Characterisation of the response of equine digital arteries and veins to substance P

Substance P (SP), a potent vasodilator, has been detected in equine digital sensory-motor nerves. The aim of the study was to characterise the functional responses of equine digital blood vessels to exogenous SP. Pre-constricted equine digital arteries (EDA) and veins (EDV) vasodilated in a biphasic, endothelium- and concentration-dependent manner to SP. A nitric oxide (NO) synthase inhibitor N-omega-nitro-L-arginine methyl ester hydrochloride (L-NAME; 300 muM) inhibited both phases of the relaxation response curve of EDAs to SP by >70%. In EDVs, the first relaxant phase to SP was largely L-NAME-resistant, whereas the second phase was inhibited by 60%. Both L- NAME and a cyclooxygenase inhibitor (ibuprofen; 10 muM) were required to inhibit EDV relaxation to SP by greater than or equal to80%. Experiments determining the receptor mediated responses to physiological concentrations of SP (1 nM) revealed that the relaxant responses of both EDA and EDV were inhibited by a neurokinin- 1 (NK1) receptor antagonist (CP-96 345; 10 nM). In conclusion, SP is an endothelium- dependent vasodilator of both EDA and EDV. NO is the predominant pathway activated in EDA, whereas both prostacyclin and NO pathways are involved in EDVs. NK1 receptors appear to mediate responses to low concentrations of SP.