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 porcine pulmonary arteries and compared it with the adult by studying the bradykinin-, substance P- and acetylcholine-induced relaxations in different arteries.


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 and 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 mounted for isometric force recording, contracted first with K+ = 125 mmol/l (reference contraction). Cumulative concentration-response curves to acetylcholine, substance P or bradykinin were obtained from prostaglandin F2 alpha (30 mumol/l) precontracted vessels. The effects of captopril and O2(95 or 8%) were also determined. Experiments were terminated by adding 100 mumol/l papaverine, obtaining maximal relaxation, which was used for normalising relaxations.


RESULTS
(i) Acetylcholine: In resistance arteries, relaxations were absent in the newborn and the adult. In conduit arteries, they were present from 60-84 h onward. (ii) Substance P: In resistance arteries, relaxations were only present in the adult. In the other two types of arteries, rudimentary relaxations were present from the mature foetal stage onward. (iii) Bradykinin: In resistance arteries, identical relaxations were present at all ages which, in the foetus and the adult, were insensitive to changes in O2 levels (95 to 8%). In conduit arteries, concentration-dependent relaxations were present from birth, increasing in amplitude with age and these were potentiated by captopril. Foetal conduit arteries relaxed to the single application of 0.1 mumol/l bradykinin, indicating age-dependent tachyphylaxis.


CONCLUSIONS
(i) Bradykinin is unique among endothelium-dependent vasodilators in being able to relax all vascular segments, at all ages, subject to tachyphylaxis and bradykinin-breakdown but independent of the prevailing O2 concentration. (ii) Heterogeneity of the relaxations between conduit and resistance arteries is evident from the mature foetal stage onward. (iii) The type of agonist, the type of vessel and the age each independently determine the presence or absence of endothelial relaxations. Therefore, the perinatal pulmonary circulation is not immature with respect to endothelial-dependent relaxation; rather, the nature of this process changes within the perinatal period and between birth and adulthood.
Boels
P J
PJ
Vascular Biology and Pharmacology Unit, Institute of Child Health, London, UK. pboels@ich.ucl.ac.uk
Deutsch
J
J
Gao
B
B
Haworth
S G
SG
D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001920:Bradykinin / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D066298:In Vitro Techniques; D010100:Oxygen / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D013373:Substance P; D002216:Captopril; D000109:Acetylcholine; D010100:Oxygen; D001920:Bradykinin