Presynaptic regulation of cardiac norepinephrine release in ischemia.
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 alpha2-adrenoceptors, beta2-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 alpha2-adrenoceptors lose their activity, whereas stimulatory beta2-adrenoceptors are sensitized. Inhibitory adenosine A1-receptors gain importance during ischemia owing to endogenous adenosine formation. Bradykinin- and angiotensin-mediated stimulation of norepinephrine release is not affected under ischemic conditions.
Grimm
M
M
Medical Clinic II, Medical University Lübeck, Germany.
Kurz
T
T
Schwarz
M
M
Richardt
D
D
Schäfer
U
U
Katus
H A
HA
Richardt
G
G
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D004558:Electric Stimulation; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D057911:Angiotensin Receptor Antagonists; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D009638:Norepinephrine