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  1. Article ; Online: Vasorelaxation to capsaicin and its effects on calcium influx in arteries.

    Hopps, Jamie J / Dunn, William R / Randall, Michael D

    European journal of pharmacology

    2012  Volume 681, Issue 1-3, Page(s) 88–93

    Abstract: Capsaicin, an activator of the transient potential vanilloid receptor type 1 (TRPV1), is a commonly used pharmacological tool for desensitising sensory nerves. Capsaicin can induce vasorelaxation of isolated blood vessels by activating perivascular TRPV1 ...

    Abstract Capsaicin, an activator of the transient potential vanilloid receptor type 1 (TRPV1), is a commonly used pharmacological tool for desensitising sensory nerves. Capsaicin can induce vasorelaxation of isolated blood vessels by activating perivascular TRPV1 receptors, causing the release of vasoactive neuropeptides. This study attempted to characterise the vascular effects of capsaicin in the rat isolated aorta and porcine coronary arteries. Capsaicin elicited concentration-dependent vasorelaxation of both rat aortae and porcine coronary arteries. Capsaicin-induced vasorelaxation of rat aorta was unaffected by a chronic pre-treatment of vessels with capsaicin. Moreover, relaxation was insensitive to the presence of capsazepine, a competitive TRPV1 antagonist, in both the rat aorta and porcine coronary artery. It was hypothesised that capsaicin may be inhibiting calcium influx into smooth muscle cells. Indeed, in vessels incubated in a Ca²⁺-free high-k⁺ buffer, the presence of 30 μM capsaicin significantly inhibited the contractile response to the re-introduction of Ca²⁺. In porcine coronary arteries 100 μM capsaicin completely abolished the contractile response to the re-introduction of Ca²⁺. In addition, capsaicin also abolished the concentration-dependent contraction of porcine coronary arteries induced by the L-type calcium activator Bay-K 8644. Therefore, we suggest that capsaicin causes vascular responses in arteries through the inhibition of L-type Ca²⁺ channels. In summary,we have identified a potential mechanism underlying TRPV1-independent capsaicin-induced vasorelaxation. Our results also question the use of chronic capsaicin pre-treatment in experimental pharmacology in order to elucidate the role of sensory nerves in vascular responses.
    MeSH term(s) 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/pharmacology ; Animals ; Aorta, Abdominal/drug effects ; Aorta, Abdominal/metabolism ; Calcium/metabolism ; Calcium Channel Blockers/administration & dosage ; Calcium Channel Blockers/pharmacology ; Calcium Channels, L-Type/drug effects ; Calcium Channels, L-Type/metabolism ; Capsaicin/administration & dosage ; Capsaicin/analogs & derivatives ; Capsaicin/pharmacology ; Coronary Vessels/drug effects ; Coronary Vessels/metabolism ; Dose-Response Relationship, Drug ; Male ; Rats ; Rats, Wistar ; Swine ; TRPV Cation Channels/antagonists & inhibitors ; Vasodilation/drug effects
    Chemical Substances Calcium Channel Blockers ; Calcium Channels, L-Type ; TRPV Cation Channels ; Trpv1 protein, rat ; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester (71145-03-4) ; capsazepine (LFW48MY844) ; Capsaicin (S07O44R1ZM) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2012-02-21
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 80121-5
    ISSN 1879-0712 ; 0014-2999
    ISSN (online) 1879-0712
    ISSN 0014-2999
    DOI 10.1016/j.ejphar.2012.02.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Enhanced vasorelaxant effects of the endocannabinoid-like mediator, oleamide, in hypertension.

    Hopps, Jamie J / Dunn, William R / Randall, Michael D

    European journal of pharmacology

    2012  Volume 684, Issue 1-3, Page(s) 102–107

    Abstract: Oleamide is an endocannabinoid-like, fatty acid amide with structural similarities to anandamide. The cardiovascular effects of anandamide are enhanced in hypertension and we have now examined how hypertension affects responses to oleamide. Vasorelaxant ... ...

    Abstract Oleamide is an endocannabinoid-like, fatty acid amide with structural similarities to anandamide. The cardiovascular effects of anandamide are enhanced in hypertension and we have now examined how hypertension affects responses to oleamide. Vasorelaxant responses to oleamide were significantly (P<0.001) enhanced in aortic rings from spontaneously hypertensive rats (SHRs), such that the maximal relaxation to oleamide was 40.3 ± 3.5%, compared to 15.7 ± 3.9% in normotensive Wistar Kyoto (WKY) controls. The augmented responses to oleamide in SHR arteries were unaffected by either inhibition of nitric oxide synthase (300 μM l-NAME) or fatty acid amide hydrolase (1 μM URB597) and independent of cannabinoid CB(1) receptors or the endothelium. The enhanced responses to oleamide were opposed by pre-treatment with capsaicin (such that R(max) was reduced to 9.8 ± 1.5%) and this occurred independently of TRPV1 receptor and sensory nerve activity, as the TRPV1 antagonist capsazepine (1-5 μM) and the cation channel inhibitor ruthenium red (10 μM) had no effect on the responses to oleamide. However, inhibition of cyclooxygenase (10 μM indomethacin) enhanced the responses in the WKY aortae, such that the responses were comparable to those in the SHR. The results suggest that the cyclooxygenase pathway has a role in modulating vasorelaxation caused by oleamide in normotensive aortae and that this is lost in hypertension, possibly as an adaptation to the increase in blood pressure.
    MeSH term(s) Amidohydrolases/antagonists & inhibitors ; Animals ; Aorta/drug effects ; Aorta/metabolism ; Aorta/physiopathology ; Benzamides/pharmacology ; Biomimetic Materials/pharmacology ; Cannabinoid Receptor Modulators/metabolism ; Capsaicin/analogs & derivatives ; Capsaicin/pharmacology ; Carbamates/pharmacology ; Cyclooxygenase Inhibitors/pharmacology ; Endocannabinoids ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism ; Hypertension/drug therapy ; Hypertension/metabolism ; Hypertension/physiopathology ; In Vitro Techniques ; Male ; NG-Nitroarginine Methyl Ester/pharmacology ; Oleic Acids/pharmacology ; Rats ; Receptor, Cannabinoid, CB1/metabolism ; TRPV Cation Channels/antagonists & inhibitors ; Vasodilator Agents/pharmacology ; Vasodilator Agents/therapeutic use
    Chemical Substances Benzamides ; Cannabinoid Receptor Modulators ; Carbamates ; Cyclooxygenase Inhibitors ; Endocannabinoids ; Oleic Acids ; Receptor, Cannabinoid, CB1 ; TRPV Cation Channels ; Trpv1 protein, rat ; Vasodilator Agents ; cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester ; oleylamide (7L25QK8BWO) ; Amidohydrolases (EC 3.5.-) ; fatty-acid amide hydrolase (EC 3.5.1.-) ; capsazepine (LFW48MY844) ; Capsaicin (S07O44R1ZM) ; NG-Nitroarginine Methyl Ester (V55S2QJN2X)
    Language English
    Publishing date 2012-06-05
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80121-5
    ISSN 1879-0712 ; 0014-2999
    ISSN (online) 1879-0712
    ISSN 0014-2999
    DOI 10.1016/j.ejphar.2012.03.027
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article: Vasorelaxation to capsaicin and its effects on calcium influx in arteries

    Hopps, Jamie J / Dunn, William R / Randall, Michael D

    European journal of pharmacology. 2012 Apr. 15, v. 681, no. 1-3

    2012  

    Abstract: Capsaicin, an activator of the transient potential vanilloid receptor type 1 (TRPV1), is a commonly used pharmacological tool for desensitising sensory nerves. Capsaicin can induce vasorelaxation of isolated blood vessels by activating perivascular TRPV1 ...

    Abstract Capsaicin, an activator of the transient potential vanilloid receptor type 1 (TRPV1), is a commonly used pharmacological tool for desensitising sensory nerves. Capsaicin can induce vasorelaxation of isolated blood vessels by activating perivascular TRPV1 receptors, causing the release of vasoactive neuropeptides. This study attempted to characterise the vascular effects of capsaicin in the rat isolated aorta and porcine coronary arteries. Capsaicin elicited concentration-dependent vasorelaxation of both rat aortae and porcine coronary arteries. Capsaicin-induced vasorelaxation of rat aorta was unaffected by a chronic pre-treatment of vessels with capsaicin. Moreover, relaxation was insensitive to the presence of capsazepine, a competitive TRPV1 antagonist, in both the rat aorta and porcine coronary artery. It was hypothesised that capsaicin may be inhibiting calcium influx into smooth muscle cells. Indeed, in vessels incubated in a Ca²⁺-free high-k⁺ buffer, the presence of 30μM capsaicin significantly inhibited the contractile response to the re-introduction of Ca²⁺. In porcine coronary arteries 100μM capsaicin completely abolished the contractile response to the re-introduction of Ca²⁺. In addition, capsaicin also abolished the concentration-dependent contraction of porcine coronary arteries induced by the L-type calcium activator Bay-K 8644. Therefore, we suggest that capsaicin causes vascular responses in arteries through the inhibition of L-type Ca²⁺ channels. In summary, we have identified a potential mechanism underlying TRPV1-independent capsaicin-induced vasorelaxation. Our results also question the use of chronic capsaicin pre-treatment in experimental pharmacology in order to elucidate the role of sensory nerves in vascular responses.
    Keywords antagonists ; aorta ; calcium ; capsaicin ; coronary vessels ; myocytes ; nerve tissue ; neuropeptides ; pharmacology ; pretreatment ; rats ; receptors ; smooth muscle ; swine ; vasodilation
    Language English
    Dates of publication 2012-0415
    Size p. 88-93.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 80121-5
    ISSN 1879-0712 ; 0014-2999
    ISSN (online) 1879-0712
    ISSN 0014-2999
    DOI 10.1016/j.ejphar.2012.02.019
    Database NAL-Catalogue (AGRICOLA)

    More links

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  4. Article: Enhanced vasorelaxant effects of the endocannabinoid-like mediator, oleamide, in hypertension

    Hopps, Jamie J / Dunn, William R / Randall, Michael D

    European journal of pharmacology. 2012 June 5, v. 684, no. 1-3

    2012  

    Abstract: Oleamide is an endocannabinoid-like, fatty acid amide with structural similarities to anandamide. The cardiovascular effects of anandamide are enhanced in hypertension and we have now examined how hypertension affects responses to oleamide. Vasorelaxant ... ...

    Abstract Oleamide is an endocannabinoid-like, fatty acid amide with structural similarities to anandamide. The cardiovascular effects of anandamide are enhanced in hypertension and we have now examined how hypertension affects responses to oleamide. Vasorelaxant responses to oleamide were significantly (P<0.001) enhanced in aortic rings from spontaneously hypertensive rats (SHRs), such that the maximal relaxation to oleamide was 40.3±3.5%, compared to 15.7±3.9% in normotensive Wistar Kyoto (WKY) controls. The augmented responses to oleamide in SHR arteries were unaffected by either inhibition of nitric oxide synthase (300μM l-NAME) or fatty acid amide hydrolase (1μM URB597) and independent of cannabinoid CB₁ receptors or the endothelium. The enhanced responses to oleamide were opposed by pre-treatment with capsaicin (such that Rₘₐₓ was reduced to 9.8±1.5%) and this occurred independently of TRPV1 receptor and sensory nerve activity, as the TRPV1 antagonist capsazepine (1–5μM) and the cation channel inhibitor ruthenium red (10μM) had no effect on the responses to oleamide. However, inhibition of cyclooxygenase (10μM indomethacin) enhanced the responses in the WKY aortae, such that the responses were comparable to those in the SHR. The results suggest that the cyclooxygenase pathway has a role in modulating vasorelaxation caused by oleamide in normotensive aortae and that this is lost in hypertension, possibly as an adaptation to the increase in blood pressure.
    Keywords antagonists ; arteries ; blood pressure ; cannabinoids ; capsaicin ; endothelium ; fatty acids ; hypertension ; indomethacin ; nerve tissue ; nitric oxide synthase ; pretreatment ; prostaglandin synthase ; rats ; receptors ; ruthenium ; vasodilation
    Language English
    Dates of publication 2012-0605
    Size p. 102-107.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 80121-5
    ISSN 1879-0712 ; 0014-2999
    ISSN (online) 1879-0712
    ISSN 0014-2999
    DOI 10.1016/j.ejphar.2012.03.027
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

  5. Article: Enhanced vasorelaxant effects of the endocannabinoid-like mediator, oleamide, in hypertension

    Hopps, Jamie J. / Dunn, William R. / Randall, Michael D.

    European journal of pharmacology

    Volume v. 684,, Issue no. 1

    Abstract: Oleamide is an endocannabinoid-like, fatty acid amide with structural similarities to anandamide. The cardiovascular effects of anandamide are enhanced in hypertension and we have now examined how hypertension affects responses to oleamide. Vasorelaxant ... ...

    Abstract Oleamide is an endocannabinoid-like, fatty acid amide with structural similarities to anandamide. The cardiovascular effects of anandamide are enhanced in hypertension and we have now examined how hypertension affects responses to oleamide. Vasorelaxant responses to oleamide were significantly (P<0.001) enhanced in aortic rings from spontaneously hypertensive rats (SHRs), such that the maximal relaxation to oleamide was 40.3±3.5%, compared to 15.7±3.9% in normotensive Wistar Kyoto (WKY) controls. The augmented responses to oleamide in SHR arteries were unaffected by either inhibition of nitric oxide synthase (300μM l-NAME) or fatty acid amide hydrolase (1μM URB597) and independent of cannabinoid CB₁ receptors or the endothelium. The enhanced responses to oleamide were opposed by pre-treatment with capsaicin (such that Rₘₐₓ was reduced to 9.8±1.5%) and this occurred independently of TRPV1 receptor and sensory nerve activity, as the TRPV1 antagonist capsazepine (1–5μM) and the cation channel inhibitor ruthenium red (10μM) had no effect on the responses to oleamide. However, inhibition of cyclooxygenase (10μM indomethacin) enhanced the responses in the WKY aortae, such that the responses were comparable to those in the SHR. The results suggest that the cyclooxygenase pathway has a role in modulating vasorelaxation caused by oleamide in normotensive aortae and that this is lost in hypertension, possibly as an adaptation to the increase in blood pressure.
    Keywords endothelium ; indomethacin ; fatty acids ; blood pressure ; receptors ; antagonists ; nitric oxide synthase ; vasodilation ; cannabinoids ; nerve tissue ; pretreatment ; capsaicin ; hypertension ; ruthenium ; rats ; prostaglandin synthase ; arteries
    Language English
    Document type Article
    ISSN 0014-2999
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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    Kategorien

  6. Article: Vasorelaxation to capsaicin and its effects on calcium influx in arteries

    Hopps, Jamie J. / Dunn, William R. / Randall, Michael D.

    European journal of pharmacology

    Volume v. 681,, Issue no. 1

    Abstract: Capsaicin, an activator of the transient potential vanilloid receptor type 1 (TRPV1), is a commonly used pharmacological tool for desensitising sensory nerves. Capsaicin can induce vasorelaxation of isolated blood vessels by activating perivascular TRPV1 ...

    Abstract Capsaicin, an activator of the transient potential vanilloid receptor type 1 (TRPV1), is a commonly used pharmacological tool for desensitising sensory nerves. Capsaicin can induce vasorelaxation of isolated blood vessels by activating perivascular TRPV1 receptors, causing the release of vasoactive neuropeptides. This study attempted to characterise the vascular effects of capsaicin in the rat isolated aorta and porcine coronary arteries. Capsaicin elicited concentration-dependent vasorelaxation of both rat aortae and porcine coronary arteries. Capsaicin-induced vasorelaxation of rat aorta was unaffected by a chronic pre-treatment of vessels with capsaicin. Moreover, relaxation was insensitive to the presence of capsazepine, a competitive TRPV1 antagonist, in both the rat aorta and porcine coronary artery. It was hypothesised that capsaicin may be inhibiting calcium influx into smooth muscle cells. Indeed, in vessels incubated in a Ca²⁺-free high-k⁺ buffer, the presence of 30μM capsaicin significantly inhibited the contractile response to the re-introduction of Ca²⁺. In porcine coronary arteries 100μM capsaicin completely abolished the contractile response to the re-introduction of Ca²⁺. In addition, capsaicin also abolished the concentration-dependent contraction of porcine coronary arteries induced by the L-type calcium activator Bay-K 8644. Therefore, we suggest that capsaicin causes vascular responses in arteries through the inhibition of L-type Ca²⁺ channels. In summary, we have identified a potential mechanism underlying TRPV1-independent capsaicin-induced vasorelaxation. Our results also question the use of chronic capsaicin pre-treatment in experimental pharmacology in order to elucidate the role of sensory nerves in vascular responses.
    Keywords calcium ; smooth muscle ; neuropeptides ; antagonists ; receptors ; vasodilation ; pharmacology ; nerve tissue ; pretreatment ; capsaicin ; coronary vessels ; rats ; swine ; aorta ; myocytes
    Language English
    Document type Article
    ISSN 0014-2999
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

    More links

    Kategorien

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