Adrenomedullin and myocardial contractility in the rat.
The effects of adrenomedullin in the regulation of myocardial contractility were investigated in the rat. In papillary muscles (n=6), adrenomedullin (0.1 to 10 nM) failed to show contractile effects. NO (nitric oxide) synthase inhibition with N(G)-nitro-L-arginine (L-NOARG) did not unmask any inotropic effect of adrenomedullin. The positive inotropic effect of isoprenaline (0. 01 nM to 10 microM) was identical after adrenomedullin, after L-NOARG, and after L-NOARG plus adrenomedullin (n=6 each). In field-stimulated rat ventricular myocytes, adrenomedullin (1, 10, and 100 nM; n=4 each) had impact neither on cell shortening nor on Ca(2+) transients. In isolated constant-flow perfused hearts (7.3+/-0.3 ml/min), adrenomedullin (1 nM, n=9; 10 nM, n=7) induced significant coronary vasodilation (-28%, -50%). In conclusion, adrenomedullin is a potent coronary vasodilator, but has no significant effects on myocardial contractility in the rat.
Stangl
V
V
Medizinische Klinik, Kardiologie, Angiologie, Pneumologie, Charité, Campus Mitte, Humboldt-Universität zu Berlin, Schumannstr. 20-21, D-10098 Berlin, Germany.
Dschietzig
T
T
Bramlage
P
P
Boyé
P
P
Kinkel
H T
HT
Staudt
A
A
Baumann
G
G
Felix
S B
SB
Stangl
K
K
D053607:Adrenomedullin; D000814:Aniline Compounds; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D019332:Endothelin-1 / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014966:Xanthenes
D000814:Aniline Compounds; D002316:Cardiotonic Agents; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D010455:Peptides; D014966:Xanthenes; D053607:Adrenomedullin; D019335:Nitroarginine; C059715:Fluo-3; D002118:Calcium