Five indices were used to assess the degree of the ameliorative effects of adrenomedullin (Adm) in isoproterenol (ISO) induced injury of cardiac sarcoplasmic reticulum (SR) of rats: +/- LV dp/dtmax, SR Ca2+ uptake, Ca2+ release (in nmol/mg SR protein) and Ca(2+)-ATPase activity. Adm (5 x 10(-5) mol/L) was perfused into rat heart before cardiac function +/- LV dp/dtmax was determined. Cardiac SR was purified and SR Ca2+ uptake, Ca2+ release, Ca(2+)-ATPase activity, and 3H-ryanodine maximal binding (Bmax) were measured. After perfusion of Adm (5 x 10(-5) mol/L), the +LV dp/dtmax and -LV dp/dtmax in ISO injured heart were increased by 16.9% (2,135 +/- 281 vs 1980 +/- 302, P < 0.05) and 29.2% (1375 +/- 267 vs 1064 +/- 355, P < 0.05), respectively. Cardiac SR Ca2+ uptake and Ca2+ release were increased by 23.0% (15.0 +/- 1.4 vs 12.2 +/- 1.2, P < 0.01) and 43.5% (6.6 +/- 1.0 vs 4.6 +/- 0.6, P < 0.01), respectively. Ca(2+)-ATPase activity and 3H-ryanodine binding were increased by 23.0% (P < 0.01) and 42.2% (P < 0.05), respectively. It seems that Adm exerted a protective effect on cardiac function in injured rat heart by enhancing SR Ca2+ uptake and release, suggesting that Adm may play a therapeutic role in myocardial injury.