Tadalafil gehört zur Gruppe der PDE5-Hemmer und wirkt über eine hochselektive Blockade des Enzyms Phosphodiesterase Typ 5. Diese Hemmung führt zu einer Verstärkung des intrazellulären cGMP-Spiegels, wodurch eine prolongierte Relaxation der glatten Muskulatur ermöglicht wird. Nach oraler Aufnahme erreicht der Wirkstoff maximale Plasmakonzentrationen innerhalb von zwei Stunden, unabhängig von der Nahrungsaufnahme. Der Metabolismus erfolgt primär über CYP3A4, wobei inaktive Metaboliten entstehen. Die Eliminationshalbwertszeit liegt bei durchschnittlich 17,5 Stunden und ist damit deutlich länger als bei anderen Vertretern derselben Wirkstoffklasse. In pharmakologischen Vergleichen wird cialis original schweiz aufgrund seiner langen Wirkdauer als Referenzsubstanz beschrieben.
Nanoparticle-mediated delivery of irbesartan reduces myocardial ischemia/reperfusion injury in mice via pparγ -dependent mechanisms
Nanoparticle-Mediated Delivery of Irbesartan Reduces Myocardial
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Yasuhiro Nakano, Tetsuya Matoba, Gentaro Ikeda, Kaku Nakano, Kensuke Egashira
Irbesartan-NP reduced infarct size via PPAR pathway.
Therapeutic effect of early myocardial reperfusion in
acute myocardial infarction is limited by ischemia-reperfusion
(IR) injury [1]. Novel drug delivery system might overcome
insufficient therapeutic efficacy of current medicines for IR
injury [2]. Here we hypothesized that nanoparticle-mediated
delivery of irbesartan, an angiotensin receptor blocker that
possesses a partial agonistic effect on peroxisome
reperfusion ameliorates IR injury [3]- [5].
In a murine model of a 30-min myocardial IR injury, we
examined cellular distribution of poly-lactic-co-glycolic acid
(PLGA) nanoparticle containing fluorescein isothiocyanate
(FITC-NP) or FITC solution intravenously administered 5
Figure 2. The role of AT1 receptor in infarct size after I/R.
mins before reperfusion. Significant FITC fluorescence was detected in IR myocardium after the treatment with FITC-NP
but not FITC solution. Flow cytometry (FCM) revealed
FITC-NP uptake by monocytes and neutrophils that were
recruited into the IR heart. Intravenous treatment with
irbesartan-containing nanoparticle (Irb-NP, 3.0 mg/kg
irbesartan) reduced infarct size 24 hours after reperfusion,
which was caQFHOHG E\ WKH SUHWUHDWPHQW ZLWK 33$5
antagonist GW9662 (Fig 1). Importantly, Irb-NP was
effective to reduce IR injury even in AT1-deficient mice. In
losartan-containing nanoparticle (10 mg/kg
losartan), or irbesartan solution (3.0 mg/kg) was ineffective
(Fig 2). Irb-13 VLJQLILFDQWO\ LQFUHDVHG 33$5 DFWLYLW\ DQG
decreased NF-%DFWLYLW\LQWKHQXFOHDUH[WUDFWIURP WKH ,5
myocardial tissue, which were canceled by the pretreatment
with GW9662. FCM 12 hours after reperfusion revealed that Irb-NP reduced neutrophils and Ly6Chigh inflammatory
[1] Derek M. Yellon, Derek J. Hausenloy. Myocardial Reperfusion Injury.
N Engl J Med. 2007;357:1121-1136.
[2] Abhiram Prasad, Gregg W. Stone, David R. Holmes, Bernard Gersh.
NP-mediated delivery of irbesartan into leukocytes and IR
Reperfusion Injury, Microvascular Dysfunction, and Cardioprotection.
myocardium reduced myocardial IR injury via
[3] Florian Leuschner, Filip K. Swirski, Ralph Weissleder, Matthias
Nahrendorf. Angiotensin-Converting Enzyme Inhibition Prevents the
Release of Monocytes From Their Splenic Reservoir in Mice With
Myocardial Infarction. Circulation Research. 2010;107:1364-1373
[4] Tian-li Yue, Robin E. Buckingham and Eliot H. Ohlstein. In Vivo
Myocardial Protection From Ischemia/Repefsuion Injury by the
Peroxisome Proliferator-Activated Receptor- Agonist Rosiglitazone.
All authors are with the Department of Cardiovascular medicine Kyushu
University Graduate School of Medical Sciences, 3-1-1 Maidashi,
[5] Leuschner F, Dutta P, Gorbatov R, et al. Therapeutic siRNA silencing
Higashi-ku, Fukuoka, Japan (corresponding author to provide phone:
(+81)92-642-5359; fax: (+81)92-642-5374; e-mail: