathetic coupling is normal after SAD and suggest that the respiratory modulation of sympathetic activity is maintained within the normal range after the removal of arterial baroreceptors.

show abstract

Intrinsic chemosensitivity of rostral ventrolateral medullary sympathetic premotor neurons in the in situ arterially perfused preparation of rats

Cited by 19 publications

References 55 publications

Is High Blood Pressure Self-Protection for the Brain?

Is High Blood Pressure Self-Protection for the Brain?

Neural Control of Breathing and CO2 Homeostasis

Changes in the inspiratory pattern contribute to modulate the sympathetic activity in sino‐aortic denervated rats

Contact Info

Product

Resources

About