Endothelium-dependent relaxations of piglet pulmonary arteries augment with maturation.
To determine whether maturation alters endothelium-dependent responses in porcine pulmonary arteries, rings, with and without endothelium, of small pulmonary arteries taken from piglets of 3, 10, and 30 d of age were suspended in organ chambers filled with buffered salt solution, bubbled with 95% O2-5% CO2, and maintained at 37 degrees C. These studies were performed in the presence of indomethacin (10(-5) M) to inhibit prostaglandin synthesis. In rings without endothelium, potassium chloride (10(-2) to 8.5 x 10(-2) M) and histamine (10(-9) to 10(-5) M) caused concentration-dependent contractions. When normalized to maximal contractions achieved to each agonist, the concentration-effect curves to potassium chloride and histamine in rings without endothelium were similar at each age. Rings with endothelium showed a progressive shift to the right of the concentration-effect curve to histamine, possibly secondary to an increase in the basal release of, or responsiveness to, the endothelium-derived relaxing factor with maturation. Relaxations to sodium nitroprusside (10(-9) to 10(-5) M) were unaffected by age. In precontracted rings, acetylcholine (10(-9) to 10(-6) M), bradykinin (10(-10) to 10(-6) M), and the calcium ionophore A23187 (10(-9) to 10(-6) M) caused relaxations in rings with endothelium, but not in those without endothelium, which were greater at 10 and 30 d compared to 3 d; further augmentation at 30 d compared to 10 d was not observed. In rings without endothelium, changes in the responsiveness to nitric oxide (10(-9) to 10(-5) M), one of the proposed endothelium-derived relaxing factors, with age were comparable to those observed with endothelium-dependent relaxing agents. These studies demonstrate that endothelium-dependent relaxations increase with age, possibly due to changes in sensitivity of the smooth muscle to the endothelium-derived relaxing factor.
Zellers
T M
TM
Department of Pediatrics, Mayo Clinic, Rochester, Minnesota 55905.
Vanhoutte
P M
PM
D000818:Animals; D000831:Animals, Newborn; D005260:Female; D006632:Histamine / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000254:growth & development* / Q000648:ultrastructure; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects
D009599:Nitroprusside; D009569:Nitric Oxide; D011189:Potassium Chloride; D006632:Histamine