Changes in ANP responsiveness of normal and hypertensive porcine intrapulmonary arteries during maturation

Pulmonary vascular resistance falls rapidly after birth, but endothelium-de pendent relaxation is relatively poor during the perinatal period. Atrial n atriuretic peptide (ANP) is a potent vasodilator; however, its role in the process of perinatal adaptation is uncertain. Porcine intrapulmonary condui t arteries (IPA) from fetal, newborn (<5 min), 3-, 6, and 17-d-old, and adu lt pigs, and from piglets made hypoxic from 0 to 3, 3 to 6, or 14 to 17 d, were isolated and mounted for isometric force recording. Rings were precont racted with prostaglandin-F-2 alpha (PGF(2 alpha), 10 mu M) or KCl (40 mM). ANP was added cumulatively (10 pM to 100 nM). C-type natriuretic peptide ( CNP) was added as a single concentration of 100 nM. Accumulation of cGMP un der basal conditions and stimulated by ANP or CNP was measured by radioimmu noassay system. Frozen sections of lung tissue were incubated with I-125-la beled alpha-ANP, and binding site density was assessed on IPA with an image analysis system. ANP relaxed IPA in pigs at all ages, but the effect was s ignificantly greater at 6 and 17 d of age. Hypoxia in animals from 14 to 17 d old impaired ANP-induced relaxation. CNP relaxed IPA poorly: <12% at all ages. ANP increased cGMP accumulation in both normal and hypo:tic animals. CNP did not increase cGMP generation in IPA fi om normal animals but did s o in IPA from 3-d-old hypoxic animals. ANP-specific binding sites were demo nstrated on the pulmonary artery smooth muscle cells, with greater binding in the young animals. The increased relaxant responses to ANP during adapta tion may be important in maintaining low pulmonary vascular resistance. In contrast, CNP was largely ineffective in relaxing pulmonary arteries.