Persistent Ductus Arteriosus in the Brown-Norway Inbred Rat Strain

Persistent ductus arteriosus (PDA) is a common cardiovascular anomaly in children caused by the pathologic persistence of the left sixth pharyngeal arch artery. The inbred Brown-Norway (BN) rat presents with increased vascular fragility due to an aortic elastin deficit resulting from decreased elastin synthesis. The strikingly high prevalence of PDA in BN rats in a pilot study led us to investigate this vascular anomaly in 12 adolescent BN rats. In all BN rats, a PDA was observed macroscopically, whereas a ligamentum arteriosum was found in adult controls. The macroscopic appearance of the PDA was tubular (n = 2), stenotic (n = 8), or diverticular (n = 2). The PDA had the structure of a muscular artery with intimal thickening. In the normal closing ductus of the neonatal controls, the media consisted of layers of smooth muscle cells (SMCs) intermingled with layers of elastin. The intima was thin and poor in elastin. By contrast, the media of PDA in BN rats elastin lamellae were absent and the intima contained many elastic fibers. The abnormal distribution of elastin in the PDA of BN rats suggests that impaired elastin metabolism is related to the persistence of the ductus and implicates a genetically determined factor that may link the PDA with aortic fragility.