Mg. Clement et al., PROSTANOIDS COUNTERBALANCE THE BRONCHOCONSTRICTOR ACTIVITY OF ENDOTHELIN-1 IN PIGS, Prostaglandins, leukotrienes and essential fatty acids, 58(3), 1998, pp. 177-183
In 12 anaesthetized spontaneously breathing pigs divided into two grou
ps of six animals we evaluated the respiratory and haemodynamic respon
ses to endothelin-1 (ET-1) administered by aerosol (200 pmol.kg(-1) in
1 mi of saline solution). In the first group (control group), the res
ponses to ET-1 were evaluated before and after the blocking of endogen
ous nitric oxide (NO) by N-G-nitro-L-arginine methyl ester (L-NAME 5 m
g.kg(-1), i.v.). In the second group (indomethacin-pretreated group),
the experimental protocol was similar to that of the control group, bu
t the responses were evaluated after the blocking of endogenous prosta
noids by indomethacin (3 mg.kg(-1), i.v.). Results show that in the co
ntrol group ET-1 administered before and after L-NAME did not change c
ompliance (Crs) or resistances (Rrs) of the respiratory system. In ind
omethacin-pretreated pigs, ET-1 significantly increased Rrs and decrea
sed Crs. This constrictor effect appearing only during the block of ar
achidonic acid metabolites showed that ET-1 activity can be counterbal
anced by a release of dilator prostanoids. In this group after L-NAME
pretreatment ET-1 did not alter the mechanical properties of the respi
ratory system, suggesting an involvement of other bronchodilator mecha
nisms. In the control group, aerosol administered ET-1 increased mean
systemic (MAP) and pulmonary (MPAP) arterial pressures, while when ET-
1 was administered after L-NAME pretreatment, MPAP decreased. In the i
ndomethacin-pretreated group, the peptide did not modify MAP, but caus
ed an early decrease in MPAP when administered after L-NAME. Therefore
, our results show that ET-1 caused a bronchoconstrictor effect only i
n indomethacin-pretreated pigs and suggest that the intrinsic constric
tor activity of the peptide can be modulated especially by the release
of dilator prostanoids.