Descending pathways from the superior colliculus mediating autonomic and respiratory effects associated with orienting behaviour.

The ability to discriminate competing external stimuli and initiate contextually appropriate behaviours is a key brain function. Neurons in the deep superior colliculus (dSC) integrate multisensory inputs and activate descending projections to premotor pathways responsible for orienting, attention and defence, behaviours which involve adjustments to respiratory and cardiovascular parameters. However, the neural pathways that subserve the physiological components of orienting are poorly understood.

Upregulated Angiotensin Ia Receptors in the Hypothalamic Paraventricular Nucleus Sensitize Neuroendocrine Vasopressin Release and Blood Pressure in a Rodent Model of Polycystic Kidney Disease.

Introduction: Angiotensin (Ang) II signalling in the hypothalamic paraventricular nucleus (PVN) via Ang type-1a receptors (AT1R) regulates vasopressin release and sympathetic nerve activity - two effectors of blood pressure regulation. We determined the cellular expression and function of AT1R in the PVN of a rodent model of polycystic kidney disease (PKD), the Lewis polycystic kidney (LPK) rat, to evaluate its contribution to blood pressure regulation and augmented vasopressin release in PKD.

Methods: PVN AT1R gene expression was quantified with fluorescent in situ hybridization in LPK and control rats.

Do catecholaminergic TrkC DRG neurons represent a class of cardiovascular enteroceptor?

In a recent issue of Cell Reports, Morelli et al. (2021) identify a subpopulation of mechanosensitive peripheral sensory neurons that coexpress tyrosine hydroxylase (TH) and tropomyosin receptor kinase C (TrkC) and innervate cutaneous arterioles. They show that activation of TrkC sensory neurons causes cutaneous vasoconstriction and, most remarkably, that their lesion is associated with sudden death of an undetermined cause, preceded by a progressive drop in blood pressure, and conclude that TrkC TH neurons represent a baroreceptor class of homeostatic enteroceptor.

Renal denervation does not affect hypertension or the renin-angiotensin system in a rodent model of juvenile-onset polycystic kidney disease: clinical implications.

We examined the effect of total and afferent renal denervation (RDN) on hypertension and the renin-angiotensin system (RAS) in a rodent model of juvenile-onset polycystic kidney disease (PKD). Lewis Polycystic Kidney (LPK) and control rats received total, afferent or sham RDN by periaxonal application of phenol, capsaicin or normal saline, respectively, and were monitored for 4-weeks. Afferent RDN did not affect systolic blood pressure (SBP) determined by radiotelemetry in either strain (n = 19) while total RDN significantly reduced SBP in Lewis rats 4-weeks post-denervation (total vs.

Relationship between sex and cardiovascular mortality in chronic kidney disease: A systematic review and meta-analysis.

Chronic kidney disease (CKD) is a significant health challenge associated with high cardiovascular mortality risk. Historically, cardiovascular mortality risk has been found to higher in men than women in the general population. However, recent research has highlighted that this risk may be similar or even higher in women than men in the CKD population.

Augmented Respiratory-Sympathetic Coupling and Hemodynamic Response to Acute Mild Hypoxia in Female Rodents With Chronic Kidney Disease.

Carotid body feedback and hypoxia may serve to enhance respiratory-sympathetic nerve coupling (respSNA) and act as a driver of increased blood pressure. Using the Lewis polycystic kidney (LPK) rat model of chronic kidney disease, we examined respSNA in adult female rodents with CKD and their response to acute hypoxia or hypercapnia compared to Lewis control animals. Under urethane anesthesia, phrenic nerve activity, splanchnic sympathetic nerve activity (sSNA), and renal sympathetic nerve activity (rSNA) were recorded under baseline conditions and during mild hypoxic or hypercapnic challenges.

The subfornical organ drives hypertension in polycystic kidney disease via the hypothalamic paraventricular nucleus.

Aims: Hypertension is a prevalent yet poorly understood feature of polycystic kidney disease. Previously, we demonstrated that increased glutamatergic neurotransmission within the hypothalamic paraventricular nucleus produces hypertension in the Lewis Polycystic Kidney (LPK) rat model of polycystic kidney disease. Here, we tested the hypothesis that augmented glutamatergic drive to the paraventricular nucleus in Lewis polycystic kidney rats originates from the forebrain lamina terminalis, a sensory structure that relays blood-borne information throughout the brain.

Neurons in the Intermediate Reticular Nucleus Coordinate Postinspiratory Activity, Swallowing, and Respiratory-Sympathetic Coupling in the Rat.

Breathing results from sequential recruitment of muscles in the expiratory, inspiratory, and postinspiratory (post-I) phases of the respiratory cycle. Here we investigate whether neurons in the medullary intermediate reticular nucleus (IRt) are components of a central pattern generator (CPG) that generates post-I activity in laryngeal adductors and vasomotor sympathetic nerves and interacts with other members of the central respiratory network to terminate inspiration. We first identified the region of the (male) rat IRt that contains the highest density of lightly cholinergic neurons, many of which are glutamatergic, which aligns well with the putative postinspiratory complex in the mouse (Anderson et al.

Respiratory sympathetic modulation is augmented in chronic kidney disease.

Respiratory modulation of sympathetic nerve activity (respSNA) was studied in a hypertensive rodent model of chronic kidney disease (CKD) using Lewis Polycystic Kidney (LPK) rats and Lewis controls. In adult animals under in vivo anaesthetised conditions (n = 8-10/strain), respiratory modulation of splanchnic and renal nerve activity was compared under control conditions, and during peripheral (hypoxia), and central, chemoreceptor (hypercapnia) challenge. RespSNA was increased in the LPK vs.

Osmoregulation in Polycystic Kidney Disease: Relationship with Cystogenesis and Hypertension.

Polycystic kidney disease (PKD) is a group of monogenetic conditions characterised by the progressive accumulation of multiple renal cysts and hypertension. One of the earliest features of PKD is a reduction in urinary concentrating capacity that impairs extracellular fluid conservation. Urinary concentrating impairment predisposes PKD patients to periods of hypohydration when fluid loss is not adequately compensated by fluid intake.

Increased arterial stiffness does not respond to renal denervation in an animal model of secondary hypertension.

Renal denervation is a novel device based therapy promoted to reduce high blood pressure. We examined the impact of renal denervation on systolic blood pressure, renal function, and arterial stiffness in the Lewis Polycystic Kidney disease (LPK) rodent model of kidney disease. Animals were subjected to bilateral renal denervation or sham surgeries at age 6 and 12 weeks.

Effect of anaesthetic and choice of neuromuscular blocker on vagal control of heart rate under laboratory animal experimental conditions.

Neuromuscular-blocking agents are commonly used in laboratory animal research settings. Due to actions of cholinergic receptors at locations other than the motor end-plate, these agents have a strong propensity to modulate autonomic outflow and may therefore not be desirable in studies examining autonomic function. This study aimed to compare the effect of two non-depolarizing neuromuscular-blocking agents, pancuronium and cisatracurium, on blood pressure, heart rate and non-invasive indices of autonomic function (heart rate variability, systolic blood pressure variability and baroreflex sensitivity) under two different types of anaesthesia in Lewis rats.

Chronic kidney disease impairs renal nerve and haemodynamic reflex responses to vagal afferent input through a central mechanism.

We investigated age- and sex-related changes in reflex renal sympathetic nerve activity (RSNA) and haemodynamic responses to vagal afferent stimulation in a rodent model of chronic kidney disease (CKD). Using anaesthetised juvenile (7-8weeks) and adult (12-13weeks) Lewis Polycystic Kidney (LPK) and Lewis control rats of either sex (n=63 total), reflex changes in RSNA, heart rate (HR) and mean arterial pressure (MAP) to vagal afferent stimulation (5-s train, 4.0V, 2.

Direct conscious telemetry recordings demonstrate increased renal sympathetic nerve activity in rats with chronic kidney disease.

Chronic kidney disease (CKD) is associated with sympathetic hyperactivity and impaired blood pressure control reflex responses, yet direct evidence demonstrating these features of autonomic dysfunction in conscious animals is still lacking. Here we measured renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) using telemetry-based recordings in a rat model of CKD, the Lewis Polycystic Kidney (LPK) rat, and assessed responses to chemoreflex activation and acute stress. Male LPK and Lewis control animals (total n = 16) were instrumented for telemetric recording of RSNA and MAP.

Abnormal central control underlies impaired baroreflex control of heart rate and sympathetic nerve activity in female Lewis polycystic kidney rats.

Objective: Why baroreflex dysfunction occurs in females with chronic kidney disease is unknown. We therefore aimed to examine whether temporal changes in baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) occur in female Lewis polycystic kidney (LPK) rats and whether this is associated with any changes in afferent, central or efferent processing of the reflex pathway.

Method: Using urethane-anaesthetized juvenile and adult LPK and Lewis control rats (n = 40), baroreflex-mediated changes in HR, RSNA and aortic depressor nerve activity (ADNA) were examined.

The effect of losartan on differential reflex control of sympathetic nerve activity in chronic kidney disease.

Background: The effect of angiotensin II type I receptor (AT1R) inhibition on the pattern of reflex sympathetic nerve activity (SNA) to multiple target organs in the Lewis polycystic kidney (LPK) rat model of chronic kidney disease was determined.

Methods: Mean arterial pressure (MAP), splanchnic SNA (sSNA), renal SNA (rSNA) and lumbar SNA (lSNA) were recorded in urethane-anaesthetized LPK and Lewis controls (total n = 39). Baroreflex, peripheral and central chemoreflex, and somatosensory reflex control of SNA (evoked by phenylephrine/sodium nitroprusside infusion, 10% O2 in N2 or 100% N2 ventilation, 5% CO2 ventilation and sciatic nerve stimulation, respectively) were determined before and after administration of losartan (AT1R antagonist 3 mg/kg, intravenous).

Sympathetic overactivity prevails over the vascular amplifier phenomena in a chronic kidney disease rat model of hypertension.

We examined whether increased sympathetic nerve activity (SNA) accounts for enhanced depressor responses to ganglionic blockade in the Lewis polycystic kidney (LPK) model of chronic kidney disease (CKD) or whether it reflects increased vascular responses to vasodilation (vascular amplifier). Under urethane anesthesia, depressor responses to ganglionic blockade (hexamethonium, 0.5-40 mg/kg i.

Differential contribution of afferent and central pathways to the development of baroreflex dysfunction in chronic kidney disease.

The effects of chronic kidney disease on baroreflex control of renal sympathetic nerve activity (RSNA) and deficits in afferent and central components of the baroreflex were studied in juvenile and adult male Lewis Polycystic Kidney (LPK) and control Lewis rats under anesthesia (n=35). Blood pressure (BP), heart rate (HR), aortic depressor nerve activity (ADNA), and RSNA were determined after pharmacological manipulation of BP. Responses to ADN stimulation (4.

Temporal development of baroreceptor dysfunction in a rodent model of chronic kidney disease.

Altered autonomic control of the cardiovascular system in chronic kidney disease (CKD) contributes to an increased risk of cardiovascular events. The aim of the present study was to determine whether and when autonomic dysfunction occurs in a conscious, telemetered, rodent model of CKD. In Lewis polycystic kidney (LPK; n = 8) and Lewis (n = 8) rats, blood pressure (BP), heart rate (HR), HR variability (HRV), systolic BP variability (SBPV) and baroreflex sensitivity (BRS) were determined from 10 to 16 weeks of age.

Prognostic indicators of cardiovascular risk in renal disease.

Although the annual mortality rate for end-stage renal disease (ESRD) is decreasing, likely due to an increase in kidney transplantation rate, the survival probability for ESRD patients from day one of dialysis has not changed, and is still poor with a 5-year survival rate of approximately 34%. This is contributed to by a high prevalence of cardiovascular disease, which is the leading cause of death in ESRD patients. In order to improve survival outcomes, patients at high risk of cardiovascular related mortality need to be identified.

Angiotensin-converting enzyme inhibitor limits pulse-wave velocity and aortic calcification in a rat model of cystic renal disease.

The effect of angiotensin-converting enzyme inhibition on function and structure of the aorta was studied in the Lewis polycystic kidney (LPK) rat model of cystic renal disease and Lewis controls. Pulse-wave velocity (PWV) was recorded under urethane anesthesia (1.3 g/kg ip) in mixed-sex animals aged 6 and 12 wk and in 12-wk-old animals treated with perindopril (3 mg·kg(-1)·day(-1) po) from age 6-12 wk.

Aortic stiffness is associated with vascular calcification and remodeling in a chronic kidney disease rat model.

Increased aortic pulse-wave velocity (PWV) reflects increased arterial stiffness and is a strong predictor of cardiovascular risk in chronic kidney disease (CKD). We examined functional and structural correlations among PWV, aortic calcification, and vascular remodeling in a rodent model of CKD, the Lewis polycystic kidney (LPK) rat. Hemodynamic parameters and beat-to-beat aortic PWV were recorded in urethane-anesthetized animals [12-wk-old hypertensive female LPK rats (n = 5)] before the onset of end-stage renal disease and their age- and sex-matched normotensive controls (Lewis, n = 6).