S. Kita et al., PLATELETS ENHANCE CONTRACTILITY IN PERFUSED RAT MESENTERIC-ARTERIES -INVOLVEMENT OF ENDOTHELIN-1, European journal of pharmacology, 340(2-3), 1997, pp. 209-215
We investigated the effects of platelet supernatant on presser respons
es to norepinephrine in isolated perfused rat mesenteric arteries. Per
fusion of the arteries with platelet supernatant for 2 h markedly enha
nced the presser responses to norepinephrine(10(-6) and 3 x 10(-6) M).
This enhancement was significantly inhibited by phosphoramidon(10(-4)
M), an endothelin converting enzyme inhibitor. Both BQ788 amma-D-1-me
thoxycarbonyltryptophanyl-D-norleucine] (10(-6) M), an endothelin ETB
receptor antagonist, and bosentan (Ro47-0203, tyl-N-[6-(2-hydroxy-etho
xy)-5-(benzenesulfonamide] (10(-5) M), a nonselective endothelin recep
tor antagonist, also prevented the potentiation of responses to norepi
nephrine evoked by platelet supernatant, but FR139317 ((R)2-[(R)-2-[(S
)-2-[[1 ro-1H-azepinyl)]carbonyl]amino-4-methyl-pentanoyl] (1-methyl-1
H-indoyl)]propionyl]amino-3-(2-pyridyl) propionic acid) (10(-6) M), an
endothelin ETA receptor antagonist, had little effect. Suppressor dos
es of endothelin-1 (3 X 10(-10) M) or sarafotoxin S6c (S6c) (3 x 10(-1
0) M) potentiated significantly the norepinephrine-induced vasoconstri
ction, in the same preparation. Moreover, supernatant-induced enhancem
ent of presser responses to norepinephrine was markedly suppressed by
TGF-beta 1 neutralizing antibody. Transforming growth factor-beta 1 (T
GF-beta 1) (40 pM) also significantly enhanced the presser responses t
o norepinephrine (10(-6) M) and this enhancement was significantly inh
ibited by phosphoramidon. These results suggest that platelet-derived
TGF-beta 1 stimulates the vascular production of endothelin-1 and ther
eby enhances vasoconstrictor responses to norepinephrine. Platelet-ind
uced enhancement of vasoconstrictor responses to norepinephrine seems
to be mainly mediated by endothelin ETB receptor, in rat mesenteric ar
teries. (C) 1997 Elsevier Science B.V.