Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You and Your Team.

Learn More →

Heterogeneity in the mechanisms of vasorelaxation to anandamide in resistance and conduit rat mesenteric arteries

Heterogeneity in the mechanisms of vasorelaxation to anandamide in resistance and conduit rat... In order to address mechanistic differences between arterial vessel types, we have compared the vasorelaxant actions of anandamide in resistance (G3) and conduit (G0) mesenteric arteries. Anandamide produced concentration‐dependent relaxations of pre‐constricted G3 arteries with a maximal response that was significantly greater than seen in G0. The CB1 receptor selective antagonists SR141716A (100 nM) and AM251 (100 nM) caused reductions in the vasorelaxant responses to anandamide in both arteries. Maximal vasorelaxant responses to anandamide were reduced in both arteries after treatment with capsaicin to deplete sensory neurotransmitters (10 μM for 1 h). Vasorelaxation to anandamide was not affected by the nitric oxide synthase inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME, 300 μM) in either artery. Only responses in G3 arteries were sensitive to removal of the endothelium. In G3 vessels only, vasorelaxation to anandamide was reduced by inhibition of EDHF activity with a combination of charybdotoxin (100 nM) and apamin (500 nM) in the presence of L‐NAME (300 μM) and indomethacin (10 μM). Antagonism of the novel endothelial cannabinoid receptor (O‐1918, 1 μM) caused a reduction in the sensitivity to anandamide in G3 but not G0. G3, but not G0, vessels showed a small reduction in vasorelaxant responses to anandamide after inhibition of gap junctional communication with 18α‐GA (100 μM). These results demonstrate that there are differences in the mechanisms of vasorelaxation to anandamide between conduit and resistance mesenteric arteries. In small resistance vessels, vasorelaxation occurs through stimulation of vanilloid receptors, CB1 receptors, and an endothelial receptor coupled to EDHF release. By contrast, in the larger mesenteric artery, vasorelaxation is almost entirely due to stimulation of vanilloid receptors and CB1 receptors, and is endothelium‐independent. British Journal of Pharmacology (2004) 142, 435–442. doi:10.1038/sj.bjp.0705810 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

Heterogeneity in the mechanisms of vasorelaxation to anandamide in resistance and conduit rat mesenteric arteries

Download PDF
8 pages
Read Article

Loading next page...
 
/lp/wiley/heterogeneity-in-the-mechanisms-of-vasorelaxation-to-anandamide-in-enHlPy71OS
Publisher
Wiley
Copyright
2004 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1038/sj.bjp.0705810
pmid
15148250
Publisher site
See Article on Publisher Site

Abstract

In order to address mechanistic differences between arterial vessel types, we have compared the vasorelaxant actions of anandamide in resistance (G3) and conduit (G0) mesenteric arteries. Anandamide produced concentration‐dependent relaxations of pre‐constricted G3 arteries with a maximal response that was significantly greater than seen in G0. The CB1 receptor selective antagonists SR141716A (100 nM) and AM251 (100 nM) caused reductions in the vasorelaxant responses to anandamide in both arteries. Maximal vasorelaxant responses to anandamide were reduced in both arteries after treatment with capsaicin to deplete sensory neurotransmitters (10 μM for 1 h). Vasorelaxation to anandamide was not affected by the nitric oxide synthase inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME, 300 μM) in either artery. Only responses in G3 arteries were sensitive to removal of the endothelium. In G3 vessels only, vasorelaxation to anandamide was reduced by inhibition of EDHF activity with a combination of charybdotoxin (100 nM) and apamin (500 nM) in the presence of L‐NAME (300 μM) and indomethacin (10 μM). Antagonism of the novel endothelial cannabinoid receptor (O‐1918, 1 μM) caused a reduction in the sensitivity to anandamide in G3 but not G0. G3, but not G0, vessels showed a small reduction in vasorelaxant responses to anandamide after inhibition of gap junctional communication with 18α‐GA (100 μM). These results demonstrate that there are differences in the mechanisms of vasorelaxation to anandamide between conduit and resistance mesenteric arteries. In small resistance vessels, vasorelaxation occurs through stimulation of vanilloid receptors, CB1 receptors, and an endothelial receptor coupled to EDHF release. By contrast, in the larger mesenteric artery, vasorelaxation is almost entirely due to stimulation of vanilloid receptors and CB1 receptors, and is endothelium‐independent. British Journal of Pharmacology (2004) 142, 435–442. doi:10.1038/sj.bjp.0705810

Journal

British Journal of Pharmacology – Wiley

Published: Jun 1, 2004

References

  • Mechanisms underlying tissue selectivity of anandamide and other vanilloid receptor agonists
    ANDERSSON, ANDERSSON; ADNER, ADNER; HOGESTATT, HOGESTATT; ZYGMUNT, ZYGMUNT
  • G protein‐coupled endothelial receptor for atypical cannabinoid ligands modulates a Ca 2+ ‐dependent K + current
    BEGG, BEGG; MO, MO; OFFERTALER, OFFERTALER; BATKAI, BATKAI; PACHER, PACHER; RAZDAN, RAZDAN; LOVINGER, LOVINGER; KUNOS, KUNOS
  • The endothelial component of cannabinoid‐induced relaxation in rabbit mesenteric artery depends on gap junctional communication
    CHAYTOR, CHAYTOR; MARTIN, MARTIN; EVANS, EVANS; RANDALL, RANDALL; GRIFFITH, GRIFFITH
  • Cannabinoid (CB 1 ) receptor expression is associated with mesenteric resistance vessels but not thoracic aorta in the rat
    DARKER, DARKER; MILLNS, MILLNS; SELBIE, SELBIE; RANDALL, RANDALL; S‐BAXTER, S‐BAXTER; KENDALL, KENDALL
  • The activity of anandamide at vanilloid VR1 receptors requires facilitated transport across the cell membrane and is limited by intracellular metabolism
    DE PETROCELLIS, DE PETROCELLIS; BISOGNO, BISOGNO; MACCARRONE, MACCARRONE; DAVIS, DAVIS; FINAZZI‐AGRO, FINAZZI‐AGRO; DI MARZO, DI MARZO
  • Production and physiological actions of anandamide in the vasculature of the rat kidney
    DEUTSCH, DEUTSCH; GOLIGORSKY, GOLIGORSKY; SCHMID, SCHMID; KREBSBACH, KREBSBACH; SCHMID, SCHMID; DAS, DAS; DEY, DEY; ARREAZA, ARREAZA; THORUP, THORUP; STEFANO, STEFANO; MOORE, MOORE
  • Evidence of a novel site mediating anandamide‐induced negative inotropic and coronary vasodilatator responses in rat isolated hearts
    FORD, FORD; HONAN, HONAN; WHITE, WHITE; HILEY, HILEY
  • Anandamide‐induced relaxation of sheep coronary arteries: the role of the vascular endothelium, arachidonic acid metabolites and potassium channels
    GRAINGER, GRAINGER; BOACHIE‐ANSAH, BOACHIE‐ANSAH
  • Characterisation of vasorelaxant responses to anandamide in the rat mesenteric arterial bed
    HARRIS, HARRIS; MCCULLOCH, MCCULLOCH; KENDALL, KENDALL; RANDALL, RANDALL
  • Endothelium‐independent relaxation to cannabinoids in rat‐isolated mesenteric artery and role of Ca 2+ influx
    HO, HO; HILEY, HILEY
  • Cannabinoid‐induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors
    JÁRAI, JÁRAI; WAGNER, WAGNER; VARGA, VARGA; LAKE, LAKE; COMPTON, COMPTON; MARTIN, MARTIN; ZIMMER, ZIMMER; BONNER, BONNER; BUCKLEY, BUCKLEY; MEZEY, MEZEY; RAZDAN, RAZDAN; ZIMMER, ZIMMER; KUNOS, KUNOS
  • Characterisation and modulation of EDHF‐mediated relaxations in the rat isolated superior mesenteric arterial bed
    MCCULLOCH, MCCULLOCH; BOTTRILL, BOTTRILL; RANDALL, RANDALL; HILEY, HILEY
  • Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats
    MULVANY, MULVANY; HALPERN, HALPERN
  • Anandamide‐induced vasorelaxation in rabbit aortic rings has two components: G protein dependent and independent
    MUKHOPADHYAY, MUKHOPADHYAY; CHAPNICK, CHAPNICK; HOWLETT, HOWLETT
  • Selective ligands and cellular effectors of a G protein‐coupled endothelial cannabinoid receptor
    OFFERTÁLER, OFFERTÁLER; MO, MO; BATKAI, BATKAI; LIU, LIU; BEGG, BEGG; RAZDAN, RAZDAN; MARTIN, MARTIN; BUKOSKI, BUKOSKI; KUNOS, KUNOS
  • Characterisation of the vasorelaxant properties of the novel endocannabinoid N–arachidonoyl–dopamine (NADA)
    O'SULLIVAN, O'SULLIVAN; KENDALL, KENDALL; RANDALL, RANDALL
  • Vanilloid receptors on capsaicin‐sensitive sensory nerves mediate relaxation to methanandamide in the rat isolated mesenteric arterial bed and small mesenteric arteries
    RALEVIC, RALEVIC; KENDALL, KENDALL; RANDALL, RANDALL; ZYGMUNT, ZYGMUNT; MOVAHED, MOVAHED; HÖGESTÄTT, HÖGESTÄTT
  • An endogenous cannabinoid as an endothelium‐derived vasorelaxant
    RANDALL, RANDALL; ALEXANDER, ALEXANDER; BENNETT, BENNETT; BOYD, BOYD; FRY, FRY; GARDINER, GARDINER; KEMP, KEMP; MCCULLOCH, MCCULLOCH; KENDALL, KENDALL
  • Differential effects of L‐arginine on the inhibition by N G ‐nitro‐L‐arginine methyl ester of basal and agonist‐stimulated EDRF activity
    RANDALL, RANDALL; GRIFFITH, GRIFFITH
  • Cardiovascular effects of cannabinoids
    RANDALL, RANDALL; HARRIS, HARRIS; KENDALL, KENDALL; RALEVIC, RALEVIC
  • Anandamide and endothelium‐derived hyperpolarizing factor act via a common vasorelaxant mechanism in rat mesentery
    RANDALL, RANDALL; KENDALL, KENDALL
  • Characterization and distribution of binding sites for (3H)‐SR 141716A, a selective brain (CB1) cannabinoid receptor antagonist, in rodent brain
    RINALDI‐CARMONA, RINALDI‐CARMONA; PIALOT, PIALOT; CONGY, CONGY; REDON, REDON; BARTH, BARTH; BACHY, BACHY; BRELIERE, BRELIERE; SOUBRIE, SOUBRIE; LE FUR, LE FUR
  • Mechanisms of vasorelaxation to testosterone in the rat aorta
    TEP‐AREENAN, TEP‐AREENAN; KENDALL, KENDALL; RANDALL, RANDALL
  • Regional differences in anandamide‐ and methanandamide‐induced membrane potential changes in rat mesenteric arteries
    VANHEEL, VANHEEL; VAN DE VOORDE, VAN DE VOORDE
  • Mesenteric vasodilation mediated by endothelial anandamide receptors
    WAGNER, WAGNER; VARGA, VARGA; JARAI, JARAI; KUNOS, KUNOS
  • A comparison of EDHF‐mediated and anandamide‐induced relaxations in the rat isolated mesenteric artery
    WHITE, WHITE; HILEY, HILEY
  • Mechanisms of anandamide‐induced vasorelaxation in rat isolated coronary arteries
    WHITE, WHITE; HO, HO; BOTTRILL, BOTTRILL; FORD, FORD; HILEY, HILEY
  • Studies on the effects of anandamide in rat hepatic artery
    ZYGMUNT, ZYGMUNT; HOGESTATT, HOGESTATT; WALDECK, WALDECK; EDWARDS, EDWARDS; KIRKUP, KIRKUP; WESTON, WESTON
  • Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide
    ZYGMUNT, ZYGMUNT; PETERSSON, PETERSSON; ANDERSSON, ANDERSSON; CHUANG, CHUANG; SORGARD, SORGARD; DI MARZO, DI MARZO; JULIUS, JULIUS; HOGESTATT, HOGESTATT

You’re reading a free preview. Subscribe to read the entire article.

Try 2 weeks free now

DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

or browse the journals available

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$499/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

Sign up
for free
Start 14 day
Free Trial