Abstract
We studied the effect of sensory nerve peptide substance P (SP) and neurokinin A (NKA) in isolated perfused guinea pig lungs. SP and NKA increased pulmonary arterial pressure, capillary pressure, pulmonary venous resistance, and lung weight, but they did not change pulmonary arterial resistance or pulmonary vascular permeability. The effects of SP on pulmonary vascular dynamics were greater than those of NKA. Ozagrel hydrochloride, a thromboxane synthase inhibitor, partially attenuated the effect of SP. This indicates that thromboxane contributes to SP-induced pulmonary vasoreactivity. However, ozagrel hydrochloride did not change the effects of NKA. FK224, an NK-1/NK-2 receptor antagonist, abolished both SP- and NKA-induced pulmonary vasoconstriction. This indicates that SP and NKA acted on the pulmonary vasculature through the NK-1 or NR-2 receptor, or both. Papaverine, a smooth muscle relaxant, abolished the effects of SP. The SP-induced increase in lung weight was caused by a rise in pulmonary hydrostatic pressure, especially that caused by pulmonary venoconstriction.
