Mechanisms underlying capsaicin effects in canine coronary artery: implications for coronary spasm

Hiett, S. Christopher; Owen, Meredith K.; Li, Wennan; Chen, Xingjuan; Riley, Ashley M.; Noblet, Jillian N.; Flores, Sarah; Sturek, Michael; Tune, Johnathan D.; Obukhov, Alexander G.

doi:10.1093/cvr/cvu152

Cited by 14 publications

(18 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The most common clinical signs were gastrointestinal (76%, emesis and anorexia) and neurological (63%, depression). This is in agreement with another study that showed a high number of patients poisoned by medications leading to severe gastrointestinal clinical signs [10]. Our findings may be explained by the prevalence of poisoning route (63% oral and 30% cutaneous).…”

Section: Discussionsupporting

confidence: 93%

A Retrospective Study of Small Animal Poisoning at the Veterinary Medical Teaching Hospital from South Region of Brazil

Zang

Bing

Araújo

et al. 2018

Acta Scientiae. Vet.

View full text Add to dashboard Cite

Background: Poisoning cases are a challenge for the veterinary practitioner, since many agents can be involved. The incomplete patient history associated with advanced poisoning stage often leads to death. Since lacking information is common, it is essential to be aware of principal poisoning agents and their associated symptomatology. The aim of this study is to describe the major agents involved in small animal poisoning, the causative agent, poisoning route, time to search veterinary care, clinical signs and ancillary tests of canine and feline patients treated at the Veterinary Medical Teaching Hospital from January 2010 to June 2016. Materials, Methods & Results:Forty-four medical records with poisoning history were found and reviewed, but only 30 medical records had complete data to be evaluated. There were 24 dogs and 6 cats, 17 female and 13 male. Six females were spayed. Poisoning agent identification was possible in 29 cases and was food, molluscicide, cleaning product, ornamental plants, medication, rodenticide and antiparasitic drugs. Fourteen poisonings were caused by the owner and 16 were accidental. There was a higher poisoning incidence in dogs than cats. Most of the patients were young and unneutered/unspayed. Discussion: In this study there was a higher poisoning prevalence in dogs than cats, as occurred in other studies published in Europe, Belgium, France, Greece, Italy, Spain, Austria and other Brazilian regions. Most of the patients were young, which is in agreement with previous studies in which young animals were more affected. Domestic antiparasitic drugs were the most common poisoning agents (33%), as reported in studies from France and Spain. In southern Brazil, the most common poisoning agent was medication, whereas in southeast Brazil, organophosphates were the most prevalent poisoning agent. Considering this, the geographic localisation seems to influence the poisoning agent. It is known that many owners give unprescribed medication to their pets and this also happened in this study, as 46% of the poisoning cases were caused by the owner. The most common clinical signs were gastrointestinal (76%, emesis and anorexia) and neurological (63%, depression). This is in agreement with another study that showed a high number of patients poisoned by medications leading to severe gastrointestinal clinical signs. Despite a history of eating spiced food, our food-poisoned patient did not show clinical signs compatible with pepper poisoning. In fact, clinical signs were more compatible with salt or onion and garlic poisoning, but there was no history to support that our patient had eaten these foods. The patient who ate fern and busy Lizzie (Impatiens walleriana) did not show clinical signs compatible with these agents but showed gastrointestinal clinical signs that could have occurred due to plant indigestion. This fact emphasises the need for more studies in this area. One dog with rodenticide poisoning presented with normal blood test results, but the blood sample was collected a few hours aft...

show abstract

Section: Discussionsupporting

confidence: 93%

A Retrospective Study of Small Animal Poisoning at the Veterinary Medical Teaching Hospital from South Region of Brazil

Zang

Bing

Araújo

et al. 2018

Acta Scientiae. Vet.

View full text Add to dashboard Cite

show abstract

“…Isolated coronary arteries were cut into 2–3 mm rings and mounted in the organ baths containing Krebs solution saturated with a gas mixture of 95% O 2 and 5% CO 2 at 37 °C. The optimal length was determined as described elsewhere [ 8 , 11 , 24 ]. This usually resulted in a preload value of ~3 g. Both KCl and histamine were added directly to the organ baths.…”

Section: Methodsmentioning

confidence: 99%

Long-term spironolactone treatment reduces coronary TRPC expression, vasoconstriction, and atherosclerosis in metabolic syndrome pigs

Chen

Riley

et al. 2017

Basic Res Cardiol

Self Cite

View full text Add to dashboard Cite

Coronary transient receptor potential canonical (TRPC) channel expression is elevated in metabolic syndrome (MetS). However, differential contribution of TRPCs to coronary pathology in MetS is not fully elucidated. We investigated the roles of TRPC1 and TRPC6 isoforms in coronary arteries of MetS pigs and determined whether long-term treatment with a mineralocorticoid receptor inhibitor, spironolactone, attenuates coronary TRPC expression and associated dysfunctions. MetS coronary arteries exhibited significant atherosclerosis, endothelial dysfunction, and increased histamine-induced contractions. Immunohistochemical studies revealed that TRPC6 immunostaining was significantly greater in the medial layer of MetS pig coronary arteries compared to that in Lean pigs, whereas little TRPC6 immunostaining was found in atheromas. Conversely, TRPC1 immunostaining was weak in the medial layer but strong in MetS atheromas, where it was predominantly localized to macrophages. Spironolactone treatment significantly decreased coronary TRPC expression and dysfunctions in MetS pigs. In vivo targeted delivery of the dominant-negative (DN)-TRPC6 cDNA to the coronary wall reduced histamine-induced calcium transients in the MetS coronary artery medial layer, implying a role for TRPC6 in mediating calcium influx in MetS coronary smooth muscles. Monocyte adhesion was increased in Lean pig coronary arteries cultured in the presence of aldosterone; and spironolactone antagonized this effect, suggesting that coronary mineralocorticoid receptor activation may regulate macrophage infiltration. TRPC1 expression in atheroma macrophages was associated with advanced atherosclerosis, whereas medial TRPC6 upregulation correlated with increased histamine-induced calcium transients and coronary contractility. We propose that long-term spironolactone treatment may be a therapeutic strategy to decrease TRPC expression and coronary pathology associated with MetS.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-017-0643-0) contains supplementary material, which is available to authorized users.

show abstract

“…The right CAs (RCAs) with a diameter of about 1–2 mm were cut into 2–3 mm rings. The isometric tension experiments were performed as described previously [ 24 , 25 ]. Briefly, the rings were mounted into organ baths containing oxygenated (saturated with a gas mixture of 95% O 2 and 5% CO 2 ) Krebs buffer that was maintained at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Novel Roles for Kv7 Channels in Shaping Histamine-Induced Contractions and Bradykinin-Dependent Relaxations in Pig Coronary Arteries

Chen

Hiett

et al. 2016

PLoS ONE

Self Cite

View full text Add to dashboard Cite

Voltage-gated Kv7 channels are inhibited by agonists of Gq-protein-coupled receptors, such as histamine. Recent works have provided evidence that inhibition of vascular Kv7 channels may trigger vessel contractions. In this study, we investigated how Kv7 activity modulates the histamine-induced contractions in “healthy” and metabolic syndrome (MetS) pig right coronary arteries (CAs). We performed isometric tension and immunohistochemical studies with domestic, lean Ossabaw, and MetS Ossabaw pig CAs. We found that neither the Kv7.2/Kv7.4/Kv7.5 activator ML213 nor the general Kv7 inhibitor XE991 altered the tension of CA rings under preload, indicating that vascular Kv7 channels are likely inactive in the preloaded rings. Conversely, ML213 potently dilated histamine-pre-contracted CAs, suggesting that Kv7 channels are activated during histamine applications and yet partially inhibited by histamine. Immunohistochemistry analysis revealed strong Kv7.4 immunostaining in the medial and intimal layers of the CA wall, whereas Kv7.5 immunostaining intensity was strong in the intimal but weak in the medial layers. The medial Kv7 immunostaining was significantly weaker in MetS Ossabaw CAs as compared to lean Ossabaw or domestic CAs. Consistently, histamine-pre-contracted MetS Ossabaw CAs exhibited attenuated ML213-dependent dilations. In domestic pig CAs, where medial Kv7 immunostaining intensity was stronger, histamine-induced contractions spontaneously decayed to ~31% of the peak amplitude within 4 minutes. Oppositely, in Ossabaw CAs, where Kv7 immunostaining intensity was weaker, the histamine-induced contractions were more sustained. XE991 pretreatment significantly slowed the decay rate of histamine-induced contractions in domestic CAs, supporting the hypothesis that increased Kv7 activity correlates with a faster rate of histamine-induced contraction decay. Alternatively, XE991 significantly decreased the amplitude of bradykinin-dependent dilations in pre-contracted CAs. We propose that in CAs, a decreased expression or a loss of function of Kv7 channels may lead to sustained histamine-induced contractions and reduced endothelium-dependent relaxation, both risk factors for coronary spasm.

show abstract

Mechanisms underlying capsaicin effects in canine coronary artery: implications for coronary spasm

Abstract: Capsaicin alone does not cause contractions in conduit canine coronary artery; however, pre-treatment with pro-inflammatory prostaglandin-thromboxane agonists may unmask capsaicin's vasoconstrictive potential.

Cited by 14 publications

References 42 publications

A Retrospective Study of Small Animal Poisoning at the Veterinary Medical Teaching Hospital from South Region of Brazil

A Retrospective Study of Small Animal Poisoning at the Veterinary Medical Teaching Hospital from South Region of Brazil

Long-term spironolactone treatment reduces coronary TRPC expression, vasoconstriction, and atherosclerosis in metabolic syndrome pigs

Novel Roles for Kv7 Channels in Shaping Histamine-Induced Contractions and Bradykinin-Dependent Relaxations in Pig Coronary Arteries

Contact Info

Product

Resources

About