Author:
National Institutes of Health (June 29, 2001)
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Date Posted: Thu, August 02 2001, 13:51:22 PDT
In reply to:
LONDON (Reuters)
's message, "Scientists Stub Out Cannabis As Wonder Drug" on Mon, July 30 2001, 7:52:48 PDT
NATIONAL INSTITUTES OF HEALTH
National Institute on
Alcohol Abuse and Alcoholism
EMBARGOED FOR RELEASE
Friday, June 29, 2001
5:00 p.m. EST NIAAA Press Contacts:
Ann Bradley (301) 443-0595
Amy Matush (301) 443-0469
Marijuana-Like Substances Linked to Cirrhosis Complications
Marijuana-like substances (endocannabinoids) intrinsic in animals and
humans act at specific receptors on the blood vessel wall to produce
vasodilation, the generalized blood vessel dilation seen in many patients
with advanced liver cirrhosis, according to an article by George Kunos,
M.D., Ph.D., and colleagues in the July 1 issue of Nature Medicine (Volume
7, Number 7; Endocannabinoids acting at vascular CB1 receptors mediate the
vasodilated state in advanced liver cirrhosis). Dr. Kunos, who serves as
Scientific Director, Division of Intramural Clinical and Biological
Research, NIAAA, performed some of the research under a National Heart,
Lung, and Blood Institute (NHLBI) grant while at his previous position on
the faculty of the Department of Medicine at Virginia Commonwealth
University.
In advanced cirrhosis, vasodilation lowers blood pressure and increases
blood flow to the liver and gut. Due to liver scarring, this increased blood
flow meets with resistance, resulting in elevated portal pressure (portal
hypertension) that can cause fluid to accumulate in the abdomen (a condition
known as ascites) and dilated blood vessels to rupture-both life-threatening
complications. Prevailing theory has held that an unknown endogenous
vasodilator contributes to the maintenance of portal hypertension and the
development of ascites.
In the series of experiments reported July 1, Dr. Kunos and his colleagues
demonstrate that the elusive mediator is most likely an endocannabinoid
acting at vascular CB1 receptors. "Our findings raise the promising
possibility that CB1 receptor-blocking drugs can reverse the vasodilated
state and reduce the risk of death in patients who are awaiting liver
transplants," Dr. Kunos said.
The research team led by Dr. Kunos found elevated levels of the
endocannabinoid anandamide and low blood pressure in two distinct animal
models of cirrhosis. Using the CB1 antagonist SR141716A, they succeeded in
raising blood pressure and reducing portal pressure and blood flow to the
liver.
A separate experiment demonstrated that macrophages, a special type of
white blood cell isolated from the blood of cirrhotic humans and rats,
contained elevated levels of the endocannabinoid anandamide. When the
researchers injected such macrophages into healthy animals, they decreased
blood pressure-an effect that they also found could be prevented by
pretreatment with SR141719A.
In addition to elevated levels of anandamide, the researchers found
elevated cellular levels of its receptor; in human cirrhotic liver samples,
they identified a threefold increase in CB1 receptors in cells lining the
blood vessel walls. "Taken together, these findings strongly implicate
anandamide and vascular CB1 receptors in the vasodilated state in advanced
cirrhosis and indicate a novel approach for its management," the authors
conclude.
An estimated three and a half million Americans have liver cirrhosis - a
progressive disease that develops as a long-term consequence of chronic
alcoholism or viral hepatitis and produces scarring and eventual loss of
liver function. Cirrhosis is second only to traffic crashes as the leading
cause of alcohol-related deaths. At present, the only definitive treatment
is transplantation.
"New understandings of the mechanisms of cirrhosis recently have emerged,
providing hope that soon we may have medications that can interrupt or
reverse the disease process," said NIAAA Director Enoch Gordis, M.D. "The
work by Dr. Kunos and his colleagues extends that hope even to treatments
for end-stage cirrhosis."
For interviews with Dr. Kunos, please telephone 34-91-896-7000 June 28 and
29; after July 1, telephone his office (301/443-2069). For interviews with
Dr. Gordis, please telephone the NIAAA press office.
The National Institute on Alcohol Abuse and Alcoholism, a component of the
National Institutes of Health, U.S. Department of Health and Human Services,
conducts and supports approximately 90 percent of U.S. research on the
causes, consequences, prevention and treatment of alcohol abuse, alcoholism,
and alcohol problems and disseminates research findings to science,
practitioner, policy making, and general audiences.
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