Maturation of the response to bradykinin in resistance and conduit pulmonary arteries

Objective: Immaturity of the endothelial-dependent relaxation is thought to be characteristic of the newborn pulmonary elastic arteries. In adulthood, the reactivity of different pulmonary arterial segments varies. Therefore, we investigated the presence of endothelial heterogeneity in perinatal por cine pulmonary arteries and compared it with the adult by studying the brad ykinin-, substance P- and acetylcholine-induced relaxations in different ar teries. Methods: Three types of pulmonary arteries (large conduit elastic, distal branching and resistance-sized; in situ diameters 0.7-1.7, 0.3-0.5 a nd 0.1-0.2 mm, respectively) were isolated from lungs of adult (nine months ), young (60-84 h), newborn (4 min) and near-term foetal pigs. They were mo unted for isometric force recording, contracted first with K+=125 mmol/l (r eference contraction). Cumulative concentration-response curves to acetylch oline, substance P or bradykinin were obtained from prostaglandin F-2 alpha (30 mu mol/l) precontracted vessels. The effects of captopril and O-2(95 o r 8%) were also determined. Experiments were terminated by adding 100 (mu m ol/l papaverine, obtaining maximal relaxation, which was used for normalisi ng relaxations. Results: (i) Acetylcholine: In resistance arteries, relaxat ions were absent in the newborn and the adult. In conduit arteries, they we re present from 60-84 h onward. (ii) Substance P: In resistance arteries, r elaxations were only present in the adult. Tn the other two types of arteri es, rudimentary relaxations were present from the mature foetal stage onwar d. (iii) Bradykinin: In resistance arteries, identical relaxations were pre sent at all ages which, in the foetus and the adult, were insensitive to ch anges in O-2 levels (95 to 8%). In conduit arteries, concentration-dependen t relaxations were present from birth, increasing in amplitude with age and these were potentiated by captopril. Foetal conduit arteries relaxed to th e single application of 0.1 mu mol/l bradykinin, indicating age-dependent t achyphylaxis. Conclusions: (i) Bradykinin is unique among endothelium-depen dent vasodilators in bring able to relax all vascular segments, at all ages , subject to tachyphylaxis and bradykinin-breakdown but independent of the prevailing O-2 concentration. (ii) Heterogeneity of the relaxations between conduit and resistance arteries is evident from the mature foetal stage on ward. (iii) The type of agonist, the type of vessel and the age each indepe ndently determine the presence or absence of endothelial relaxations. There fore, the perinatal pulmonary circulation is not immature with respect to e ndothelial-dependent relaxation; rather, the nature of this process changes within the perinatal period and between birth and adulthood. (C) 1999 Publ ished by Elsevier Science B.V. All rights reserved.