Characterization of responses to neurokinin A in the isolated perfused guinea pig heart

Goals of this study were to identify and characterize effects of neurokinin A (NKA) in isolated guinea pig hearts. Bradycardia, augmentation of ventricular contractions, and reduction of perfusion pressure were prominent responses to bolus injections of NKA (0.25-25 nmol). NKA was more potent than substance P (SP) in causing bradycardia but did not differ in potency for lowering perfusion pressure. Doses of SP of 25 nmol or less decreased ventricular force, whereas 100 nmol caused a biphasic response. The percent decrease in heart rate produced by 25 nmol NKA was reduced from 58.0 +/- 4.8 to 39.6 +/- 3.5% in the presence of 1 mu M atropine (n = 5). The positive inotropic response to 25 nmol of NKA in spontaneously beating hearts was replaced by a negative inotropic response during pacing (22.5 +/- 3.3% increase vs. 11.7 +/- 1.7% decrease, n. = 5). Reserpine pretreatment did not affect the positive inotropic response to NKA. Specific binding sites for I-125-labeled NKA were localized to intracardiac ganglia and coronary arteries but not to myocardium. It was concluded that 1) negative chronotropic responses to NKA involve cholinergic and noncholinergic mechanisms, and 2) the positive inotropic response is an indirect action.