Angiotensin II induces vascular endocannabinoid release, which attenuates its vasoconstrictor effect via CB1 cannabinoid receptors

Mária Szekeres, G. Nádasy, Gábor Turu, Eszter Soltész-Katona, Z. Tóth, A. Balla, Kevin J. Catt, L. Hunyady

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

In the vascular system angiotensin II (Ang II) causes vasoconstriction via the activation of type 1 angiotensin receptors. Earlier reports have shown that in cellular expression systems diacylglycerol produced during type 1 angiotensin receptor signaling can be converted to 2-arachidonoylglycerol, an important endocannabinoid. Because activation of CB1 cannabinoid receptors (CB 1R) induces vasodilation and reduces blood pressure, we have tested the hypothesis that Ang IIinduced 2-arachidonoylglycerol release can modulate its vasoconstrictor action in vascular tissue. Rat and mouse skeletal muscle arterioles and mouse saphenous arteries were isolated, pressurized, and subjected to microangiometry. Vascular expression of CB1R was demonstrated using Western blot and RT-PCR. In accordance with the functional relevance of these receptors WIN55212, a CB1R agonist, caused vasodilation, which was absent in CB1R knock-out mice. Inhibition of CB1Rs using O2050, a neutral antagonist, enhanced the vasoconstrictor effect of Ang II in wild type but not in CB1R knock-out mice. Inverse agonists of CB1R (SR141716 and AM251) and inhibition of diacylglycerol lipase using tetrahydrolipstatin also augmented the Ang II-induced vasoconstriction, suggesting that endocannabinoid release modulates this process via CB1R activation. This effect was independent of nitric-oxide synthase activity and endothelial function. These data demonstrate that Ang II stimulates vascular endocannabinoid formation, which attenuates its vasoconstrictor effect, suggesting that endocannabinoid release from the vascular wall and CB1R activation reduces the vasoconstrictor and hypertensive effects of Ang II.

Original languageEnglish
Pages (from-to)31540-31550
Number of pages11
JournalJournal of Biological Chemistry
Volume287
Issue number37
DOIs
Publication statusPublished - Sep 7 2012

Fingerprint

Cannabinoid Receptor CB1
Endocannabinoids
Vasoconstrictor Agents
Angiotensin II
Blood Vessels
Chemical activation
Angiotensin Type 1 Receptor
rimonabant
Vasoconstriction
Knockout Mice
Vasodilation
Lipoprotein Lipase
Nitric Oxide Synthase Type III
Diglycerides
Blood pressure
Arterioles
Nitric Oxide Synthase
Muscle
Rats
Skeletal Muscle

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Angiotensin II induces vascular endocannabinoid release, which attenuates its vasoconstrictor effect via CB1 cannabinoid receptors. / Szekeres, Mária; Nádasy, G.; Turu, Gábor; Soltész-Katona, Eszter; Tóth, Z.; Balla, A.; Catt, Kevin J.; Hunyady, L.

In: Journal of Biological Chemistry, Vol. 287, No. 37, 07.09.2012, p. 31540-31550.

Research output: Contribution to journalArticle

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