-
Experimental and Therapeutic Medicine Feb 2018The protective mechanisms for liver preservation associated with hypothermic machine perfusion (HMP) remain unclear. However, the lack of a common and portable HMP...
The protective mechanisms for liver preservation associated with hypothermic machine perfusion (HMP) remain unclear. However, the lack of a common and portable HMP system for rat livers limits the study of HMP. The present study aimed to develop a novel, modified HMP system using a LifePort Kidney Transporter for preserving rat livers. A simple 'Y' shunt combined with a pressoreceptor for flow and pressure regulation was adapted to perfuse rat livers via the portal vein continuously using a LifePort Kidney Transporter under its 'prime mode' setting. An electronic scale was installed under the liver container to calculate the portal inflow according to the association with weight, density and volume of the perfusate. A total of 10 rat livers underwent 6 h of HMP using histidine-tryptophan-ketoglutarate solution enriched with acridine orange (AO) and propidium iodide (PI). The perfusion status of HMP was assessed by comparison of AO+PI-positive cell count in core region (CR) and peripheral region (PR) of rat liver under fluorescence microscopy. The dynamics (inflow, pressure and intrahepatic resistance of perfusion) were assessed to identify whether this system met the demands for HMP of rat livers. Biochemical [alanine transaminase (ALT), lactate dehydrogenase (LDH) and endothelin levels] and histological parameters (sinusoidal dilatation, endothelial cell detachment and vacuolization) were measured to determine cellular damage associated with HMP. No significant difference was observed between the CR and PR according to the comparison of the AO+PI-positive cell count, which indicated that complete perfusion was achieved. Intrahepatic resistance significantly decreased during the initial 3 h of HMP (P<0.01), but remained stable during the final 3 h. ALT and LDH levels significantly increased over the 6 h HMP duration: ALT (0 h, 42.67±5.81 U/l; 3 h, 90.67±6.74 U/l; 6 h, 164.33±7.31 U/l; P<0.01) and LDH (0 h, 492.90±90.20 U/l; 3 h, 973.53±97.4; 6 h, 1,843.40±85.78 U/l; P<0.01) However, the levels of endothelin and oxygen consumption were constant throughout HMP. Furthermore, histological analysis indicated sinusoidal dilation was significantly increased in the post-HMP group compared with the pre-HMP group (P<0.01); however, no other significant differences were observed. Combined with the results of ATP test (640.64±29.46 nmol/l) and bile production (4.88±0.69 µl/h/g of liver) at the end of HMP, the present results demonstrated minimal cellular injury associated with HMP while retaining the dependability and portability of the LifePort Kidney Transporter, which suggests the modified HMP system met the demands required and may be suitable for rat liver preservation.
PubMed: 29434725
DOI: 10.3892/etm.2017.5587 -
The Indian Journal of Medical Research Aug 2018Although insulin resistance (IR) is a known complication in obesity, the physiological mechanisms linking IR with cardiometabolic risks in obesity have not been well...
BACKGROUND & OBJECTIVES
Although insulin resistance (IR) is a known complication in obesity, the physiological mechanisms linking IR with cardiometabolic risks in obesity have not been well studied. This study was conducted to assess the difference in cardiovascular (CV) risk profile in IR and non-IR (NIR) conditions, and contribution of IR to cardiometabolic risks in pre-obese and obese individuals.
METHODS
Basal CV, blood pressure variability, autonomic function test and cardiometabolic parameters were recorded in pre-obese (n=86) and obese (n=77) individuals during 2012 and 2015. The association of altered cardiometabolic parameters with homeostatic model for IR (HOMA-IR) in pre-obese and obese groups and with baroreceptor sensitivity (BRS) in IR and NIR groups was calculated by appropriate statistical analysis.
RESULTS
Decreased BRS, a known CV risk and cardiometabolic parameters were significant in IR (pre-obese and obese) group compared to the NIR group. Sympathovagal imbalance in the form of increased sympathetic and decreased parasympathetic activities was observed in individuals with IR. There was no significant difference in the level of independent contribution of HOMA-IR to cardiometabolic parameters in pre-obese and obese groups. Adiponectin and inflammatory markers had an independent contribution to BRS in IR group.
INTERPRETATION & CONCLUSIONS
Findings of the present study demonstrated that the intensity of cardiometabolic derangements and CV risk were comparable between IR, pre-obese and obese individuals. Pro-inflammatory state, dyslipidaemia and hypoadiponectinaemia might contribute to CV risk in these individuals with IR. IR could possibly be the link between altered metabolic profile and increased CV risks in these individuals independent of the adiposity status.
Topics: Adult; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Dyslipidemias; Female; Humans; Insulin Resistance; Lipids; Male; Metabolic Diseases; Obesity; Pressoreceptors; Risk Factors
PubMed: 30381538
DOI: 10.4103/ijmr.IJMR_1751_16 -
Digestion 2020Transient receptor potential vanilloid 4 (TRPV4) is activated by stretch (mechanical), warm temperature, some epoxyeicosatrienoic acids, and lipopolysaccharide. TRPV4 is... (Review)
Review
Transient Receptor Potential Vanilloid 4 Regulation of Adenosine Triphosphate Release by the Adenosine Triphosphate Transporter Vesicular Nucleotide Transporter, a Novel Therapeutic Target for Gastrointestinal Baroreception and Chronic Inflammation.
BACKGROUND
Transient receptor potential vanilloid 4 (TRPV4) is activated by stretch (mechanical), warm temperature, some epoxyeicosatrienoic acids, and lipopolysaccharide. TRPV4 is expressed throughout the gastrointestinal epithelia and its activation induces adenosine triphosphate (ATP) exocytosis that is involved in visceral hypersensitivity. As an ATP transporter, vesicular nucleotide transporter (VNUT) mediates ATP storage in secretory vesicles and ATP release via exocytosis upon stimulation.
SUMMARY
TRPV4 is sensitized under inflammatory conditions by a variety of factors, including proteases and serotonin, whereas methylation-dependent silencing of TRPV4 expression is associated with various pathophysiological conditions. Gastrointestinal epithelia also release ATP in response to hypo-osmolality or acid through molecular mechanisms that remain unclear. These synergistically released ATP could be involved in visceral hypersensitivity. Low concentrations of the first generation bisphosphate, clodronate, were recently reported to inhibit VNUT activity and thus clodronate may be a safe and potent therapeutic option to treat visceral pain. Key Messages: This review focuses on: (1) ATP and TRPV4 activities in gastrointestinal epithelia; (2) factors that could modulate TRPV4 activity in gastrointestinal epithelia; and (3) the inhibition of VNUT as a potential novel therapeutic strategy for functional gastrointestinal disorders.
Topics: Abdominal Pain; Adenosine Triphosphate; Analgesics; Animals; Chronic Disease; Clodronic Acid; Gastrointestinal Tract; Humans; Inflammation; Mice; Mucous Membrane; Nucleotide Transport Proteins; Pressoreceptors; Receptors, Purinergic P2; TRPV Cation Channels
PubMed: 31770754
DOI: 10.1159/000504021 -
Journal of Neurophysiology Sep 2019Baroreceptors play a pivotal role in the regulation of blood pressure through moment to moment sensing of arterial blood pressure and providing information to the...
Baroreceptors play a pivotal role in the regulation of blood pressure through moment to moment sensing of arterial blood pressure and providing information to the central nervous system to make autonomic adjustments to maintain appropriate tissue perfusion. A recent publication by Zeng and colleagues (Zeng WZ, Marshall KL, Min S, Daou I, Chapleau MW, Abboud FM, Liberles SD, 362: 464-467, 2018) suggests the mechanosensitive ion channels Piezo1 and Piezo2 represent the cellular mechanism by which baroreceptor nerve endings sense changes in arterial blood pressure. However, before Piezo1 and Piezo2 are accepted as the sensor of baroreceptors, the question must be asked of what criteria are necessary to establish this and how well the report of Zeng and colleagues (Zeng WZ, Marshall KL, Min S, Daou I, Chapleau MW, Abboud FM, Liberles SD, 362: 464-467, 2018) satisfies these criteria. We briefly review baroreceptor function, outline criteria that a putative neuronal sensor of blood pressure must satisfy, and discuss whether the recent findings of Zeng and colleagues suitably meet these criteria. Despite the provocative hypothesis, there are significant concerns regarding the evidence supporting a role of Piezo1/Piezo2 in arterial baroreceptor function.
Topics: Animals; Autonomic Nervous System; Baroreflex; Blood Pressure; Humans; Ion Channels; Pressoreceptors
PubMed: 31314636
DOI: 10.1152/jn.00315.2019 -
Experimental Physiology Aug 2014Although drug treatment of human hypertension has greatly improved, there is renewed interest in non-drug methods of blood pressure reduction. Animal experiments have... (Review)
Review
Although drug treatment of human hypertension has greatly improved, there is renewed interest in non-drug methods of blood pressure reduction. Animal experiments have now shown that arterial baroreflexes do control long-term blood pressure levels, particularly by nervously mediated renal excretion of sodium and water. This Paton Lecture provides a review of the historical development of knowledge of peripheral circulatory control in order to supplement prior Paton Lectures concerned with cerebral cortical and other areas of influence. I also discuss how improved understanding of nervous control of the circulation has led to current methods of non-drug blood pressure control in man by implanted carotid baroreceptor pacemakers or by renal denervation. Finally, the role of other therapy, particularly listening to music, is reviewed.
Topics: Animals; Arteries; Baroreflex; Blood Pressure; Cardiovascular System; Cerebral Cortex; Humans; Hypertension; Pressoreceptors
PubMed: 24986973
DOI: 10.1113/expphysiol.2014.079434 -
The Journal of Physiological Sciences :... May 2018Although the amygdala is known as a negative emotion center for coordinating defensive behaviors, its functions in autonomic control remain unclear. To resolve this...
Although the amygdala is known as a negative emotion center for coordinating defensive behaviors, its functions in autonomic control remain unclear. To resolve this issue, we examined effects on cardiovascular responses induced by stimulation and lesions of the amygdala in anesthetized and free-moving rats. Electrical microstimulation of the central nucleus of the amygdala (CeA) induced a gradual increase in arterial pressure (AP) and heart rate (HR), whereas stimulation of adjacent nuclei evoked a phasic AP decrease. The gain of the baroreceptor reflex was not altered by CeA stimulation, suggesting that CeA activity increases both AP and HR by resetting baroreceptor reflex function. Disinhibition of GABAergic input by amygdalar microinjection of the GABA receptor antagonist induced robust increases in AP and HR. Furthermore, bilateral electrolytic lesions of CeA evoked consistent AP increases over the light/dark cycle. These results suggest that the amygdala exerts 'bidirectional' autonomic control over the cardiovascular system.
Topics: Amygdala; Animals; Arterial Pressure; Baroreflex; Cardiovascular System; Electric Stimulation; GABA-A Receptor Antagonists; Heart Rate; Male; Pressoreceptors; Rats; Rats, Wistar; Reflex
PubMed: 28111704
DOI: 10.1007/s12576-017-0523-2 -
Scientific Reports Jan 2021Head-down bed rest (HDBR) has previously been shown to alter cerebrovascular and autonomic control. Previous work found that sustained HDBR (≥ 20 days) attenuates... (Randomized Controlled Trial)
Randomized Controlled Trial
Head-down bed rest (HDBR) has previously been shown to alter cerebrovascular and autonomic control. Previous work found that sustained HDBR (≥ 20 days) attenuates the hypercapnic ventilatory response (HCVR); however, little is known about shorter-term effects of HDBR nor the influence of HDBR on the hypoxic ventilatory response (HVR). We investigated the effect of 4-h HDBR on HCVR and HVR and hypothesized attenuated ventilatory responses due to greater carotid and brain blood flow. Cardiorespiratory responses of young men (n = 11) and women (n = 3) to 5% CO or 10% O before and after 4-h HDBR were examined. HDBR resulted in lower HR, lower cardiac output index, lower common carotid artery flow, higher SpO, and higher pulse wave velocity. After HDBR, tidal volume and ventilation responses to 5% CO were enhanced (all P < 0.05), yet no other changes in cardiorespiratory variables were evident. There was no influence of HDBR on the cardiorespiratory responses to hypoxia (all P > 0.05). Short-duration HDBR does not alter the HVR, yet enhances the HCVR, which we hypothesize is a consequence of cephalic CO accumulation from cerebral congestion.
Topics: Bed Rest; Blood Pressure; Female; Head-Down Tilt; Heart Rate; Humans; Hypercapnia; Hypoxia; Male; Middle Cerebral Artery; Pressoreceptors; Respiration; Stroke Volume; Tidal Volume; Vascular Resistance; Young Adult
PubMed: 33495489
DOI: 10.1038/s41598-021-81837-w -
American Journal of Physiology. Heart... Aug 2020Changes in the arterial baroreflex arc contribute to elevated sympathetic outflow and altered reflex control of blood pressure with human aging. Using ultrasound and... (Comparative Study)
Comparative Study
Changes in the arterial baroreflex arc contribute to elevated sympathetic outflow and altered reflex control of blood pressure with human aging. Using ultrasound and sympathetic microneurography (muscle sympathetic nerve activity, MSNA) we investigated the relationships between aortic and carotid artery wall tension (indices of baroreceptor activation) and the vascular sympathetic baroreflex operating point (OP; MSNA burst incidence) in healthy, normotensive young ( = 27, 23 ± 3 yr) and middle-aged men ( = 22, 55 ± 4 yr). In young men, the OP was positively related to the magnitude and rate of unloading and time spent unloaded in the aortic artery ( = 0.56, 0.65, and 0.51, = 0.02, 0.003, and 0.03), but not related to the magnitude or rate of unloading or time spent unloaded in the carotid artery ( = -0.32, -0.07, and 0.06, = 0.25, 0.81, and 0.85). In contrast, in middle-aged men, the OP was not related to either the magnitude or rate of unloading or time spent unloaded in the aortic ( = 0.22, 0.21, and 0.27, = 0.41, 0.43, and 0.31) or carotid artery ( = 0.06, 0.28, and -0.01; = 0.48, 0.25, and 0.98). In conclusion, in young men, aortic unloading mechanics may play a role in determining the vascular sympathetic baroreflex OP. In contrast, in middle-aged men, barosensory vessel unloading mechanics do not appear to determine the vascular sympathetic baroreflex OP and, therefore, do not contribute to age-related arterial baroreflex resetting and increased resting MSNA. We assessed the influence of barosensory vessel mechanics (magnitude and rate of unloading and time spent unloaded) as a surrogate for baroreceptor unloading. In young men, aortic unloading mechanics are important in regulating the operating point of the vascular sympathetic baroreflex, whereas in middle-aged men, these arterial mechanics do not influence this operating point. The age-related increase in resting muscle sympathetic nerve activity does not appear to be driven by altered baroreceptor input from stiffer barosensory vessels.
Topics: Adult; Age Factors; Aging; Aorta; Arterial Pressure; Baroreflex; Carotid Arteries; Heart Rate; Homeostasis; Humans; Male; Middle Aged; Muscle, Skeletal; Pressoreceptors; Time Factors; Ultrasonography; Young Adult
PubMed: 32648822
DOI: 10.1152/ajpheart.00265.2020 -
Journal of Hypertension Jul 2023The blood pressure (BP) regulatory impact of the arterial baroreflex has been well established in health and disease. Under normotensive conditions, we have previously...
BACKGROUND
The blood pressure (BP) regulatory impact of the arterial baroreflex has been well established in health and disease. Under normotensive conditions, we have previously demonstrated functional differences in the central processing of the left versus right aortic baroreceptor afferent input. However, it is unknown if lateralization in aortic baroreflex function remains evident during hypertension.
METHOD
We therefore, investigated the effects of laterality on the expression of baroreflex-driven cardiovascular reflexes in a genetic model of essential hypertension, the spontaneously hypertensive rat (SHR). Anesthetized male SHRs (total n = 9) were instrumented for left, right, and bilateral aortic depressor nerve (ADN) stimulation (1-40 Hz, 0.2 ms, and 0.4 mA for 20 s) and measurement of mean arterial pressure (MAP), heart rate (HR), mesenteric vascular resistance (MVR), and femoral vascular resistance (FVR).
RESULTS
Left right, and bilateral ADN stimulation evoked frequency-dependent decreases in MAP, HR, MVR, and FVR. Left and bilateral ADN stimulation evoked greater reflex reductions in MAP, HR, MVR, and FVR compared with right-sided stimulation. Reflex bradycardia to bilateral stimulation was larger relative to both left-sided and right-sided stimulation. Reflex depressor and vascular resistance responses to bilateral stimulation mimicked those of the left-sided stimulation. These data indicate a left-side dominance in the central integration of aortic baroreceptor afferent input. Furthermore, reflex summation due to bilateral stimulation is only evident on the reflex bradycardic response, and does not drive further reductions in BP, suggesting that reflex depressor responses in the SHRs are primarily driven by changes in vascular resistance.
CONCLUSION
Together, these results indicate that lateralization in aortic baroreflex function is not only evident under normotensive conditions but also extends to hypertensive conditions.
Topics: Rats; Animals; Male; Rats, Inbred SHR; Pressoreceptors; Electric Stimulation; Blood Pressure; Baroreflex; Hypertension; Heart Rate; Aorta
PubMed: 37074354
DOI: 10.1097/HJH.0000000000003448 -
Experimental Physiology May 2021Cardio-ventilatory coupling refers to the onset of inspiration occurring at a preferential latency following the last heartbeat (HB) in expiration. According to the...
NEW FINDINGS
Cardio-ventilatory coupling refers to the onset of inspiration occurring at a preferential latency following the last heartbeat (HB) in expiration. According to the cardiac-trigger hypothesis, the pulse pressure initiates an inspiration via baroreceptor activation. However, the central neural substrate mediating this coupling remains undefined. Using a combination of animal data, human data and mathematical modelling, this study tests the hypothesis that the HB, by way of pulsatile baroreflex activation, controls the initiation of inspiration that occurs through a rapid neural activation loop from the carotid baroreceptors to Bötzinger complex expiratory neurons.
ABSTRACT
Cardio-ventilatory coupling refers to a heartbeat (HB) occurring at a preferred latency prior to the next breath. We hypothesized that the pressure pulse generated by a HB activates baroreceptors that modulate brainstem expiratory neuronal activity and delay the initiation of inspiration. In supine male subjects, we recorded ventilation, electrocardiogram and blood pressure during 20-min epochs of baseline, slow-deep breathing and recovery. In in situ rodent preparations, we recorded brainstem activity in response to pulses of perfusion pressure. We applied a well-established respiratory network model to interpret these data. In humans, the latency between a HB and onset of inspiration was consistent across different breathing patterns. In in situ preparations, a transient pressure pulse during expiration activated a subpopulation of expiratory neurons normally active during post-inspiration, thus delaying the next inspiration. In the model, baroreceptor input to post-inspiratory neurons accounted for the effect. These studies are consistent with baroreflex activation modulating respiration through a pauci-synaptic circuit from baroreceptors to onset of inspiration.
Topics: Animals; Baroreflex; Blood Pressure; Heart Rate; Humans; Male; Pressoreceptors; Respiration
PubMed: 33749038
DOI: 10.1113/EP089365