Mechanosensitive ion channels (MSCs) are key molecules in the mechano-electrical transduction of arterial baroreceptors. Among them, acid-sensing ion channel 2 (ASIC2) and transient receptor potential vanilloid subfamily member 1 (TRPV1) have been studied extensively and documented to play important roles. In this study, experiments using aortic arch-aortic nerve preparations isolated from rats revealed that both ASIC2 and TRPV1 are functionally necessary, as blocking either abrogated nearly all pressure-dependent neural discharge. However, whether ASIC2 and TRPV1 work in coordination remained unclear. So we carried out cell-attached patch-clamp recordings in HEK293T cells co-expressing ASIC2 and TRPV1 and found that inhibition of ASIC2 completely blocked stretch-activated currents while inhibition of TRPV1 only partially blocked these currents. Immunofluorescence staining of aortic arch-aortic adventitia from rats showed that ASIC2 and TRPV1 are co-localized in the aortic nerve endings, and co-immunoprecipitation assays confirmed that the two proteins form a compact complex in HEK293T cells and in baroreceptors. Moreover, protein modeling analysis, exogenous co-immunoprecipitation assays, and biotin pull-down assays indicated that ASIC2 and TRPV1 interact directly. In summary, our research suggests that ASIC2 and TRPV1 form a compact complex and function synergistically in the mechano-electrical transduction of arterial baroreceptors. The model of synergism between MSCs may have important biological significance beyond ASIC2 and TRPV1.
Acid Sensing Ion Channels/physiology* ; Animals ; HEK293 Cells ; Humans ; Pressoreceptors/physiology* ; Rats ; TRPV Cation Channels/physiology*

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.
Animals ; Baroreflex ; physiology ; Blood Pressure ; physiology ; Cardiovascular Diseases ; metabolism ; physiopathology ; Diabetes Mellitus ; metabolism ; physiopathology ; Humans ; Ion Channels ; metabolism ; Pressoreceptors ; metabolism

Orthostatic hypotension is most common in elderly people, and its prevalence increases with age. Attenuation of the vestibulo-sympathetic reflex (VSR) is commonly associated with orthostatic hypotension. In this study, we investigated the role of glutamate on the vestibulo-solitary projection of the VSR pathway to clarify the pathophysiology of orthostatic hypotension. Blood pressure and expression of both pERK and c-Fos protein were evaluated in the nucleus tractus solitarius (NTS) after microinjection of glutamate into the medial vestibular nucleus (MVN) in conscious rats with sodium nitroprusside (SNP)-induced hypotension that received baroreceptor unloading via sinoaortic denervation (SAD). SNP-induced hypotension increased the expression of both pERK and c-Fos protein in the NTS, which was abolished by pretreatment with glutamate receptor antagonists (MK801 or CNQX) in the MVN. Microinjection of glutamate receptor agonists (NMDA or AMPA) into the MVN increased the expression of both pERK and c-Fos protein in the NTS without causing changes in blood pressure. These results indicate that both NMDA and AMPA receptors play a significant role in the vestibulo-solitary projection of the VSR pathway for maintaining blood pressure, and that glutamatergic transmission in this projection might play a key role in the pathophysiology of orthostatic hypotension.
Aged ; Animals ; Blood Pressure ; Denervation ; Excitatory Amino Acid Antagonists ; Glutamic Acid* ; Humans ; Hypotension* ; Hypotension, Orthostatic ; Microinjections ; N-Methylaspartate ; Nitroprusside ; Pressoreceptors ; Prevalence ; Rats* ; Receptors, AMPA ; Receptors, Glutamate ; Reflex ; Sodium* ; Solitary Nucleus ; Vestibular Nuclei

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.
Animals ; Blood Pressure ; Denervation ; Glutamic Acid ; Hypotension* ; Neurons ; Nitroprusside ; Pressoreceptors* ; Protein Kinases ; Rats*

OBJECTIVE: The vestibular system contributes control of blood pressure during postural changes through the vestibulosympathetic reflex. In the vestibulosympathetic reflex, afferent signals from the peripheral vestibular receptors are transmitted to the vestibular nuclei, rostral ventrolateral medullary nuclei, and then to the intermediolateral cell column of the thoracolumbar spinal cord. Physiological characteristics of the vestibulosympathetic reflex in terms of neurogenic and humoral control of blood pressure were investigated in this study. METHODS: Conscious rats with sinoaortic denervation were used for removal of baroreceptors in reflex control of blood pressure, and hypotension was induced by intravenous infusion of sodium nitroprusside (SNP). Expression of c-Fos protein was measured in the medial vestibular nuclei (MVN), rostral vestrolateral medullary nuclei(RVLM), and intermediolateral cell column (IMC) in T4-7, and levels of blood epinephrine were measured following SNP-induced hypotension. RESULTS: SNP-induced hypotension significantly increased expression of c-Fos protein in the MVN, RVLM, and IMC, also significantly increased level of blood epinephrine compared to normotensive control animals. CONCLUSION: These results suggest that the vestibulosympathetic reflex regulates blood pressure through neurogenic control including MVN, RVLM, and IMC, also through humoral control including epinephrine secretion by the adrenal medulla following SNP-induced hypotension. The physiological characteristics of the reflex may contribute to basic treatment of impairment of blood pressure control during postural changes.
Adrenal Medulla ; Animals ; Blood Pressure ; Denervation ; Epinephrine ; Hypotension ; Infusions, Intravenous ; Nitroprusside ; Pressoreceptors ; Rats ; Reflex ; Spinal Cord ; Vestibular Nuclei

Carotid Body Tumor ; surgery ; Humans ; Hypertension ; Pressoreceptors

BACKGROUND: It has been known that positive end-expiratory pressure (PEEP) increases the vasoconstriction threshold by baroreceptor unloading. We compared the effect on the thermoregulatory responses according to anesthetic techniques between an inhalation anesthesia with desflurane and a total intravenous anesthesia (TIVA) with propofol and reminfentanil when PEEP was applied in patients undergoing tympanoplasty. METHODS: Forty-six patients with a scheduled tympanoplasty were enrolled and the patients were divided in two study groups. Desflurane was used as an inhalation anesthetic in group 1 (n = 22), while TIVA with propofol and remifentanil was used in group 2 (n = 24). PEEP was applied by 5 cmH2O in both groups and an ambient temperature was maintained at 22-24degrees C during surgery. The core temperature and the difference of skin temperature between forearm and fingertip were monitored for about 180 minutes before and after the induction of general anesthesia. RESULTS: The final core temperature was significantly higher in group 2 (35.4 +/- 0.7degrees C) than in group 1 (34.9 +/- 0.5degrees C). Peripheral thermoregulatory vasoconstriction was found in 5 subjects (23%) in group 1 and in 21 subjects (88%) in group 2. The time taken for reaching the thermoregulatory vasoconstriction threshold was 151.4 +/- 19.7 minutes in group 1 and 88.9 +/- 14.4 minutes in group 2. CONCLUSIONS: When PEEP will be applied, anesthesia with TIVA may have more advantages in core temperature preservation than an inhalation anesthesia with desflurane.
Anesthesia ; Anesthesia, General ; Anesthesia, Inhalation* ; Anesthesia, Intravenous ; Body Temperature Regulation ; Forearm ; Humans ; Inhalation ; Positive-Pressure Respiration ; Pressoreceptors ; Propofol ; Skin Temperature ; Tympanoplasty* ; Vasoconstriction

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.
Animals ; Baroreflex* ; Blood Pressure ; Denervation ; Hypotension* ; Hypotension, Orthostatic ; Neurons ; Nitroprusside ; Pressoreceptors ; Protein Kinases ; Rats* ; Reflex* ; Solitary Nucleus*

OBJECTIVETo observe the regulation of heart rate to cardiac pump function in the phase of negative force-frequency relationship and their possible mechanisms.

METHODSThe left ventricular pressure, aortic pressure, and cardiac output were measured in isolated working heart of rat from 240 to 300 beats/min of pacing rate.

RESULTSCardiac output of isolated working heart was decreased by a proximally 20% (P < 0.01) with the increase in the pacing rate from 240 to 300 beats/min. Left ventricular end-systolic pressure (LVESP) was declined by 4.8% (P < 0.05), but left ventricular end-diastolic pressure (LVEDP) was elevated by 139% (P < 0.01) with an increase in the pacing rate. Left atrium was enlarged at 300 beats/min of pacing rate. The time from peak to 75% relaxation in left ventricular pressure was shortened with the increased pacing rate. Pressure at aortic valve close was raised (P < 0.01) and ejection duration was shortened with the increased pacing rate (P < 0.01).

CONCLUSIONThose above results suggest that there are different mechanisms between the depressed cardiac output at higher heart rate and negative force-frequency relationship. The frequency-dependent acceleration of relaxation facilitates the decline of left ventricular pressure, and then may elevate the pressure of aortic valve close in the condition that the shape of aortic pressure curve stays the same. Therefore, the ejection duration is shortened at higher pacing rate. The shortened ejection duration may induce a decrease in stroke volume of the left ventricle. The increment of heart rate is not enough to compensate the decreased stroke volume. Finally, cardiac output shows a decrease at higher heart rate.

Animals ; Blood Pressure ; Cardiac Output ; Heart Rate ; physiology ; Male ; Pressoreceptors ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo develop a system for automatically controlling carotid sinus pressure in the study on baroreceptors.

METHODSThe preparation containing carotid sinus with parts of the connected vessels and carotid sinus nerve (CS-CSN) were isolated and perfused. A critical pressure controlling component (PRE-U, Hoerbiger, Deutschland) dictated by a computer was integrated into the system to clamp the intrasinus pressure. The pressure command and the relevant intrasinus pressure were compared to evaluate the validity of the pressure controlling system.

RESULTSA variety of sinus pressure-controlling patterns, including pulsation, ramp and step pressures, could be achieved accurately by using the system, and the pressure-dependent discharge activities of sinus nerve were confirmed.

CONCLUSIONThis system for clamping carotid sinus pressure could realize multiple pressure-controlling patterns and is a useful and flexible pressure controlling method that could applied in the study on mechano-electric transduction of baroreceptors.

Animals ; Blood Pressure ; Carotid Sinus ; innervation ; physiology ; Nerve Fibers ; physiology ; Pressoreceptors ; physiology ; Rabbits