Analysis of carotid chemoreceptor responses to substance P analogue in anaesthetized cats

Analogues of Substance P (SP) have been shown to act as SP receptor antagonists in various physiological systems. We have previously shown that the carotid body sensory response to hypoxia could be attenuated by D-Pro2-D-Trp7,9-SP (DPDT-SP) and suggested that SP may be important for chemoreception. In the absence of detailed characterization of the antagonistic effects of DPDT-SP, the role of SP in carotid body chemoreception remains uncertain. The present study was undertaken to analyze the effects of DPDT-SP on carotid body activity in anaesthetized cats (n = 18). Intra-carotid infusion of DPDT-SP antagonized SP-induced chemoreceptor stimulation. 90% blockade of SP responses was obtained at infusion rates of 15 micrograms/kg per min of DPDT-SP for 15 min. By contrast, infusions of either saline (controls) or at doses below 10 micrograms/kg per min had no effect on SP responses. The doses that effectively antagonized SP excitation (i.e., 15 micrograms/kg per min) also blocked or markedly attenuated the chemoreceptor responses to hypoxia, without affecting the carotid body stimulation caused by nicotine. The effects of DPDT-SP were associated with significant reduction in baseline activity in normoxia. The antagonistic effects were reversible after terminating the infusion of DPDT-SP. Increasing the dose to 25 micrograms/kg per min, however, abolished the carotid body excitation by any of the stimuli tested (i.e., SP, hypoxia and nicotine), indicating that at higher doses DPDT-SP is non-selective. These results demonstrate that DPDT-SP given in adequate doses to block SP response also attenuates or abolishes the carotid body excitation by hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)