Endothelium-Derived Relaxing Factor: Presence in Pulmonary and Systemic Arteries of the Newborn Guinea Pig

Abstract

ABSTRACT. Endothelium-derived relaxing factor (EDRF), believed to be nitric oxide or a compound that releases nitric oxide, is a potent vasodilator produced by some arteries in response to acetylcholine (ACh) and bradykinin (BK). ACh and BK are potent dilators of perinatal pulmonary and systemic arteries. The objectives of this study were to determine if EDRF is present in newborn vessels and if EDRF mediates the vasodilator actions of ACh and BK. Arterial rings from newborn guinea pigs, 1 to 3 d old, were obtained from a branch of the main pulmonary artery and the descending aorta for isometric force bioassays. At their optimal resting tension, the rings were preconstricted with phenylephrine lo-' M in KrebsHenseleit solution before adding incremental doses of ACh or BK. If the endothelium was intact, ACh (lo-' M) relaxed pulmonary arteries and aortas (64 f 7%, 72 f 9% relaxation, respectively, mean f SE). ACh-induced relaxation (ACh lo-' M) in the pulmonary artery and aorta, respectively, was significantly (p < 0.05) attenuated by 1 ) endothelial removal (11 f 9%, 28 f 10%) by rubbing the ring lumen; 2) methylene blue, 10" M, (6 f 8%, 7 f 3%) that inhibits EDRF-associated cGMP production in smooth muscle; and 3) methemoglobin, lo-' M, (13 f 9%, 17 f 7%) that binds EDRF. The results for BK were similar to ACh for the pulmonary artery but BK did not relax the aorta. Indomethacin diminished relaxation of the pulmonary artery and aorta to the submaximal dose (lo-' M) of ACh but indomethacin did not effect the relaxation to ACh lo4 M or BK. We conclude that EDRF is produced in the guinea pig pulmonary artery and descending aorta at birth and that EDRF is a mediator of the vasodilator actions of ACh and BK. Vasodilation by ACh may also involve activation of the cyclooxygenase pathway. (Pediatr Res 27: 128-132,1990) Abbreviations EDRF, endothelium-derived relaxing factor ACh, acetylcholine BK, bradykinin EDRF, now believed to be nitric oxide or a compound that releases nitric oxide, was discovered in 1980 when acetycholine was found to relax preconstricted rabbit artery strips in vitro only if the luminal endothelial cell lining was intact (1). Subsequently, EDRF has been identified by bioassay techniques in pulmonary and systemic arteries of many mammalian species and substances other than ACh (e.g. BK and calcium ionophore) have been shown to stimulate EDRF production. Based on a rapidly expanding body of work (2) that followed the discovery of EDRF, certain bioassay criteria have evolved for attributing vasodilatation to EDRF. These include inhibition of vascular relaxation: 1 ) after removal of or injury to luminal endothelium of the blood vessel (1); 2) by pretreatment with methylene blue that inhibits the increase in cGMP in smooth muscle cells associated with EDRF production (3); and 3) by pretreatment with methemoglobin or Hb that binds EDRF (4).EDRF has not previously been described in pulmonary and systemic blood vessels at birth. It is known that ACh (5) and BK are potent dilators of the perinatal pulm...

Impaired Endothelial Function and Increased Carotid Stiffness in 9-Year-Old Children With Low Birthweight

“…In addition to its key role in vascular reactivity, experimental studies have shown that the endothelium may also be important for long-term arterial remodeling and in the control of elastic properties of the arterial wall. 31,32 Damage to the endothelium in large arteries has been shown not only to impair active diameter changes 33 but also to increase the viscosity of the arterial wall. 32 A total of 10 of 32 eligible LBW subjects were lost to follow-up.…”

Prostaglandin Inhibition Prevents the Fall in Pulmonary Vascular Resistance as a Result of Rhythmic Distension of the Lungs in Fetal Lambs

“…These other mechanisms most likely involve the vasodilator peptide, bradykinin, which is produced by the lungs during oxygenation (21). Bradykinin may exert its effect either directly or by stimulating endotheliumderived relaxing factor, a potent vasodilator (20) produced by the endothelium of pulmonary arteries of newborn guinea pigs (22). Although bradykinin effects also may be mediated by PGs (23), this specific mechanism is unlikely to be of major importance during the transitional period, based on the findings of this study.…”

“…The Society for Behavioral Pediatrics will conduct its 9th Annual Scientific Meeting and Workshops on September [21][22][23]1991 …”

Endothelium-Derived Relaxing Factor: Evidence That It Regulates Pulmonary Vascular Resistance in the Isolated Neonatal Guinea Pig Lung

“…from the pulmonary artery and descending aorta of 1-to 3-d-old guinea pigs. The dilator action of bradykinin on pulmonary artery rings in vitro was attributed primarily to EDRF (14). In the present study, we examined whether EDRF plays an important role in the neonatal lung microvasculature as a vasoactive substance that controls neonatal pulmonary vascular resistance.…”

“…A very recent report suggests that EDRF synthesis may contribute to the decrease of pulmonary vascular resistance that occurs at birth ( 13), but it is not known whether impaired EDRF activity is involved in the pulmonary hypertension associated with a variety of neonatal lung diseases, such as persistent pulmonary hypertension of the newborn and bronchopulmonary dysplasia. In previous work (14), we demonstrated the presence of EDRF in isolated vascular rings from the pulmonary artery and descending aorta of the newborn guinea pig. One finding was that in vitro, bradykinin, a putative mediator of the pulmonary hernodynamic adjustments at birth (l5), relaxed the preconstricted neonatal pulmonary artery ring by an EDRFdependent mechanism.…”