Cellular and Molecular Mechanisms Underlying Arterial Baroreceptor Remodeling in Cardiovascular Diseases and Diabetes / 神经科学通报·英文版

Clinical trials and animal experimental studies have demonstrated an association of arterial baroreflex impairment with the prognosis and mortality of cardiovascular diseases and diabetes. As a primary part of the arterial baroreflex arc, the pressure sensitivity of arterial baroreceptors is blunted and involved in arterial baroreflex dysfunction in cardiovascular diseases and diabetes. Changes in the arterial vascular walls, mechanosensitive ion channels, and voltage-gated ion channels contribute to the attenuation of arterial baroreceptor sensitivity. Some endogenous substances (such as angiotensin II and superoxide anion) can modulate these morphological and functional alterations through intracellular signaling pathways in impaired arterial baroreceptors. Arterial baroreceptors can be considered as a potential therapeutic target to improve the prognosis of patients with cardiovascular diseases and diabetes.

Contribution of insulin resistance to decreased baroreceptor sensitivity & cardiometabolic risks in pre-obesity & obesity

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.

Paciente con hipertensión arterial y deterioro de su clase funcional secundarios al síndrome de taquicardia postural ortostática / Patient with arterial hypertension and functional class deterioration secondary to postural orthostatic tachycardia syndrome

Resumen La hipertensión ortostática ha sido un diagnóstico elusivo en la práctica clínica por la falta de estudio respecto a su fisiopatología y epidemiología. De esa manera, el abordaje clínico no ha sido expedito para su diagnóstico y tratamiento, así que las causas primarias pueden pasar inadvertidas y sin tratamiento. Se expone el caso clínico de una paciente latina, con hipertensión arterial sumada a deterioro de su clase funcional, a quien se le descartaron otras causas secundarias de hipertensión, y se diagnosticó, mediante estudio hemodinámico y autonómico, síndrome de taquicardia ortostática postural y compromiso del retorno venoso como causa primaria. Este reporte de caso pretende ilustrar respecto a esta causa infrecuente de hipertensión secundaria.

Abstract Orthostatic hypertension has been an elusive diagnosis in clinical practice due to the lack of research with regards to its pathophysiology and aetiology. Thus, clinical approach has not been unobstructed for its diagnosis and treatment, so the primary causes may go unnoticed and remain untreated. The clinical case of a Latin American patient with arterial hypertension associated to a deterioration of her functional class is reported. Secondary causes for hypertension were ruled out and, by means of a hemodynamic and autonomic study, she was diagnosed with postural orthostatic tachycardia syndrome and reduced venous return as the primary cause. This case report pretends to illustrate this rare case of secondary hypertension.

Neuropeptides in the posterodorsal medial amygdala modulate central cardiovascular reflex responses in awake male rats

The rat posterodorsal medial amygdala (MePD) links emotionally charged sensory stimuli to social behavior, and is part of the supramedullary control of the cardiovascular system. We studied the effects of microinjections of neuroactive peptides markedly found in the MePD, namely oxytocin (OT, 10 ng and 25 pg; n=6/group), somatostatin (SST, 1 and 0.05 μM; n=8 and 5, respectively), and angiotensin II (Ang II, 50 pmol and 50 fmol; n=7/group), on basal cardiovascular activity and on baroreflex- and chemoreflex-mediated responses in awake adult male rats. Power spectral and symbolic analyses were applied to pulse interval and systolic arterial pressure series to identify centrally mediated sympathetic/parasympathetic components in the heart rate variability (HRV) and arterial pressure variability (APV). No microinjected substance affected basal parameters. On the other hand, compared with the control data (saline, 0.3 µL; n=7), OT (10 ng) decreased mean AP (MAP50) after baroreflex stimulation and increased both the mean AP response after chemoreflex activation and the high-frequency component of the HRV. OT (25 pg) increased overall HRV but did not affect any parameter of the symbolic analysis. SST (1 μM) decreased MAP50, and SST (0.05 μM) enhanced the sympathovagal cardiac index. Both doses of SST increased HRV and its low-frequency component. Ang II (50 pmol) increased HRV and reduced the two unlike variations pattern of the symbolic analysis (P<0.05 in all cases). These results demonstrate neuropeptidergic actions in the MePD for both the increase in the range of the cardiovascular reflex responses and the involvement of the central sympathetic and parasympathetic systems on HRV and APV.

Analysis of the Baroreceptor and Vestibular Receptor Inputs in the Rostral Ventrolateral Medulla following Hypotension in Conscious Rats

Input signals originating from baroreceptors and vestibular receptors are integrated in the rostral ventrolateral medulla (RVLM) to maintain blood pressure during postural movement. The contribution of baroreceptors and vestibular receptors in the maintenance of blood pressure following hypotension were quantitatively analyzed by measuring phosphorylated extracellular regulated protein kinase (pERK) expression and glutamate release in the RVLM. The expression of pERK and glutamate release in the RVLM were measured in conscious rats that had undergone bilateral labyrinthectomy (BL) and/or sinoaortic denervation (SAD) following hypotension induced by a sodium nitroprusside (SNP) infusion. The expression of pERK was significantly increased in the RVLM in the control group following SNP infusion, and expression peaked 10 min after SNP infusion. The number of pERK positive neurons increased following SNP infusion in BL, SAD, and BL+SAD groups, although the increase was smaller than seen in the control group. The SAD group showed a relatively higher reduction in pERK expression when compared with the BL group. The level of glutamate release was significantly increased in the RVLM in control, BL, SAD groups following SNP infusion, and this peaked 10 min after SNP infusion. The SAD group showed a relatively higher reduction in glutamate release when compared with the BL group. These results suggest that the baroreceptors are more powerful in pERK expression and glutamate release in the RVLM following hypotension than the vestibular receptors, but the vestibular receptors still have an important role in the RVLM.

Static Magnetic Field Effect on Cardiovascular Regulation: A Review.

Mounting evidence suggests that environmental and occupational magnetic fields affect cardiovascular system. In this review, supported by original hemodynamic recordings - direct experimental evidence of the effect - static magnetic field (SMF) effects on arterial baroreflex cardiovascular control mechanism have been summarized. Local exposure of 120 - 350 mT SMF to sinocarotid baroreceptors in rabbits and healthy volunteers exerted a stimulatory effect on arterial baroreflex - normalized arterial blood pressure in hypertensive and hypotensive conditions, significantly increased microcirculation, heart rate variability, arterial baroreflex sensitivity and sodium nitroprusside (spontaneous nitric oxide donor) microcirculatory vasodilatory effect. The improvement of the vasodilator responsiveness to nitric oxide by baroreceptor stimulation suggested to be a new mechanism in baroreflex physiology with potential implementation in a spectrum of cardiovascular diseases where endothelial dysfunction and sympathovagal imbalance that results from a loss of baroreflex control over autonomic activity increases the risk of morbidity and mortality substantially. The modulation of the baroreflex-mediated autonomic cardiovascular control is a new concept for understanding environmental magnetic fields effect on cardiovascular system and an effective strategy to prevent their potential public health hazards.

Effect of Vestibulosympathetic Reflex and Baroreflex on Expression of pERK in the Nucleus Tractus Solitarius following Acute Hypotension in Conscious Rats

Control of blood pressure is maintained by the interaction between the arterial baroreflex and vestibulosympathetic reflex during postural changes. In this study, the contributions of vestibular receptors and baroreceptors to the maintenance of blood pressure following acute hypotension were compared in terms of phosphorylated extracellular regulated protein kinase (pERK) expression in the nucleus tractus solitaries (NTS). Expression of pERK in the NTS was measured in conscious rats that had undergone bilateral labyrinthectomy (BL) and/or sinoaortic denervation (SAD) 5, 10, 20, and 40 min following acute hypotension induced by sodium nitroprusside (SNP) infusion. Expression of pERK increased significantly in the NTS in the control group following SNP infusion, and the expression peaked at 10 min after SNP infusion. The number of pERK positive neurons increased following SNP infusion in BL, SAD, and BL+SAD groups, although the increase was smaller than in control group. The BL group showed a relatively higher reduction in pERK expression than the SAD group, and the pERK expression in the NTS was localized to the caudal portion of the nuclei in the BL and SAD groups. These results suggest that the vestibular receptors may play a key role in maintaining blood pressure following acute hypotension; thus, the vestibular system may contribute to compensate for orthostatic hypotension.

Additive Role of the Vestibular End Organ and Baroreceptors on the Regulation of Blood Pressure in Rats

Contribution of the vestibular end organ to regulation of arterial pressure was quantitatively compared with the role of baroreceptors in terms of baroreflex sensitivity and c-Fos protein expression in the rostral ventrolateral medulla (RVLM). Baroreflex sensitivity and c-Fos protein expression in the RVLM were measured in conscious rats that had undergone bilateral labyrinthectomy (BL) and/or baroreceptor unloading. BL attenuated baroreflex sensitivity during intravenous infusion of sodium nitroprusside (SNP), but did not significantly affect the sensitivity following infusion of phenylephrine (PE). Baroreflex sensitivity became positive following sinoaortic denervation (SAD) during infusion of PE and attenuated sensitivity during infusion of SNP. Baroreflex sensitivity also became positive following double ablation (BL+SAD) during infusion of PE, and attenuated sensitivity during infusion of SNP. c-Fos protein expression increased significantly in the RVLM in the sham group after SNP administration. However, the BL, SAD, and SAD+BL groups showed significant decreases in c-Fos protein expression compared with that in the sham group. The SAD group showed more reduced c-Fos protein expression than that in the BL group, and the SAD+BL group showed less expression than that in the SAD group. These results suggest that the vestibular system cooperates with baroreceptors to maintain arterial pressure during hypotension but that baroreceptors regulate arterial pressure during both hypotension and hypertension. Additionally, afferent signals for maintaining blood pressure from the vestibular end organs and the baroreceptors may be integrated in the RVLM.

Breve historia del reflejo barorreceptor: de Claude Bernard a Arthur C. Guyton. Ilustrada con algunos experimentos clásicos / A brief history of the baroreceptor reflex: From Claude Bernard to Arthur C. Guyton. Illustrated with some classical experiments

El reflejo barorreceptor es poco conocido por la mayoría de los médicos a pesar de que es fundamental en la estabilización de la presión arterial latido a latido y es crucial para la supervivencia. Su fascinante historia es brevemente revisada en este artículo. En 1852 Claude Bernard descubrió que los nervios simpáticos del cuello inervan los vasos sanguíneos de la piel. En 1932 Edgar Douglas Adrian demostró que los nervios simpáticos que inervan los vasos sanguíneos de la piel descargan en forma espontánea a una frecuencia de cuatro a seis por segundo y de esta forma encontró las bases fisiológicas del tono vasomotor. En el siglo XIX Ludwig Traube y Karl Constantine Ewald Hering descubrieron que la presión arterial fluctúa sincrónicamente con la respiración y Sigmund Mayer observó que también existían oscilaciones más lentas no relacionadas con la respiración. En 1921 Heinrich Ewald Hering mostró la existencia de barorreceptores de alta presión en los senos carotideos y probó que la estimulación de los nervios aferentes que inervan estos receptores induce bradicardia e hipotensión. Estos estudios fueron más tarde avanzados por Corneille Heymans quien ganó el premio Nobel por estos estudios en 1938. En la época de los setentas Cowley y Guyton produjeron denervación sino-aórtica en los perros y de esta manera demostraron la importancia fundamental del reflejo barorreceptor en la estabilización de la presión arterial.

The baroreceptor reflex is poorly known by most physicians even though is fundamental in stabilizing the blood pressure on a beat to beat basis and is crucial for survival. Its fascinating history is briefy reviewed in this article. In 1852 Claude Bernard discovered that the sympathetic nerves of the neck innervate the blood vessels of the skin of the rabbit. Edgar Douglas Adrian in 1932 demonstrated that the sympathetic nerves that innervate the blood vessels discharge spontaneously at a rate of 4-6 per second and thus discovered the physiological basis of the vasomotor tone. In the XIX century Ludwig Traube and Karl Constantine Ewald Hering discovered that blood pressure fluctuates synchronously with respiratory movements and Sigmund Mayer observed that there are also slow non respiratory fluctuations of blood pressure. In 1921 Heinrich Ewald Hering found that high pressure baroreceptors are located in the carotid sinuses and demonstrated that the stimulation of the afferent nerve that innervates it induces bradycardia and hypotension. These studies were further advanced by Corneille Heymans who won the Nobel Prize for these studies in 1938. Later Cowley and Guyton produced sino-aortic denervation in dogs and thereby could demonstrate the fundamental importance of the baroreceptor reflex in the stabilization of blood pressure.

Evidence that blood pressure remains under the control of arterial baroreceptors in renal hypertensive rats

The purpose of the present study was to determine the range of the influence of the baroreflex on blood pressure in chronic renal hypertensive rats. Supramaximal electrical stimulation of the aortic depressor nerve and section of the baroreceptor nerves (sinoaortic denervation) were used to obtain a global analysis of the baroreceptor-sympathetic reflex in normotensive control and in chronic (2 months) 1-kidney, 1-clip hypertensive rats. The fall in blood pressure produced by electrical baroreceptor stimulation was greater in renal hypertensive rats than in normotensive controls (right nerve: -47 ± 8 vs -23 ± 4 mmHg; left nerve: -51 ± 7 vs -30 ± 4 mmHg; and both right and left nerves: -50 ± 8 vs -30 ± 4 mmHg; P < 0.05). Furthermore, the increase in blood pressure level produced by baroreceptor denervation in chronic renal hypertensive rats was similar to that observed in control animals 2-5 h (control: 163 ± 5 vs 121 ± 1 mmHg; 1K-1C: 203 ± 7 vs 170 ± 5 mmHg; P < 0.05) and 24 h (control: 149 ± 3 vs 121 ± 1 mmHg; 1K-1C: 198 ± 8 vs 170 ± 5 mmHg; P < 0.05) after sinoaortic denervation. Taken together, these data indicate that the central and peripheral components of the baroreflex are acting efficiently at higher arterial pressure in renal hypertensive rats when the aortic nerve is maximally stimulated or the activity is abolished.

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

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.

Numerosas formas de evidência experimental obtidas nos últimos 37 anos demonstraram inequivocamente que a medula oblongata contém os principais circuitos responsáveis pela geração e manutenção do tono vasomotor e a regulação da pressão arterial. A visão atual que possuímos destes circuitos deriva em grande parte dos estudos de Pedro Guertzenstein, um estudante e mais tarde Professor de Fisiologia da UNIFESP e seus colaboradores. Nesta revisão nós sumarizamos os seus principais resultados assim como a nossa colaboração para uma melhor compreensão da regulação da pressão arterial em condições normais e patológicas.

Acute and chronic electrical activation of baroreceptor afferents in awake and anesthetized subjects

Electrical stimulation of baroreceptor afferents was used in the 1960's in several species, including human beings, for the treatment of refractory hypertension. This approach bypasses the site of baroreceptor mechanosensory transduction. Chronic electrical stimulation of arterial baroreceptors, particularly of the carotid sinus nerve (Hering's nerve), was proposed as an ultimate effort to treat refractory hypertension and angina pectoris due to the limited nature of pharmacological therapy available at that time. Nevertheless, this approach was abandoned in the early 1970's due to technical limitations of implantable devices and to the development of better-tolerated antihypertensive medications. More recently, our laboratory developed the technique of electrical stimulation of the aortic depressor nerve in conscious rats, enabling access to hemodynamic responses without the undesirable effect of anesthesia. In addition, electrical stimulation of the aortic depressor nerve allows assessment of the hemodynamic responses and the sympathovagal balance of the heart in hypertensive rats, which exhibit a well-known decrease in baroreflex sensitivity, usually attributed to baroreceptor ending dysfunction. Recently, there has been renewed interest in using electrical stimulation of the carotid sinus, but not the carotid sinus nerve, to lower blood pressure in conscious hypertensive dogs as well as in hypertensive patients. Notably, previous undesirable technical outcomes associated with electrical stimulation of the carotid sinus nerve observed in the 1960's and 1970's have been overcome. Furthermore, promising data have been recently reported from clinical trials that evaluated the efficacy of carotid sinus stimulation in hypertensive patients with drug resistant hypertension.

Inhibition of rhynchophylline on carotid sinus baroreceptor activity in anesthetized rats / 中国药理学与毒理学杂志

AIM To elucidate the effect of rhynchophylline(Rhy) on carotid sinus baroreceptor activity (CBA). METHODS By recording sinus nerve afferent discharge activity with isolated carotid sinus perfusion, parameters of CBA, such as peak slope (PS), peak integral value (PIV), threshold pressure (TP) and saturation pressure (SP) were examined. ①Rhy 10, 50, and 100 μmol·L-1, dissolved in K-H solution, was perfused into isolated carotid sinus, then the effects of Rhy on parameters of CBA were observed while intrasinus pressure was altered in a stepwise manner. ②NG-nitro-L-arginine methyl ester (L-NAME) 10 mmol·L-1, tetraethylammonium (TEA) 1 mmol·L-1 and Bay K8644 500 nmol·L-1 were perfused into isolated carotid sinus, and effects of them on the response of carotid baroreceptor to Rhy were observed. RESULTS ① By perfusing the isolated carotid sinus with Rhy 10 μmol·L-1, PS decreased from (19.2±0.3)% to (18.2±0.1)%·kPa-1and the PIV decreased from (219.3±3.3)% to (199.1±3.8)%, while TP and SP increased from (8.2±0.3) to (9.1±0.1)kPa and (21.5±0.1) to (22.1±0.1)kPa, respectively. By perfusing with Rhy 50 and 100 μmol·L-1, the changes in PS, TP and SP were in concentration-dependent manner, and this indicated inhibitory effect of Rhy on CBA. ②Pretreatment with L-NAME 100 μmol·L-1 did not affect inhibitory action of Rhy 50 μmol·L-1 on CBA. ③Pretreatment with TEA 1 mmol·L-1 had no effect on inhibitory effect of Rhy 50 μmol·L-1 on CBA. ④Pretreatment with Bay K8644 500 nmol·L-1 could mostly attenuate effect of Rhy 50 μmol·L-1 on CBA. CONCLUSION Rhy inhibits CBA via blocking calcium influx in baroreceptor nerve ending.

Effect of resveratrol on baroreceptor activity of carotid sinus in anesthetized male rats / 药学学报

This study is to evaluate the effect of resveratrol on carotid baroreceptor activity (CBA). The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized male rats with perfused isolated carotid sinus. Resveratrol (30, 60 and 120 μmol·L-1) inhibited CBA, which shifted FCCB to the right and downward. There was a marked decrease in peak slope (PS) and peak integral value (PIV) of carotid sinus nerve charge in a concentration-dependent manner. Pretreatment with Nω-nitro-L-arginine methyl ester (L-NAME, 100 μmol·L-1), an inhibitor of nitric oxide synthase (NOS), eliminated the inhibitory effect of resveratrol. Pretreatment with Bay K8644 (an agonist of L-type calcium channel, 500 nmol·L-1) abolished the effect of resveratrol on CBA. A potent inhibitor of tyrosine phosphatase (sodium orthovanadate, 1 mmol·L-1) did not influence the effect of resveratrol on CBA. Resveratrol inhibits carotid baroreceptor activity, which may be mediated by the locally released NO and decreased calcium influx. Several studies have showed a cardioprotective effect of resveratrol, with the penetrating study of resveratrol, it may show a potential value in the clinical treatment of cardiovascular disease as an alternative medicine.

Role of Central Vestibular Pathway on Control of Blood Pressure During Acute Hypotension in Rats

BACKGROUND AND OBJECTIVES: Central role of the vestibular system on control of blood pressure and interrelationships between the vestibular nucleus and solitary nucleus during acute hypotension were investigated in bilateral labyrinthectomized (BLX) or sinoaortic denervated (SAD) rats. Changes of electrical activity in the medial vestibular nucleus (MVN), solitary tract nucleus (STN), and rostral ventrolateral medullary nucleus (RVLM) were investigated in rats in while acute hypotension was induced by sodium nitroprusside (SNP). RESULTS: Evoked potential in MVN neuron caused by electrical stimulation of the peripheral vestibular system was composed of 3 waves with latencies of 0.48+/-.10 ms, 1.04+/-.09 ms and 1.98+/-.19 ms. Electrical stimulation to MVN or RVLM increased blood pressure. MVN at the induction of acute hypotension showed excitation in 61% of type I neurons and inhibition in 68% of type II neurons. In STN, acute hypotension produced excitation in 62.1% of neurons recorded in intact labyrinthine animals, inhibition in 72.3% of neurons recorded in BL animals, and excitation in 60% of recorded neurons in SAD animals. In RVLM, acute hypotension produced excitation in 66.7% of neurons recorded in intact labyrinthine animals and inhibition in 64.9% of neurons recorded in BL animals. In spatial distribution of STN neurons responded to acute hypotension, excitatory responses were mainly recorded in rostral and ventral portion, and inhibitory responses were mainly recorded in caudal and lateral portion. In RVLM, excitatory responses were mainly recorded in rostral and dorsomedial portion, and inhibitory responses were mainly recorded in caudal and ventrolateral portion. CONCLUSION: These results suggest that afferent signals from the peripheral vestibular receptors are transmitted to STN through the vestibular nuclei and assist to the baroreceptors for controlling blood pressure following acute hypotension.

Simulation of the Cardiovascular System Using PID Control Model / 대한의료정보학회지

OBJECTIVE: The electric analog circuit model can be used to analyse the various function of the cardio vascular system and the dynamic characteristics on each part of human body. According to the previous studies, viscous resistance, flow inertia, and vascular compliance in the cardiovascular system are analogous to resistance, inductance, and capacitance in electric circuit, so the cardiovascular system models have been represented by the electric circuit models. These approaches were to propose suitable models for the interested part of body and to simulate the various characteristics on the cardiovascular system. METHODS: This paper tried to put the characteristics of morphologic structure into the suggested electric circuit model. After setting parameter values of the model the dynamic characteristics of the cardio vascular system is simulated using VisSim, which is one of the simulation tools. RESULTS: The derived simulation results have represented major cardiovascular functions of normal adults. Also simulation results reflect the variation due to the pathophysiological state. CONCLUSION: The controller by baroreceptor, which is one of controllers to control the cardiovascular system, is appended in the model. The dynamic response characteristics and the procedure to restore blood pressure to normal state was observed by simulation lasted a certain period of bleeding.

Roles of NMDA receptors in arterial baroreceptor reflex in rostral ventrolateral medulla of rats / 第二军医大学学报

Objective: To study the roles of N methyl D aspartate acid (NMDA) receptors of glutamate in mediating the arterial baroreceptor reflex (ABR)in rostral ventrolateral medulla (RVLM) in rats. Methods: The blood pressure, heart rates and ABR were observed after the bilateral microinjection of 0.1 ?l 50 mmol/L ketamine into RVLM of ureth anesthetized rats. Results: Bilateral microinjection of ketamine into RVLM induced decrease of the blood pressure and heart rate ( P

Effects of Variable Infusion Rates of Propofol on Arterial Baroreflex Sensitivity / 대한마취과학회지

BACKGROUND: Induction of anesthesia with propofol caused a decrease in arterial blood pressure and systemic vascular resistance. This effects of propofol on the circulation can be more clarified by studying cardiovascular control mechanism such as baroreflex sensitivity during variable rate infusion of propofol. METHODS: The effects of three infusion rates of propofol (3, 6, 12 mg/kg/hr) to supplement 66% nitrous oxide in oxygen anesthesia on baroreflex sensitivity were studied and compared with awake value in 80 ASA I or II patients (20-55 years old, n=20 in each group). Baroreflex control of heat rate was studied by pertubing the patients' arterial pressure with 100 microgram of phenylephrine in each three infusion rates of propofol which was maintained at least 30 min without any surgical stimulation. RESULTS: Baroreflex slope representing baroreflex sensitivity among three infusion rates of propofol did not show any significant differences. The slope of each infusion rate was 8.4+/-0.7 at awake, 8.9+/- 1.7 at 3 mg/kg/hr, 8.0+/-1.3 at 6 mg/kg/hr, 7.2+/-1.0 at 12 mg/kg/hr, respectively. But, resetting of the reflex occured at low heart rates. CONCLUSIONS: Usual propofol-nitrous oxide-oxygen anesthesia was not associated with impairment of baroreflex sensitivity, but showed reflex resetting at low heart rates.

Age-related Difference of the Vagal Reflex and Baroreceptor Reflex under General Anesthesia with Enflurane / 대한마취과학회지

BACKGROUND: Baroreceptor reflex responds to the decrease in blood pressure caused by drug, dehydration, or severe bleeding. Vagal reflex caused by direct pressure on vagus nerve, the traction, or lung inflation develops bradycardia and severe arrhythmia. Lung inflation elicits a vasodepressor reflex, resulting in stimulation of the vagus nerve which causes a decrease in sympathetic outflow. METHODS: 75 patients who had elective surgery were divided into 3 groups according to the age, such as group I: or = 65 years of age. Lung inflation test has been performed at 20 cmH2O for 20 seconds. Baroreceptor was stimulated by lowering blood pressure with intravenous infusions of nitroglycerin. Baroreceptor sensitivity was assessed by measuring the decrease in blood pressure. Vagal reflex sensitivity was calculated by the subtraction of G2 (baroreceptor reflex sensitivity after introglycerin infusion) from G1 (heart rate response to lung inflation). RESULTS: Baroreceptor reflex induced by hypotension and vagal reflex originated from lung influe-nced the heart rate inversely when lung inflated. Baroreceptor reflex sensitivity was highest in younger patients and lowest in older patients when nitroglycerin infused. Vagal reflex sensitivity was highest in older patients and lowest in younger patients. CONCLUSIONS: Baroreceptor reflex was most sensitive in younger patients, but vagal reflex was moresensitive in older patients.

Cardiovascular Effects of Endogenous GABA in the Nucleus Tractus Solitarius

BACKGROUND: The nucleus tractus solitarius (NTS), the region of the brain stem in which primary baroreceptor afferents teminate, is critically important in the normal regulation of arterial pressure (AP). In the NTS, excitatory amino acids such as L-glutamate serve as the main neurotransmitter in the regulation of AP. However, the function of GABA in the NTS has not been established. To test the function of GABA, we applied GABAergic agents to the NTS. METHODS: The experiments were conducted on adult male Sprague-Dawley rats weighing 300-500g. A cannula (PE-50 tubing filled with heparinized saline) was inserted into the femoral artery for recording of AP and heart rate(HR). Another cannula was inserted into the femoral vein for administration of nitroprusside or phenylephrine. After rats were placed on a sterotaxic instrument, the dorsal surface of the medulla was exposed, and with the aid of a surgical microscope, the NTS was visualized. Drug injections were made into the NTS using single- or three-barreled grass micropipettes pulled to an outer diameter of 80-100(micro)m and connected to a 1(micro)l Hamilton syringe. RESULTS: The follwing results were obtained in this experiment. Injection into the NTS of 10 or 20 nmol nipecitic acid, a selective inhibitor of GABA untake, produced an increase in AP. The pressor responses evoked by two doses of nipecotic acid were not significantly different. Injection of GABA(A) agonist, musciml(5 pmol in 80 nl artificial CSF) and GABA(B) agonist, baclofen (20 pmol in 80 nl) into the NTS of urethane-anesthetized rats prodused an increase in AP of 16.6+/-1.3 and 27.6+/-1.5 mmHg, respectively. Thus the pressor response to GABA(B) agonist was greater than to GABA(A) agonist. On the other hand, microinjection of GABA(A) antagonist, bicuculline and GABA(B) antagonist, phaclofen into the NTS decreased AP by approximately 13.4+/-1.0 and 20.9+/- mmHg, respectively. Thus injection of nipecotic acid into the NTS was greater in control group compared with the muscimiol or baclofen groups. The AP changes caused by i.v. injection of nitroprusside or phenylephrine were smallest in control group and greatest in the baclofen group. When calculated as baroreflex sensitivity, the change was greatest in control group and smallest in the baclofen group. CONCLUSION: From these results it was concluded that GABA in the NTS plays an important role in the regulation of AP, especially through GABA(B) receptors, and have an inhibitory effect on baroreceptor reflex.