Regional heterogeneity of substance P-induced endothelium-dependent contraction, relaxation, and -independent contraction in rabbit pulmonary arteries

AimsThe present study examined whether substance P (SP)-induced endothelium-dependent TXA2-mediated contraction (EDC), nitric oxide (NO)-mediated relaxation (EDR), and endothelium-independent contraction (EIC) are different between the rabbit proximal and distal intrapulmonary arteries.Main methodsThe helically cut strips of isolated proximal and distal arteries were fixed vertically between hooks in organ bath, and changes in isometric tension were measured.Key findingsSP-induced EDC was greater in the distal than proximal arteries, and EDR was greater in the proximal than distal arteries. However, under the complete blockade of NK2 receptors and NO production, SP (10− 9–3 × 10− 7 M)-induced EDC did not differ between proximal and distal arteries. Under the complete blockade of NK2 receptors and TXA2 production, SP (3 × 10− 10–3 × 10− 8 M)-induced EDR was greater in the proximal than distal arteries. Neither contraction induced by U-46619, a TXA2 agonist, nor relaxation by sodium nitroprusside, an NO donor, was different between both portions of the arteries. Both ionomycin (10− 8 M)- and l-arginine (1 mM)-induced EDRs were also significantly greater in the proximal than distal arteries. Under the blockade of NK1 receptors and NO and TXA2 production, SP (10− 7 M)-induced EIC was greater in the distal than proximal arteries. In summary, the capacity for NO production is higher in the proximal than distal arteries, resulting in SP-induced higher EDR and lower EDC in the proximal arteries.SignificanceThese regional differences in responses to SP may play important roles in maintaining the homogenous distribution of blood flow in the lung.