TY - JOUR
T1 - Presynaptic regulation of cardiac norepinephrine release in ischemia
AU - Grimm, Michael
AU - Kurz, Thomas
AU - Schwarz, Michael
AU - Richardt, Doreen
AU - Schäfer, Ulrich
AU - Katus, Hugo A.
AU - Richardt, Gert
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - In myocardial ischemia presynaptic regulation of norepinephrine release may be altered either by ischemic effects on presynaptic receptor signaling or by ischemia-evoked accumulation of endogenous agonists. Because presynaptic receptors are targets of several drugs, such alterations may have pharmacotherapeutic implications. We investigated the effect of brief ischemic periods on presynaptic regulation of norepinephrine release by α2-adrenoceptors, β1-adrenoceptors, adenosine A1-, angiotensin AT1-, and bradykinin B2-receptors in isolated perfused rat hearts. Exocytotic norepinephrine release was evoked by electrical field stimulation. Paired stimulations were performed to compare the pharmacologic intervention (S2) with the release under baseline conditions (S1), and the effects of receptor agonists and antagonists were compared under nonischemic and stop-flow conditions. In summary, during brief myocardial ischemia, presynaptic modulation of norepinephrine release is differentially regulated. Autoinhibitory α2-adrenoceptors lose their activity, whereas stimulatory β2-adrenoceptors are sensitized. Inhibitory adenosine A1-receptors gain importance during ischemia owing to endogenous adenosine formation. Bradykinin- and angiotensinmediated stimulation of norepinephrine release is not affected under ischemic conditions.
AB - In myocardial ischemia presynaptic regulation of norepinephrine release may be altered either by ischemic effects on presynaptic receptor signaling or by ischemia-evoked accumulation of endogenous agonists. Because presynaptic receptors are targets of several drugs, such alterations may have pharmacotherapeutic implications. We investigated the effect of brief ischemic periods on presynaptic regulation of norepinephrine release by α2-adrenoceptors, β1-adrenoceptors, adenosine A1-, angiotensin AT1-, and bradykinin B2-receptors in isolated perfused rat hearts. Exocytotic norepinephrine release was evoked by electrical field stimulation. Paired stimulations were performed to compare the pharmacologic intervention (S2) with the release under baseline conditions (S1), and the effects of receptor agonists and antagonists were compared under nonischemic and stop-flow conditions. In summary, during brief myocardial ischemia, presynaptic modulation of norepinephrine release is differentially regulated. Autoinhibitory α2-adrenoceptors lose their activity, whereas stimulatory β2-adrenoceptors are sensitized. Inhibitory adenosine A1-receptors gain importance during ischemia owing to endogenous adenosine formation. Bradykinin- and angiotensinmediated stimulation of norepinephrine release is not affected under ischemic conditions.
UR - http://www.scopus.com/inward/record.url?scp=0034932970&partnerID=8YFLogxK
U2 - 10.1097/00005344-200107000-00007
DO - 10.1097/00005344-200107000-00007
M3 - Journal articles
C2 - 11444503
AN - SCOPUS:0034932970
SN - 0160-2446
VL - 38
SP - 58
EP - 68
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 1
ER -