Effects of NK1 receptor antagonists on vasodilation induced by chemical and electrical activation of sensory C-fibre afferents in different organs.

The effects of the non-peptide NK1 receptor antagonists, CP 96,345 and RP-67,580, were investigated in a model using anaesthetized pigs. Both the blood flow in the internal maxillary and the bronchial artery (ultrasonic flowmetry) and the superficial blood flow in nasal mucosa and the skin (laser-Doppler flowmetry) were monitored simultaneously. Vasodilation induced by substance P administered i.v. systemically was blocked by pretreatment with CP-96,345, 3 mg kg-1 but not by RP-67,580. CP-96,345 had no effects on the vasodilation induced by calcitonin gene-related peptide or vasoactive intestinal polypeptide. The capsaicin-induced vasodilation in the superficial blood flow of the nasal mucosa and the skin, was reduced after the CP-96,345 pretreatment. The vasodilation induced by capsaicin infusion in the internal maxillary or the bronchial artery was not affected by the CP-96,345 pretreatment. Electrical stimulation of the vagal nerve induced a vasodilation in the bronchial circulation which was not attenuated by pretreatment with CP-96,345. In the nasal mucosa and the skin NK1 receptors seem to be involved in the vasodilation in the superficial small vessels, due to chemical activation of sensory C-fibre afferents. Furthermore, CP-96,345 is a useful tool in the evaluation of NK1 receptor-mediated responses. RP-67,580 which has been shown to have NK1 antagonistic properties in the rat has no such effects in the domestic pig.