7 Jun. 2007
ADMA - a new target for the treatment of opiode tolerance and addiction?
In the latest issue of Nitric oxide Dr. Anousheh Kielstein and coworkers
published an interesting paper on the possible role of ADMA for the modulation
of nociception in opiate tolerance and addiction. Aside from sepsis, opioide
tolerance and addiction might be one of the few disease where a temporary and
local increase in ADMA seems to be beneficial. It is well known that
increased NO production-either prior to or concurrently with opioid
administration-results in an enhanced rate and extent of development of
tolerance to morphine in mice. NO produces an alteration in the µ-opioid
receptor that increases constitutive receptor activity. It thereby reduces
the ability of a selective µ-opioid agonist to activate the µ-opioid receptor;
these in vitro molecular effects occur in a time course consistent with the in
vivo development of antinociceptive tolerance in mice. Selective blockade of
nNOS the synthetic NOS inhibitor 7-nitroindazole attenuates morphine withdrawal
in opiate dependent rats, suggesting nNOS as a viable target for development of
pharmacotherapies. Dr. Kielstein and her co-workers hypothesize that, by
inhibiting nNOS and reducing NO levels, ADMA may decrease µ-opioid receptor
constitutive activity, resulting in alteration of the analgesic dose-response
curve of morphine. http://dx.doi.org/10.1016/j.niox.2007.05.005
21 Dec. 2006
ADMA predicts survival in patients with coronary artery disease
In the latest online publication of Clinical Chemistry, Meinitzer et al.
present data on ADMA and mortality in the The Ludwigshafen Risk and
Cardiovascular Health Study. It is the biggest clinical study on ADMA as a
cardiovascular risk marker yet. An impressive number of 3297 patients were
included into the study. Based on coronary angiography 2543 patients with
coronary artery disease as well as 695 subjects without coronary artery
disease were identified. Subjects and patients were followed for a median
of 5.45 years. ADMA correlated with age, female gender, diabetes mellitus
and current smoking and CRP. Moreover, even after accounting for confounding
variables, ADMA in the highest quartile increased the risk of total and
cardiovascular mortality by 1.87 (95% CI 1.43-2.44).
http://www.clinchem.org/cgi/content/abstract/clinchem.2006.076828v1
25 Oct. 2006
New treatment for elevated ADMA levels !
A research team headed by Dr. Laura F. Michael from
Eli Lilly and company could show that the farnesoid X
receptor agonist GW4064 increased the expression of
dimethylarginine dimethylaminohydrolase-1(DDAH1)in the
liver of rats. DDAH is the main enzyme lowering ADMA
levels. The drug lead to a dose dependent increase in
DDAH 1 expression in the liver. The level of serum
ADMA was reduced concomitantly. Based on our knowledge
concerning the detrimental effects of ADMA in the
process of atherosclerosis, this drug might possibly
prevent atherosclerotic disease or slow down its
progression.
PDF
29 Jun. 2006
Stroke is a devastating disease that
affects about 750,000/year people in the United States, ranks as the third
leading cause of death, causes long-term disability and imposes an economic
burden on the health care system. In a recent study, published online on
June, 29 2006 in Stroke, it was shown that short term infusion of ADMA in
healthy subjects decreased cerebral blood flow. Furthermore, the arterial
stiffness, an important prognostic marker of cardiovascular events, also
increased in response to ADMA infusion. These results suggest that ADMA is an
important endogenous modulator of cerebral vascular tone and may be involved
in the pathogenesis of cerebrovascular disease.
PDF
14. Apr. 2006
Symmetrical Dimethylarginine: A New Combined Parameter
for Renal Function and Extent of Coronary Artery Disease
16. Nov. 2005
Arginine Metabolism, Pulmonary Hypertension and
Sickle Cell disease
02 Aug. 2005
Asymmetric Dimethylarginine: A Cardiovascular Risk Factor and a Uremic Toxin Coming of Age?
08 Jun. 2005
ADMA predicts progression of renal disease and death in patients with chronic kidney disease
28 Apr. 2005
ADMA in idiopathic pulmonary arterial hypertension (IPAH)