Cc. Docherty et Mr. Maclean, ENDOTHELIN(B) RECEPTORS IN RABBIT PULMONARY RESISTANCE ARTERIES - EFFECT OF LEFT-VENTRICULAR DYSFUNCTION, The Journal of pharmacology and experimental therapeutics, 284(3), 1998, pp. 895-903
The endothelin (ET) receptor that mediates vasoconstriction of the iso
lated rabbit pulmonary resistance artery was characterized using selec
tive ET receptor agonists and antagonists. We also examined changes in
ET-induced vasoconstriction brought about by left ventricular dysfunc
tion using the rabbit coronary ligation model. The rank order of poten
cy for contraction was sarafotoxin S6c (S6c) > ET-1 = ET-3, which is c
haracteristic of an ETB-like receptor. The combined ETA/ETB receptor a
ntagonist SB209670 (1 mu M) antagonized responses to ET-1 and S6c with
estimated pK(b) values of 6.8 +/- 0.2 and 7.8 +/- 0.2, respectively.
BQ788 (1 mu M) antagonized responses to S6c and ET-3 (but not ET-1) wi
th estimated pK(b) values of 7.1 +/- 0.2 and 6.6 +/- 0.1, respectively
. The ETA receptor antagonist FR139317 (1 mu M), either alone or in co
mbination with BQ788, did not inhibit responses to ET-1. The profile o
f the ET-1 response was not altered by left ventricular dysfunction. I
n control rabbits, the inhibitor of nitric oxide synthase N-omega-nitr
o-L-arginine methyl ester (100 mu M) had no significant effect on the
potency of either ET-1 or S6c. In the coronary-ligated rabbits, howeve
r, it significantly increased the potency (10-15-fold) of both ET-1 an
d S6c. These results suggest that the ET receptor that mediates contra
ction in rabbit pulmonary resistance arteries has the characteristics
of an ETB-like receptor. The responses to ET-1 are not altered by LVD
but may be modified by increased release of nitric oxide.