D. Pape et al., Endothelin, but not angiotensin II, contributes to the hypoxic contractileresponse of large isolated pulmonary arteries in the rat, FUN CL PHAR, 13(4), 1999, pp. 461-467
4The aims of this study were to investigate whether angiotensin ii and/or e
ndothelin could contribute to the hypoxic contractile response of isolated
rat pulmonary artery. Experiments were performed for 1 h on noradrenaline p
recontracted arterial rings in hypoxic conditions (95% N-2 and 5% CO2). Nic
ardipine, lisinopril, losartan, phosphoramidon, FR139317 and bosentan were
used to block Ca2+ channels, angiotensin I-converting enzyme, AT(1) recepto
rs, endothelin-converting enzyme, ETA receptors, and ETA/ETB receptors, res
pectively. The profile of the hypoxic contractile response was biphasic, di
splaying, after a short relaxation: a weak and transient contraction (from
2-4 min) and then, before complete relaxation, a slowly developed but susta
ined contraction (from 14-60 min). Endothelium removal abolished the transi
ent contraction and reduced (-59%) the sustained contraction. Nicardipine d
id not modify the transient contraction, but consentration-dependently decr
eased (from -35% to -100%) the sustained contraction (P = 0.024). Lisinopri
l and losartan did not affect the response (P = 0.418 and P = 0.973, respec
tively). Bosentan did not modify the transient contraction, but concentrati
on-dependently decreased (from -14% to -71%) the sustained contraction (P =
0.016), whereas phosphoramidon and FR139317 did not affect the response (P
= 0.830 and P = 0.806, respectively). Conclusions: in rat. (i) both phases
of the hypoxic contractile response are endothelium-dependent and independ
ent of angiotensin II; (ii) the transient contraction does not depend on en
dothelin; (iii) the sustained contraction, which involves calcium influx, a
ppears partly dependent on mature endothelin released from storage granules
by stimulating ETB receptors.