TACHYKININ ANTAGONISTS IN CAROTID-BODY RESPONSES TO HYPOXIA AND SUBSTANCE-P IN THE RAT

In the present study, we tested the hypothesis that substance P (SP) i s an excitatory peptide to the rat carotid body and plays an important role in chemosensory excitation by hypoxia. Chemosensory discharge wa s recorded from the cut carotid sinus nerve in 19 anaesthetized, paral yzed and mechanically ventilated rats. Intracarotid administration of SP augmented the chemoreceptor activity in a dose-dependent manner. Ma ximal excitation was seen with 10 nmol SP. Carotid body stimulation by SP was independent of its effects on arterial blood pressure. The eff ect of SP antagonists, D-Pro(2)-D-Trp(7,9)-SP (DPDT-SP) or Spantide, o n chemoreceptor responses to SP and hypoxia was examined in 12 rats. C lose carotid body administration of either antagonist at doses of 40 m u g.kg(-1).min(-1) elicited an augmentation followed by a progressive depression of baseline carotid body activity. SP antagonists significa ntly reduced peptide-induced carotid body stimulation and also markedl y attenuated the chemoreceptor response to hypoxia. Systemic administr ation of sodium bicarbonate stimulated the carotid bodies, presumably by releasing CO2, and the bicarbonate-induced chemoreceptor stimulatio n was not affected by SP antagonists. From these results we conclude t hat in rats (a) SP stimulates the carotid bodies independently of its effects on arterial blood pressure, and (b) SP is associated with the chemosensory stimulation by hypoxia but not with other excitatory stim uli.