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

Abstract

Aims The present study examined whether substance P (SP)-induced endothelium-dependent TXA 2-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 methods The 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 findings SP-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 NK 2 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 NK 2 receptors and TXA 2 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 TXA 2 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 NK 1 receptors and NO and TXA 2 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. Significance These regional differences in responses to SP may play important roles in maintaining the homogenous distribution of blood flow in the lung.