Action of substance P on the working rat heart.

The effect of substance P (SP) on the cardiodynamics of the isolated working rat heart perparation was examined. The peptide over the concentration range of 10(-8) to 10(-6) M was found to have no influence on aortic pressure, cardiac output, or cardiac work. However, a 10-15% reduction in coronary flow was observed at 1 x 10(-6) M substance P. Octapeptide substance P (SP4-11) exhibited a similar vasoconstrictive action. The IC50 of SP4-11 was 2 x 10(-13) M compared to an IC50 of 3.5 x 10(-8) M for substance P. Perfusion of the heart in the presence of bacitracin (1 x 10(-4) M), a protease inhibitor, prevented the reduction in coronary flow observed in the presence of substance P. By contrast, the reduction in coronary flow produced by octapeptide substance P was not altered by the presence of bacitracin. Thus, it appears that a C-terminal fragment such as SP4-11 may be responsible for the observed decrease in coronary flow.