This study aims to determine whether a relation exists between ischemia/reperfusion and myocardial B-type natriuretic peptide (BNP) mRNA expression independent of variations in intracavitary diastolic volume and consequently, of cardiomyocyte stretching. Twenty-three rats were subjected to the following conditions: control (C), 15 min of ischemia (I15), or ischemia plus 15 (R15), 30 (R30), or 45 (R45) min of reperfusion in the in situ hearts. Isolated hearts of sixteen additional rats (sham, n = 8; occlusion, n = 8) were perfused for studies in the absence of ventricular distension. All hearts were divided in two segments (ischemic and nonischemic). Ventricular distension was avoided by excluding the atria and mitral valves. In both experiments, BNP mRNA was quantified by real-time polymerase chain reaction in both nonischemic and ischemic regions. In the in situ hearts, myocardial BNP mRNA values at R15 (4.24 +/- 0.75) in the ischemic region were higher than in other groups (C: 1.43 +/- 0.81, P = 0.044; I15: 3.05 +/- 0.62, P = 0.048; R30: 0.76 +/- 0.84, P = 0.001; R45: 1.47 +/- 0.60, P = 0.046, [analysis of variance]). In isolated hearts without ventricular distension, myocardial BNP mRNA (arbitrary units) content at R15 in ischemic regions (4.54 +/- 0.26) was greater than in nonischemic regions in both occlusion (3.51 +/- 0.20, P < 0.001) and sham (3.38 +/- 0.25, P = 0.0001 and 3.47 +/- 0.19, P = 0.0001) groups. The present data show that ischemia/reperfusion is responsible for increased BNP mRNA myocardial content independent of changes of ventricular cavity diastolic volume.