scholarly journals Role of Transient Receptor Potential Vanilloid 4 in Vascular Function

2021 ◽  
Vol 8 ◽  
Author(s):  
Liangliang Liu ◽  
Mengting Guo ◽  
Xiaowang Lv ◽  
Zhiwei Wang ◽  
Jigang Yang ◽  
...  

Transient receptor potential vanilloid 4 (TRPV4) channels are widely expressed in systemic tissues and can be activated by many stimuli. TRPV4, a Ca2+-permeable cation channel, plays an important role in the vasculature and is implicated in the regulation of cardiovascular homeostasis processes such as blood pressure, vascular remodeling, and pulmonary hypertension and edema. Within the vasculature, TRPV4 channels are expressed in smooth muscle cells, endothelial cells, and perivascular nerves. The activation of endothelial TRPV4 contributes to vasodilation involving nitric oxide, prostacyclin, and endothelial-derived hyperpolarizing factor pathways. TRPV4 activation also can directly cause vascular smooth muscle cell hyperpolarization and vasodilation. In addition, TRPV4 activation can evoke constriction in some specific vascular beds or under some pathological conditions. TRPV4 participates in the control of vascular permeability and vascular damage, particularly in the lung capillary endothelial barrier and lung injury. It also participates in vascular remodeling regulation mainly by controlling vasculogenesis and arteriogenesis. This review examines the role of TRPV4 in vascular function, particularly in vascular dilation and constriction, vascular permeability, vascular remodeling, and vascular damage, along with possible mechanisms, and discusses the possibility of targeting TRPV4 for therapy.

2020 ◽  
Vol 5 (6) ◽  
pp. 370-377
Author(s):  
V. O. Stetska ◽  
◽  
O. F. Moroz ◽  
T. V. Dovbynchuk ◽  
G. M. Tolstanova ◽  
...  

Although it was shown that transient receptor potential channels are expressed in the intestinal and myometrial smooth muscle cells and can control gastrointestinal motility and regulate uterine contractility the specific role of transient receptor potential vanilloid-type 4 channel in smooth muscle cells contraction remain largely unknown. The purpose of the study was to test the action of transient receptor potential vanilloid-type 4 selective agonist GSK1016790A on smooth muscle cells contraction in rat’s colon with experimental Parkinson`s disease and in the pregnant rat uterus (18-22 days of gestation). Material and methods. The Parkinson’s disease was induced by single unilateral stereotaxic injection of 12 μg 6-OHDA. The percentage of destroyed dopaminergic neurons was evaluated in apomorphine test (0.5 mg/kg, i.p.) at 1 and 2 weeks after surgery. The water content in faeces was evaluated on the 1st day, then at the 3rd week and 7th month of the experiment. The daily volume of water consumption and gastrointestinal transit time were evaluated at the 3rd week and 7th month after surgery. The action of transient receptor potential vanilloid-type 4 agonist GSK1016790A (0.3 mmol) on smooth muscle cells of colon and myometrium strips contraction was estimated by isometric tension recording. Results and discussion. The apomorphine test showed a progressive increase in the number of turns between the 1st and 2nd week after inducing 6-OHDA-PD. The water content in faeces was increased at the 3rd week (P<0.05) vs. 1st day of the experiment. The rats with 6-OHDA-PD drank less water vs. placebo and intact groups. We observed a 17% delayed GI transit time in 6-OHDA-PD rats (P<0.01) vs. intact and 21% vs. sham-lesioned group of rats 3 weeks after the 6-OHDA treatment. 7 months after the surgery GI transit time was increased more than twice in all studied groups. Transient receptor potential vanilloid-type 4 agonist action on smooth muscle cells of 6-OHDA-PD rats was reduced by 21% compared to intact group and by 46% in sham-lesioned group (P<0.05). After the application of GSK1016790A the rat myometrium strips a 28.4% (P<0.05) decrease of the contractile force was recorded. It was accompanied by a 30.7% (P<0.05) decline of the muscle work estimated as the area under the contractile curve. Suppression of the amplitude of uterine contraction was also followed by a 39.7% (P<0.05) decline of the rise time constant of peaks but unchanged peak duration at the half maximal amplitude. Conclusion. We conclude that pharmacological activation of transient receptor potential vanilloid-type 4 ion channels by their selective agonist GSK1016790A decreased the contractile activity of both colon smooth muscle cells in Parkinson’s disease rats’ model and the myometrium in pregnant rats


2021 ◽  
Vol 22 (7) ◽  
pp. 3360
Author(s):  
Mee-Ra Rhyu ◽  
Yiseul Kim ◽  
Vijay Lyall

In addition to the sense of taste and olfaction, chemesthesis, the sensation of irritation, pungency, cooling, warmth, or burning elicited by spices and herbs, plays a central role in food consumption. Many plant-derived molecules demonstrate their chemesthetic properties via the opening of transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) channels. TRPA1 and TRPV1 are structurally related thermosensitive cation channels and are often co-expressed in sensory nerve endings. TRPA1 and TRPV1 can also indirectly influence some, but not all, primary taste qualities via the release of substance P and calcitonin gene-related peptide (CGRP) from trigeminal neurons and their subsequent effects on CGRP receptor expressed in Type III taste receptor cells. Here, we will review the effect of some chemesthetic agonists of TRPA1 and TRPV1 and their influence on bitter, sour, and salt taste qualities.


2002 ◽  
Vol 92 (4) ◽  
pp. 1594-1602 ◽  
Author(s):  
Michele Sweeney ◽  
Sharon S. McDaniel ◽  
Oleksandr Platoshyn ◽  
Shen Zhang ◽  
Ying Yu ◽  
...  

Asthma is characterized by airway inflammation, bronchial hyperresponsiveness, and airway obstruction by bronchospasm and bronchial wall thickening due to smooth muscle hypertrophy. A rise in cytosolic free Ca2+ concentration ([Ca2+]cyt) may serve as a shared signal transduction element that causes bronchial constriction and bronchial wall thickening in asthma. In this study, we examined whether capacitative Ca2+ entry (CCE) induced by depletion of intracellular Ca2+ stores was involved in agonist-mediated bronchial constriction and bronchial smooth muscle cell (BSMC) proliferation. In isolated bronchial rings, acetylcholine (ACh) induced a transient contraction in the absence of extracellular Ca2+ because of Ca2+ release from intracellular Ca2+ stores. Restoration of extracellular Ca2+in the presence of atropine, an M-receptor blocker, induced a further contraction that was apparently caused by a rise in [Ca2+]cyt due to CCE. In single BSMC, amplitudes of the store depletion-activated currents ( I SOC) and CCE were both enhanced when the cells proliferate, whereas chelation of extracellular Ca2+ with EGTA significantly inhibited the cell growth in the presence of serum. Furthermore, the mRNA expression of TRPC1, a transient receptor potential channel gene, was much greater in proliferating BSMC than in growth-arrested cells. Blockade of the store-operated Ca2+channels by Ni2+ decreased I SOC and CCE and markedly attenuated BSMC proliferation. These results suggest that upregulated TRPC1 expression, increased I SOC, enhanced CCE, and elevated [Ca2+]cyt may play important roles in mediating bronchial constriction and BSMC proliferation.


2014 ◽  
Vol 306 (4) ◽  
pp. H574-H584 ◽  
Author(s):  
Jack Rubinstein ◽  
Valerie M. Lasko ◽  
Sheryl E. Koch ◽  
Vivek P. Singh ◽  
Vinicius Carreira ◽  
...  

Transient receptor potential cation channels have been implicated in the regulation of cardiovascular function, but only recently has our laboratory described the vanilloid-2 subtype (TRPV2) in the cardiomyocyte, though its exact mechanism of action has not yet been established. This study tests the hypothesis that TRPV2 plays an important role in regulating myocyte contractility under physiological conditions. Therefore, we measured cardiac and vascular function in wild-type and TRPV2−/− mice in vitro and in vivo and found that TRPV2 deletion resulted in a decrease in basal systolic and diastolic function without affecting loading conditions or vascular tone. TRPV2 stimulation with probenecid, a relatively selective TRPV2 agonist, caused an increase in both inotropy and lusitropy in wild-type mice that was blunted in TRPV2−/− mice. We examined the mechanism of TRPV2 inotropy/lusitropy in isolated myocytes and found that it modulates Ca2+ transients and sarcoplasmic reticulum Ca2+ loading. We show that the activity of this channel is necessary for normal cardiac function and that there is increased contractility in response to agonism of TRPV2 with probenecid.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 334
Author(s):  
Huilong Luo ◽  
Xavier Declèves ◽  
Salvatore Cisternino

The gliovascular unit (GVU) is composed of the brain microvascular endothelial cells forming blood–brain barrier and the neighboring surrounding “mural” cells (e.g., pericytes) and astrocytes. Modulation of the GVU/BBB features could be observed in a variety of vascular, immunologic, neuro-psychiatric diseases, and cancers, which can disrupt the brain homeostasis. Ca2+ dynamics have been regarded as a major factor in determining BBB/GVU properties, and previous studies have demonstrated the role of transient receptor potential vanilloid (TRPV) channels in modulating Ca2+ and BBB/GVU properties. The physiological role of thermosensitive TRPV channels in the BBB/GVU, as well as their possible therapeutic potential as targets in treating brain diseases via preserving the BBB are reviewed. TRPV2 and TRPV4 are the most abundant isoforms in the human BBB, and TRPV2 was evidenced to play a main role in regulating human BBB integrity. Interspecies differences in TRPV2 and TRPV4 BBB expression complicate further preclinical validation. More studies are still needed to better establish the physiopathological TRPV roles such as in astrocytes, vascular smooth muscle cells, and pericytes. The effect of the chronic TRPV modulation should also deserve further studies to evaluate their benefit and innocuity in vivo.


Author(s):  
Sanjeev K. Singh ◽  
M. S. Muthu ◽  
Ravindran Revand ◽  
M. B. Mandal

Background: Since long back, it has been a matter of discussion regarding the role of peripheral blood vessels in regulation of cardiorespiratory (CVR) system. Objective: The role of 5-HT3 and TRPV1 receptors present on perivascular nerves in elicitation of CVR reflexes was examined after intra-arterial instillation of bradykinin in urethane anesthetized rats. Materials and Methods: Femoral artery was cannulated retrogradely and was utilized for the instillation of saline/agonist/antagonist and recording of blood pressure (BP), using a double ported 24G cannula. BP, respiration and ECG were recorded for 30 min after bradykinin (1 µM) in the absence or presence of antagonists. Results: Instillation of bradykinin produced immediate hypotensive (40%), bradycardiac (17%), tachypnoeic (45%) and hyperventilatory (96%) responses of shorter latencies (5-8 s) favoring the neural mechanisms in producing the responses. In lignocaine (2%) pretreated animals, bradykinin-induced hypotensive (10%), bradycardiac (1.7%), tachypnoeic (13%) and hyperventilatory (13%) responses attenuated significantly. Pretreatment with ondansetron (100 µg/kg), 5-HT3-antagonist attenuated the hypotensive (10%), bradycardiac (1.7%), tachypnoeic (11%) and hyperventilatory (11%) responses significantly. Pretreatment with capsazepine (1 mg/kg), transient receptor potential vanilloid 1- antagonist blocked the hypotensive (5%), bradycardiac (1.2%), tachypnoeic (6%) and hyperventilatory (6%) responses significantly. Conclusion: In conclusion, presence of a nociceptive agent in the local segment of an artery evokes vasosensory reflex responses modulating CVR parameters involving TRPV1 and 5-HT3 receptors present on the perivascular sensory nerve terminals in anesthetized rats.


Sign in / Sign up

Export Citation Format

Share Document