Modulation of autonomic responses in normal and denervated isolated canine atria by substance P

The experiments were performed to determine whether the neuromodulatory effect of substance P (SP) could be demonstrated in the isolated atrium. Strips from the right (RA) and left atria (LA) of normal (control) and denervated canine hearts were placed in an isolated muscle bath, and isometric muscle tension was measured. Inotropic responses to direct muscarinic stimulation were obtained with 1 x 10(-9) to 1 x 10(-8) M acetylcholine (ACh), and responses to stimulation of the intramyocardial intrinsic cardiac nerves (ICN) were produced with nicotine (Nic), 1.0-10 x 10(-6) M. The same drugs were tested in the presence of 1 x 10(-6) M SP, which had no significant inotropic effects of its own. Responses to ACh were unaffected by SP. The primary negative inotropic response to Nic was greatly attenuated by SP in both control and denervated atria, whereas the secondary positive response in control atria was unaffected. This inhibition was very pronounced in LA but less so in the RA. We conclude that SP appears to modulate the responses of the ICN to nicotinic stimulation in a manner similar to that previously observed in intact animals. This mechanism may provide a means of direct modification of efferent cardiac responses by afferent nerves within the heart itself.