Activity and expression of the vanilloid receptor 1 (TRPV1) is altered by long‐term diabetes in epineurial arterioles of the rat sciatic nerve

Davidson, Eric P.; Coppey, Lawrence J.; Yorek, Mark A.

doi:10.1002/dmrr.599

Cited by 22 publications

(21 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6,20,21 DM might interfere with the expression of TRPV1 as several investigations have found that the expression of TRPV1 in DRG and epineurial arterioles was decreased in diabetic animals. 9,10 In the previous and present study, we disclosed in each that the expression of both TRPV1 and CGRP in diabetic mouse hearts is markedly reduced in comparison with that in the non-diabetic hearts, implying that the function of TRPV1 in the heart was impaired by diabetes.…”

Section: Discussionsupporting

confidence: 55%

“…9 Using immunohistochemical staining, TRPV1 was also found to be reduced in epineurial arterioles in long-term diabetic rats. 10 These investigations suggest that the expression of TRPV1 is susceptible to diabetes. In addition, recent studies disclose that TRPV1 is expressed in the myocardium and perivascular region, which are close to the epicardial surface of ventricles.…”

mentioning

confidence: 97%

See 1 more Smart Citation

Decreased Expression of Transient Receptor Potential Vanilloid 1 Impaires the Postischemic Recovery of Diabetic Mouse Hearts

Wei

Wang

Han

et al. 2009

Circ J

View full text Add to dashboard Cite

iabetes mellitus (DM) is one of the most important risk factors of cardiovascular diseases, and numerous patients who are afflicted with diabetes usually suffer the diffused stenosis of coronary arteries, leading to dreadful consequences such as myocardial infarction and cardiomyopathy. Non-invasive evaluation tools such as Doppler echocardiography demonstrate the impairment of cardiac function in diabetic animal models as well as in diabetic patients, 1,2 whereas the mechanism is still not well elucidated.Neuropathy is one of the common complications of diabetes, which could result in the degeneration of the nerve fibers both in diabetic animals and patients. 3-5 Transient Receptor Potential Vanilloid 1 (TRPV1) is a non-selective cation channel and is diversely distributed in terminals of sensory nerve fibers, dorsal root ganglia (DRG), spinal cord, and many other various regions in the brain. 6 It could lead to the release of neurotransmitters such as calcitonin generelated peptide (CGRP) from peripheral nerve terminals when activated by capsaicin, protons, noxious heat, etc. 7,8 It has been found that in diabetes-prone NOD mice, the protein expression and function of TRPV1 was significantly depressed in DRG. 9 Using immunohistochemical staining, TRPV1 was also found to be reduced in epineurial arterioles in long-term diabetic rats. 10 These investigations suggest that the expression of TRPV1 is susceptible to diabetes. In addition, recent studies disclose that TRPV1 is expressed in the myocardium and perivascular region, which are close to the epicardial surface of ventricles. 11 We revealed that the expression of TRPV1 in diabetic hearts was significantly suppressed in our previous study. 12 However, the impact of the decreased TRPV1 on the diabetic heart has not been investigated yet.A few studies have revealed that TRPV1 can serve as a molecular integrator of various noxious stimuli, especially the myocardial ischemia, in order to protect the hearts against ischemic injury. 11,13 For example, exogenous agonists of TRPV1 exert a cardioprotective effect on ischemia/reperfusion injury, whereas TRPV1 gene knockout eliminates the protection. 14,15 Therefore, it is reasonable to hypothesize that the alteration of TRPV1 secondary to diabetes can be related to the severe postischemic injury of the heart.In the present study, we measure the expression of TRPV1 and CGRP in diabetic hearts and investigate the effect of TRPV1 on the cardiac function after ischemia injury. The results might help explain the vulnerability of diabetic hearts to ischemic injury.

show abstract

Section: Discussionsupporting

confidence: 55%

mentioning

confidence: 97%

Decreased Expression of Transient Receptor Potential Vanilloid 1 Impaires the Postischemic Recovery of Diabetic Mouse Hearts

Wei

Wang

Han

et al. 2009

Circ J

View full text Add to dashboard Cite

show abstract

“…Decreased TRPV1 expression in diabetic animals has been previously reported (7). However, the impact of decreased TRPV1 channel expression on the diabetic heart has not been thoroughly investigated.…”

Section: H221 Vascular Trpv1 Channels In Type II Diabetesmentioning

confidence: 92%

“…We and others (1,3,7,10,31,41,43) have revealed TRP channel expression in vascular smooth muscle cells (VSMC) and endothelial cells (EC) suggesting these channels regulate vascular functions. Specifically, we found that TRPV1 channels play an important role in the vascular reactivity, largely through Ca 2ϩ entry via endothelial TRPV1 channels, triggering nitric oxide (NO)-dependent vasodilation in endothelium of conduit coronary arteries from Ossabaw swine (3).…”

mentioning

confidence: 97%

Disruption of TRPV1-mediated coupling of coronary blood flow to cardiac metabolism in diabetic mice: role of nitric oxide and BK channels

Guarini

Ohanyan

Kmetz

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

channel-dependent coronary function is compromised in pigs with metabolic syndrome (MetS). However, the mechanisms through which TRPV1 channels couple coronary blood flow to metabolism are not fully understood. We employed mice lacking TRPV1 [TRPV1 (Ϫ/Ϫ) ], db/db diabetic, and control C57BKS/J mice to determine the extent to which TRPV1 channels modulate coronary function and contribute to vascular dysfunction in diabetic cardiomyopathy. Animals were subjected to in vivo infusion of the TRPV1 agonist capsaicin to examine the hemodynamic actions of TRPV1 activation. Capsaicin (1-100 g·kg Ϫ1 ·min Ϫ1 ) dose dependently increased coronary blood flow in control mice, which was inhibited by the TRPV1 antagonist capsazepine or the nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME). In addition, the capsaicin-mediated increase in blood flow was attenuated in db/db mice. TRPV1(Ϫ/Ϫ) mice exhibited no changes in coronary blood flow in response to capsaicin. Vasoreactivity studies in isolated pressurized mouse coronary microvessels revealed a capsaicin-dependent relaxation that was inhibited by the TRPV1 inhibitor SB366791 L-NAME and to the large conductance calcium-sensitive potassium channel (BK) inhibitors iberiotoxin and Penetrim A. Similar to in vivo responses, capsaicinmediated relaxation was impaired in db/db mice compared with controls. Changes in pH (pH 7.4 -6.0) relaxed coronary vessels contracted to the thromboxane mimetic U46619 in all three groups of mice; however, pH-mediated relaxation was blunted in vessels obtained from TRPV1 (Ϫ/Ϫ) and db/db mice compared with controls. Western blot analysis revealed decreased myocardial TRPV1 protein expression in db/db mice compared with controls. Our data reveal TRPV1 channels mediate coupling of myocardial blood flow to cardiac metabolism via a nitric oxide-dependent, BK channeldependent pathway that is corrupted in diabetes. transient receptor potential vanilloid 1 channels; capsaicin; coronary; cardiac metabolism; myocardial blood flow TYPE II DIABETES INCREASES the morbidity and mortality to many cardiovascular-related diseases, such as coronary artery disease (CAD) by as much as fourfold vs. nondiabetic patients (17,30). This is attributed in part, to a greater development of both micro-and macrovascular disease. Impaired coronary microvascular blood flow contributes to the increased cardiovascular events associated with diabetes through numerous mechanisms (27, 35). The proposed mechanism for the pathogenesis of diabetic cardiomyopathy likely reflects the multifactorial and highly complex nature of diabetes, but arterial dysfunction clearly appears to be a contributing factor.The transient receptor potential vanilloid 1 (TRPV1) channels are characteristically gated by chemical and physical stimuli including changes in pH, heat, ethanol, and endovanilloid compounds such as capsaicin (5). We and others (1,3,7,10,31,41,43) have revealed TRP channel expression in vascular smooth muscle cells (VSMC) and endothelial cells (EC) suggesting th...

show abstract

“…The precise mechanisms underlying this beneficial effect of capsaicin in diabetic patients remain to be determined. Diabetic neuropathy is known to be associated with a reduced production of CGRP, a vasoactive molecule that is under the control of TRPV1 receptors in nerve terminals, and causes neurogenic vasodilation (11). Activation of TRPV1 by capsaicin may cause an increased CGRP release, thereby restoring the blood vessel response to stimulation of sensory nerve endings (12).…”

Section: Discussionmentioning

confidence: 99%

Capsaicin restores cutaneous microcirculation in diabetes: a capillaroscopic study

Carlesimo¹

2014

CDERM

View full text Add to dashboard Cite

SummaryBackground. Capsaicin (8-methyl-N-vanyllil-6-nonenamide), the active component of the chilli peppers, is able to induce receptor desensitization and defunctionalisation of peripheral nociceptors. It can induce also vascular responses by different mechanisms. Objectives. Hypothesis that skin application of capsaicin could have beneficial effects on cutaneous microcirculatory dysfunction associated with diabetes. Materials and methods. Videocapillaroscopic examination of periungueal vascular pattern before and after application of topical capsaicin in diabetic patients. Results. Skin application of 15% capsaicin oleoresin caused a local improvement in microvascular function in diabetic patients. Conclusions. Topical capsaicin application may be beneficial for the management of microvascular complications in diabetic patients.

show abstract

Activity and expression of the vanilloid receptor 1 (TRPV1) is altered by long‐term diabetes in epineurial arterioles of the rat sciatic nerve

Abstract: These studies suggest that long-term diabetes causes vascular dysfunction in epineurial arterioles of the sciatic nerve that includes a decrease in capsaicin-induced vasoconstriction that is likely due to a decrease in the expression of vanilloid receptor 1.

Cited by 22 publications

References 30 publications

Decreased Expression of Transient Receptor Potential Vanilloid 1 Impaires the Postischemic Recovery of Diabetic Mouse Hearts

Decreased Expression of Transient Receptor Potential Vanilloid 1 Impaires the Postischemic Recovery of Diabetic Mouse Hearts

Disruption of TRPV1-mediated coupling of coronary blood flow to cardiac metabolism in diabetic mice: role of nitric oxide and BK channels

Capsaicin restores cutaneous microcirculation in diabetes: a capillaroscopic study

Contact Info

Product

Resources

About