scholarly journals Cardiac Hypertrophy Caused by Hyperthyroidism in Rats: Role of ATF-6 and TRPC1 Channels

2021 ◽  
Author(s):  
Nuriye Ezgi Bektur Aykanat ◽  
Erhan Şahin ◽  
Sedat Kaçar ◽  
Rıdvan Bağcı ◽  
Şerife Karakaya ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Er Stress ◽  
Transient Receptor Potential ◽  
Tap Water ◽  
Receptor Potential ◽  
Male Rats ◽  
Control Group ◽  
Critical Pathways ◽  
Trpc1 Channels ◽  
Tsh Levels

Hyperthyroidism influences the development of cardiac hypertrophy. Transient receptor potential canonical channels (TRPCs) and ER stress are regarded as critical pathways in cardiac hypertrophy.Hence, we aimed to identify the TRPCs associated with ER stress in hyperthyroidism-induced cardiac hypertrophy.20 adult Wistar albino male rats were used in the study.The control group was fed with standard food and tap water. The group with hyperthyroidism was also fed with standard rat food, along with tap water that contained 12 mg/L of thyroxine for four weeks.At the end of the fourth week, the serum-free T3, T4, and TSH levels of the groups were measured. The left ventricle of each rat was used for histochemistry, immunohistochemistry, western blot, total antioxidant capacity (TAC), and total oxidant status (TOS) analysis. As per our results, ATF-6, IRE-1, and TRPC1, which play a significant role in cardiac hypertrophy caused by hyperthyroidism, showed increased activation. Moreover, TOS and fT3 levels increased, while TAC and TSH levels decreased. With the help of the literature review in our study, we could, for the first time, indicate that the increased activation, in particular of ATF-6, IRE-1, and TRPC1-induced deterioration of the Ca2+ ion balance, leads to hypertrophy in hyperthyroidism due to heart failure.

Abstract 138: Transient Receptor Potential Channel C1 Deficiency Protects the Murine Heart from Pressure Overload

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Malini Seth ◽  
Zhu-Shan Zhang ◽  
Lan Mao ◽  
Jarrett Burch ◽  
Victoria Graham ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Transient Receptor Potential ◽  
Pressure Overload ◽  
Receptor Potential ◽  
Receptor Activation ◽  
Trpc Channels ◽  
Loss Of Function ◽  
Aortic Banding ◽  
Trpc1 Channels ◽  
Transient Receptor

Transient receptor potential canonical (TRPC) channels are non-selective cation channels that are activated in response to G-protein coupled receptor activation, depletion of internal stores and mechanical stretch. Recent reports suggest that cardiac TRPC channels mediate calcineurin dependent cardiac hypertrophy, yet few details exist as to the mechanism for activation of these channels. Here, we provide evidence that TRPC1 channels are the dominant TRPC channel in mouse cardiomyocytes and cardiac TRPC1 protein expression is augmented by seven fold following thoracic aortic banding (TAC). In addition, we provide the first loss of function studies to show that mice lacking TRPC1 channels developed significantly less cardiac hypertrophy following pressure overload induced by thoracic aortic banding suggesting that TRPC1 may confer deleterious calcium entry. Whole cell voltage clamp studies of isolated adult cardiomyocytes reveal a non-selective cation current that is induced by pressure overload that is absent in TRPC1−/− cardiomyocytes and in which TRP blockers such as gadolinium, 2-amino biphenyl boric acid and SKF96365 inhibit the TAC induced current. Finally, neonatal cardiomyocytes lacking functional TRPC1 display reduced TRPC current in response to cell stretch or angiotensin-II; the functional consequence of which includes reduced calcium oscillation frequency and reduced BNP expression. These results provide the first loss of function evidence for TRPC1 channels in cardiac hypertrophy and implicate TRPC1 as a stretch activated channel.

The Action of Shenmai Injection on the Inflammation and Proliferation of Smooth Muscle Cells of the Airway in Asthmatic Rats

2021 ◽  
Vol 11 (3) ◽  
pp. 386-391
Author(s):  
He Zhu ◽  
Yali Guo ◽  
Xiaoli Wang ◽  
Min Zhu ◽  
Jiahui Lei ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Muscle Cells ◽  
Interleukin 4 ◽  
Nuclear Antigen ◽  
Control Group ◽  
Airway Smooth Muscle Cells ◽  
Shenmai Injection

To observe the effect of transient receptor potential ankyrin 1 (TRPA1) channel on the proliferation and inflammation of airway smooth muscle cells (SMC) in asthmatic rats, the rats were randomly allocated into three treatment groups: control, asthma, and Shenmai injection (SMI), with 15 rats in each group. Asthmatic rat models were induced by ovalbumin (OVA) inhalation. Rats in the control and asthma groups were intraperitoneally injected 2 mL NS daily, whereas rats in the SMI treatment group were intraperitoneally injected with 2 mL SMI daily. RT-qPCR and western blotting were used to test for TRPA1 and proliferating cell nuclear antigen (PCNA) mRNA and protein expression. ELISA was used to test the expression of interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13) in the serum. Compared with the control group, there were significantly higher levels of TRPA1 and PCNA mRNA and protein, as well as of IL-4, IL-5, and IL-13 in asthmatic rats (P< 0.05). After SMI treatment, there was significantly lower expression of TRPA1, PCNA, IL-4, IL-5, and IL-13 compared to the levels in asthmatic rats (P < 0.05). TRPA1, IL-4, IL-5, and IL-13 were highly expressed in the tracheal SMC of asthmatic rats. Inhibiting TRPA1, IL-4, IL-5, and IL-13 using SMI may be one of the mechanisms that can intervene chronic airway inflammation and asthma proliferation.

Responses of thoracic spinal neurons to activation and desensitization of cardiac TRPV1-containing afferents in rats

2006 ◽  
Vol 291 (6) ◽  
pp. R1700-R1707 ◽  
Author(s):  
Chao Qin ◽  
Jay P. Farber ◽  
Kenneth E. Miller ◽  
Robert D. Foreman
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Male Rats ◽  
Transient Receptor Potential Vanilloid ◽  
Spinal Neurons ◽  
Thoracic Spinal ◽  
Afferent Fibers ◽  
Study Results ◽  
Transient Receptor ◽  
Excitatory Responses

The purpose of this study was to examine how upper thoracic spinal neurons responded to activation and desensitization of cardiac transient receptor potential vanilloid-1 (TRPV1)-containing afferent fibers. Extracellular potentials of single T3 spinal neurons were recorded in pentobarbital-anesthetized, paralyzed, and ventilated male rats. To activate cardiac nociceptive receptors, a catheter was placed in the pericardial sac to administer various chemicals: bradykinin (BK; 10 μg/ml, 0.2 ml), capsaicin (CAP, 10 μg/ml, 0.2 ml), or a mixture of algesic chemicals (AC; 0.2 ml) containing adenosine 10−3 M, BK, serotonin, histamine, and PGE2, 10−5 M for each. Spinal neurons that responded to intrapericardial BK and/or CAP were used in this study. Results showed that 81% (35/43) of the neurons had excitatory responses to both intrapericardial BK and CAP, and the remainder responded to either BK or CAP. Intrapericardial resiniferatoxin (RTX) (0.2 μg/ml, 0.2 ml, 1 min), which desensitizes TRPV1-containing nerve endings, abolished excitatory responses to both BK ( n = 8) and CAP ( n = 7), and to AC ( n = 5) but not to somatic stimuli. Intrapericardial capsazepine (1 mg/ml, 0.2 ml, 3 min), a specific antagonist of TRPV1, sharply attenuated excitatory responses to CAP in 5/5 neurons, but responses to BK in 5/5 neurons was maintained. Additionally, intrapericardial capsazepine had no significant effect on excitatory responses to AC in 3/3 neurons. These data indicated that intrapericardial BK-initiated spinal neuronal responses were linked to cardiac TRPV1-containing afferent fibers, but were not dependent on TRPV1. Intraspinal signaling for cardiac nociception was mediated through CAP-sensitive afferent fibers innervating the heart.

Abstract 115: Reduction of Trpv1 Activity in Aortic Baroreceptor Neurons in Diabetic Neuropathy: Role of Brain-derived Neurotrophic Factor

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Yingying Tan ◽  
Qi Zhang
Keyword(s):  
Diabetic Neuropathy ◽  
Transient Receptor Potential ◽  
Kinase Inhibitor ◽  
Receptor Potential ◽  
Diabetic Rats ◽  
Control Group ◽  
Transient Receptor Potential Vanilloid ◽  
Peak Current Density ◽  
Inward Current ◽  
Pre Treatment

It has been well documented that diabetes mellitus is associated with cardiovascular autonomic neuropathy including dysfunction of arterial baroreflex. The mechanisms underlying diabetes-induced baroreflex dysfunction remain poorly understood. Here we investigated the function and expression of transient receptor potential vanilloid 1 (TRPV1) in aortic baroreceptor (AB) neurons isolated from streptozotocin-induced diabetic rats between 4 and 8 weeks after onset of diabetes. AB neurons in nodose ganglion were retrograde-labeled by a transported fluorescent dye, Dil. Using the whole-cell patch clamp, we found that the inward current activated by the application of capsaicin (1 μM) was significantly smaller in AB neurons from diabetic rats compared with controls. The mean peak current density of capsaicin-induced currents was 145.7 ± 24.7 pA/pF (n = 16) in diabetic neurons and 269.3 ± 31.8 pA/pF (n =15) in controls, respectively. The duration of inward current was decreased 51% in diabetic rats compared with the control group. These evoked currents were completely blocked by the capsaicin antagonist capsazepine. In addition, capsaicin-induced desensitization of TRPV1 was up-regulated, whereas TRPV1 re-sensitization was down-regulated in AB neurons from diabetic rats. Immunofluorescence staining studies demonstrated that the percentage of TRPV1-positive neurons was 50.2 ± 5.0% in control rats and 38.2 ± 1.9% in diabetic rats, respectively. This reduction in TRPV1-positive neurons in AB neurons in diabetic rats was significant (n = 11, P < 0.01). In addition, the reductions in TRPV1 currents and positive neurons s in diabetic rats were normalized by pre-treatment with anti-BDNF antibody or K252a, a TrkB tyrosine kinase inhibitor. Furthermore, incubation with BDNF caused a large reduction in TRPV1 currents in AB neurons from control rats, and the number of AB neurons with BDNF immunoreactivity was greater in diabetic than control rats. These results suggest that reduced expression and function of TRPV1 are involved in the attenuation of baroreceptor neuron excitability, and increased BDNF activity in these neurons likely contributes to the reduction in TRPV1 function through TrkB receptor stimulation in diabetic neuropathy.

scholarly journals Fructose feeding and intermittent hypoxia affect ventilatory responsiveness to hypoxia and hypercapnia in rats

2004 ◽  
Vol 97 (4) ◽  
pp. 1387-1394 ◽  
Author(s):  
Evelyn H. Schlenker ◽  
Yijiang Shi ◽  
Joni Wipf ◽  
Douglas S. Martin ◽  
Curtis K. Kost
Keyword(s):  
Intermittent Hypoxia ◽  
Plasma Insulin ◽  
Tap Water ◽  
Minute Ventilation ◽  
Acute Hypoxia ◽  
Male Rats ◽  
Control Group ◽  
Insulin Levels ◽  
Ventilatory Responses ◽  
Plasma Insulin Levels

We hypothesized that, in male rats, 10% fructose in drinking water would depress ventilatory responsiveness to acute hypoxia (10% O2 in N2) and hypercapnia (5% CO2 in O2) that would be depressed further by exposure to intermittent hypoxia. Minute ventilation (V̇e) in air and in response to acute hypoxia and hypercapnia was evaluated in 10 rats before fructose feeding (FF), during 6 wk of FF, and after FF was removed for 2 wk. During FF, five rats were exposed to intermittent air and five to intermittent hypoxia for 13 days. Six rats given tap water acted as control and were exposed to intermittent air and subsequently intermittent hypoxia. In FF rats, plasma insulin levels increased threefold in the rats exposed to intermittent hypoxia and during washout returned to levels observed in rats exposed to intermittent air. During FF, ventilatory responsiveness to acute hypoxia was depressed because of decreased tidal volume (Vt) responsiveness. During washout, V̇e decreased as a result of decreased Vt and frequency of breathing, and the ventilatory responsiveness to hypoxia in intermittent hypoxia rats did not recover. In all rats, the ventilatory responses to hypercapnia were decreased during FF and recovered after washout because of an increased Vt responsiveness. In the control group, hypoxic responsiveness was not depressed after intermittent hypoxia and was augmented after washout. Thus FF attenuated the ventilatory responsiveness of conscious rats to hypoxia and hypercapnia. Intermittent hypoxia interacted with FF to increase insulin levels and depress ventilatory responses to acute hypoxia that remained depressed during washout.

scholarly journals Antinociceptive Effects of Emodin on CFA-Induced Inflammatory Pain in Rats

2020 ◽  
Vol 15 (7) ◽  
pp. 1934578X2094200
Author(s):  
Wan Ni ◽  
Nianyun Wang ◽  
Shenglan Tian ◽  
Qingbang Xu
Keyword(s):  
Mrna Expression ◽  
Inflammatory Pain ◽  
Transient Receptor Potential ◽  
Interleukin 1 ◽  
Receptor Potential ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Transient Receptor Potential Vanilloid ◽  
Tnf Α ◽  
Transient Receptor

The effect of emodin on complete Freund’s adjuvant (CFA)-induced inflammatory pain in rats and its potential molecular mechanism was investigated. For this, a rat model of inflammatory pain induced by CFA was established and rats were treated with emodin by intraperitoneal injection. The pain threshold was evaluated by the von Frey, thermo hyperalgesia, and cold plate tests. The mRNA expression of transient receptor potential channel ankyrin type-1 ( Trpa1) and transient receptor potential vanilloid 1 ( Trpv1) was detected by quantitative reverse transcription polymerase chain reaction, and the level of inflammatory cytokines was determined by enzyme-linked immunosorbent assay. The mechanical and thermal pain thresholds of CFA-treated rats were significantly lower than those of the control rats, while the paw withdrawal responses in response to cold stimulation were higher than that of the control group. Emodin treatment significantly improved CFA-induced hyperalgesia. Further results showed that emodin inhibits the upregulation of Trpa1 and Trpv1 mRNA expression in the dorsal root ganglion (DRG) of rats with inflammatory pain compared with the control group. Emodin also significantly reduced the levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) in the serum of rats with inflammatory pain. Thus, emodin may inhibit hyperalgesia induced by inflammatory stimulation by downregulating the mRNA expression of Trpa1 and Trpv1 in DRG neurons and reducing the levels of TNF-α, IL-1β, and IL-6.

Ca2+ pathway involved in the refilling of store sites in rat adrenal medullary cells

2009 ◽  
Vol 296 (4) ◽  
pp. C889-C899 ◽  
Author(s):  
Hidetada Matsuoka ◽  
Keita Harada ◽  
Tomoya Ikeda ◽  
Kouta Uetsuki ◽  
Takeyoshi Sata ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Outward Current ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Experimental Result ◽  
Intracellular Ca ◽  
Serca Pump ◽  
Potential Channels ◽  
Trpc1 Channels ◽  
Transient Receptor

It has been suggested that store-operated Ca2+ entry (SOC) facilitates catecholamine secretion and synthesis in bovine adrenal medullary (AM) cells. However, there has been no experimental result clearly showing that cation channel activity is enhanced by store Ca2+ depletion. Thus the present experiments were undertaken to address the issue of whether rat AM cells have SOC channels. Inhibition of the sarco(endo)plasmic reticulum Ca2+ (SERCA) pump resulted in a sustained increase in intracellular Ca2+ concentration ([Ca2+]i) in rat AM cells. This increase was completely suppressed by 2 mM Ni2+ but not by 100 μM D600. A bath application of Ni2+, but not D600, produced an outward current at −60 mV in rat AM cells, whereas exposure to a SERCA pump inhibitor did not affect either the whole cell current level or the Ni2+-induced outward current. The refilling of intracellular store sites was suppressed by the addition of Ni2+ to the perfusate. RT-PCR revealed that transcripts for transient receptor potential channels 1 (TRPC1) and 5 (TRPC5) were present in rat adrenal medullas. Immunocytochemistry showed that TRPC1 channels, which have been implicated in SOC in certain types of cells, were mainly localized in the endoplasmic reticulum (ER) and not in the plasma membrane, and that STIM1, a Ca2+ sensor in the ER, was not expressed in rat AM cells. On the basis of these results, we conclude that rat AM cells lack the SOC mechanism.

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