HETEROGENEITY IN ENDOTHELIUM-DERIVED NITRIC OXIDE-MEDIATED RELAXATIONOF DIFFERENT-SIZED PULMONARY-ARTERIES OF NEWBORN LAMBS

Endothelium-derived nitric oxide (EDNO) plays a pivotal role in regula ting pulmonary circulation. To determine whether there is a heterogene ity in EDNO-mediated responses of different sized pulmonary vessels, w e studied small and large isolated pulmonary arteries of newborn lambs (diameter, 0.4-0.7 and 1.5-2.5 mm, respectively). The isometric tensi on of vessel rings were recorded while suspended in organ chambers fil led with modified Krebs-Ringer bicarbonate solution (95% 0(2)-5% CO2, 37 degrees C), In vessels preconstricted with norepinephrine, acetylch oline and bradykinin induced a greater relaxation of small pulmonary a rteries than of large pulmonary arteries. Acetylcholine, bradykinin, a nd nitric oxide also induced a greater increase in cGMP content in sma ll arteries than in large ones. The responses to acetylcholine and bra dykinin were endothelium-dependent and inhibited by nitro-L-arginine, an inhibitor of nitric oxide synthase, In vessels without endothelium, the response to nitric oxide was inhibited by 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase. The a ctivity of soluble guanylyl cyclase of small arteries was greater than that of large arteries under basal conditions and after stimulation w ith S-nitroso-N-acetylpenicillamine, a nitric oxide donor. These resul ts demonstrate that heterogeneity exists in EDNO-mediated relaxation o f small and large pulmonary arteries in newborn lambs. A difference in the soluble guanylate cyclase activity of vascular smooth muscle may have contributed to this phenomenon.