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

Abstract

1 The inbred genetically hypertensive strain (GH) of the Otago Wistar rat possesses more sensory neurons containing the neuropeptide substance P (SP) than does its genetically related control normotensive strain. 2 As SP contributes to airway in¯ammation by increasing microvascular permeability, we assessed the extravasation of Evans Blue dye in trachea and main bronchus of anaesthetized GH and control rats, in the presence of endogenous (capsaicin-liberated) or exogenous SP. 3 Following intravenous administration of either capsaicin (75 mg kg 71 ) or SP (3.3 nmol kg 71 ), extravasation of Evans Blue in airways from GH rats was only about 60% of that in airways of control rats. This di erence was not gender-speci®c and responses to capsaicin were abolished by pretreatment with a selective NK 1 receptor antagonist SR 140333 (360 nmol kg 71 ). 4 By contrast, the extravasation of dye caused by intravenous 5-hydroxytryptamine (0.5 mmol kg 71 ) 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 71 ) or acetylcholine (0.2 ± 2 nmol kg 71 ) were also very similar between strains, but those in response to capsaicin (75 mg kg 71 ) in the GH rats were about double those in control rats. The hypotensive response to SP was abolished by SR 140333, but that to capsaicin was una ected. 6 Our results indicate that the increased peripheral innervation density by SP nerves in GH rats is accompanied by reduced in¯ammatory responses to SP. This does not involve decreased vasodilator potency of SP and is therefore probably related to altered endothelial responsiveness.