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) synth ase inhibition with NG-nitro-L-arginine (L-NOARG) did not unmask any inotro pic effect of adrenomedullin. The positive inotropic effect of isoprenaline (0.01 nM to 10 ELM) was identical after adrenomedullin, after L-NOARG, and after L-NOARG plus adrenomedullin (n = 6 each). In field-stimulated rat ve ntricular myocytes, adrenomedullin (1, 10, and 100 nM; n = 4 each) had impa ct neither on cell shortening nor on Ca2+ 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 concl usion, adrenomedullin is a potent coronary vasodilator, but has no signific ant effects on myocardial contractility in the rat. (C) 2000 Elsevier Scien ce B.V. All rights reserved.