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: email@example.com or firstname.lastname@example.org )
AJP - Heart and Circulatory Physiology – The American Physiological Society
Published: Aug 1, 2005
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
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
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.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera