Introduction: Natriuretic peptides are the most potent stimulants of cGMP production by particulate guanylyl cyclase (pGC). Atrial natriuretic peptide (ANP) is of cardiac origin and acts at targets distant from its site of formation and release. C-type natriuretic peptide (CNP) is more widely distributed and has been recently localized to vascular endothelium. These peptides activate pGC by distinct A (ANP) and B (CNP) receptors. We studied the effect of ANP and CNP in the pulmonary vasculature of the developing lamb. Methods: Fifth generation pulmonary arteries (PA) and veins (PV) were isolated from late gestation fetal (n=5) and 4-6 week old juvenile (n=8) lambs, and studied using conventional tissue bath techniques. Rings were preconstricted with norepinephrine following pretreatment with LNA to block cGMP production by the NO-soluble guanylate cyclase pathway, as well as indomethacin and propranolol. Concentration response curves were then generated for ANP and CNP (0.1 to 100 nM). Some vessels were pretreated with the cGMP kinase inhibitor Rp-8Br-PET-cGMPS to demonstrate that relaxations were mediated by this kinase. Results: EC50 values for CNP and ANP are shown for both vessel types in the table (* p < 0.05 vs ANP. ** p < 0.05 vs PA, p<0.05 vs fetal). In addition, maximal relaxations to 100nM CNP were blunted in fetal vs juvenile PA (58±9% vs 80±6%, p<0.05). Conclusion: We conclude that CNP is a potent dilator of PV from both fetal and juvenile lambs, but is a less potent dilator of PA than ANP. PA from juvenile lambs are significantly more responsive to CNP than fetal PA, which indicates that postnatal changes in pulmonary blood flow may alter expression of the pGC-B receptor.

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