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

Learn More →

Hemodynamic profile, responsiveness to anandamide, and baroreflex sensitivity of mice lacking fatty acid amide hydrolase

Hemodynamic profile, responsiveness to anandamide, and baroreflex sensitivity of mice lacking... The endocannabinoid anandamide exerts neurobehavioral, cardiovascular, and immune-regulatory effects through cannabinoid receptors (CB). Fatty acid amide hydrolase (FAAH) is an enzyme responsible for the in vivo degradation of anandamide. Recent experimental studies have suggested that targeting the endocannabinergic system by FAAH inhibitors is a promising novel approach for the treatment of anxiety, inflammation, and hypertension. In this study, we compared the cardiac performance of FAAH knockout (FAAH –/– ) mice and their wild-type (FAAH +/+ ) littermates and analyzed the hemodynamic effects of anandamide using the Millar pressure-volume conductance catheter system. Baseline cardiovascular parameters, systolic and diastolic function at different preloads, and baroreflex sensitivity were similar in FAAH –/– and FAAH +/+ mice. FAAH –/– mice displayed increased sensitivity to anandamide-induced, CB 1 -mediated hypotension and decreased cardiac contractility compared with FAAH +/+ littermates. In contrast, the hypotensive potency of synthetic CB 1 agonist HU-210 and the level of expression of myocardial CB 1 were similar in the two strains. The myocardial levels of anandamide and oleoylethanolamide, but not 2-arachidonylglycerol, were increased in FAAH –/– mice compared with FAAH +/+ mice. These results indicate that mice lacking FAAH have a normal hemodynamic profile, and their increased responsiveness to anandamide-induced hypotension and cardiodepression is due to the decreased degradation of anandamide rather than an increase in target organ sensitivity to CB 1 agonists. contractility; hypertension; cannabinoids; endocannabinoids Address for reprint requests and other correspondence: P. Pacher or G. Kunos, National Institutes of Health, NIAAA, Laboratory of Physiological Studies, 5625 Fishers Lane MSC 9413, Rm. 2S24, Bethesda, MD 20892–9413 (e-mail: pacher@mail.nih.gov or gkunos@mail.nih.gov ) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Heart and Circulatory Physiology The American Physiological Society

Hemodynamic profile, responsiveness to anandamide, and baroreflex sensitivity of mice lacking fatty acid amide hydrolase

Loading next page...
 
/lp/the-american-physiological-society/hemodynamic-profile-responsiveness-to-anandamide-and-baroreflex-Mxdel3DRGn
Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0363-6135
eISSN
1522-1539
DOI
10.1152/ajpheart.00107.2005
pmid
15821037
Publisher site
See Article on Publisher Site

Abstract

The endocannabinoid anandamide exerts neurobehavioral, cardiovascular, and immune-regulatory effects through cannabinoid receptors (CB). Fatty acid amide hydrolase (FAAH) is an enzyme responsible for the in vivo degradation of anandamide. Recent experimental studies have suggested that targeting the endocannabinergic system by FAAH inhibitors is a promising novel approach for the treatment of anxiety, inflammation, and hypertension. In this study, we compared the cardiac performance of FAAH knockout (FAAH –/– ) mice and their wild-type (FAAH +/+ ) littermates and analyzed the hemodynamic effects of anandamide using the Millar pressure-volume conductance catheter system. Baseline cardiovascular parameters, systolic and diastolic function at different preloads, and baroreflex sensitivity were similar in FAAH –/– and FAAH +/+ mice. FAAH –/– mice displayed increased sensitivity to anandamide-induced, CB 1 -mediated hypotension and decreased cardiac contractility compared with FAAH +/+ littermates. In contrast, the hypotensive potency of synthetic CB 1 agonist HU-210 and the level of expression of myocardial CB 1 were similar in the two strains. The myocardial levels of anandamide and oleoylethanolamide, but not 2-arachidonylglycerol, were increased in FAAH –/– mice compared with FAAH +/+ mice. These results indicate that mice lacking FAAH have a normal hemodynamic profile, and their increased responsiveness to anandamide-induced hypotension and cardiodepression is due to the decreased degradation of anandamide rather than an increase in target organ sensitivity to CB 1 agonists. contractility; hypertension; cannabinoids; endocannabinoids Address for reprint requests and other correspondence: P. Pacher or G. Kunos, National Institutes of Health, NIAAA, Laboratory of Physiological Studies, 5625 Fishers Lane MSC 9413, Rm. 2S24, Bethesda, MD 20892–9413 (e-mail: pacher@mail.nih.gov or gkunos@mail.nih.gov )

Journal

AJP - Heart and Circulatory PhysiologyThe American Physiological Society

Published: Aug 1, 2005

There are no references for this article.

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


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

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