Decreased vascular permeability response to substance P in airways of genetically hypertensive rats

1 The inbred genetically hypertensive strain (GH) of the Otago Wistar rat p ossesses more sensory neurons containing the neuropeptide substance P (SP) than does its genetically related control normotensive strain. 2 As SP contributes to airway inflammation by increasing microvascular perm eability, we assessed the extravasation of Evans Blue dye in trachea and ma in bronchus of anaesthetized GH and control rats, in the presence of endoge nous (capsaicin-liberated) or exogenous SP. 3 Following intravenous administration of either capsaicin (75 mu g kg(-1)) or SP (3.3 nmol kg(-1)), extravasation of Evans Blue in airways from GH ra ts was only about 60% of that in airways of control rats. This difference w as not gender-specific and responses to capsaicin were abolished by pretrea tment with a selective NK1 receptor antagonist SR 140333 (360 nmol kg(-1)). 4 By contrast, the extravasation of dye caused by intravenous 5-hydroxytryp tamine (0.5 mu mol kg(-1)) was similar in magnitude in both GH and control strains. 5 Falls in systemic arterial blood pressure in response to exogenous SP (0. 1-3 nmol kg(-1)) or acetylcholine (0.2-2 nmol kg(-1)) were also very simila r between strains, but those in response to capsaicin (75 mu g kg(-1)) in t he GH rats were about double those in control rats. The hypotensive respons e to SP was abolished by SR 140333, but that to capsaicin was unaffected. 6 Our results indicate that the increased peripheral innervation density by SP nerves in GH rats is accompanied by reduced inflammatory responses to S P. This does not involve decreased vasodilator potency of SP and is therefo re probably related to altered endothelial responsiveness.