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.