F. Perez-vizcaino et al., Pulmonary artery vasoconstriction but not [Ca2(+)](i) signal stimulated bythromboxane A(2) is partially resistant to NO, PEDIAT RES, 50(4), 2001, pp. 508-514
To characterize the thromboxane A(2) (TXA(2))-induced resistance to the vas
odilator effects of the nitric oxide (NO)/cGMP pathway in pulmonary arterie
s, we have studied the effects of the NO donor sodium nitroprusside on intr
acellular calcium concentration ([Ca2+])(i) and contractile force recorded
simultaneously in isolated piglet pulmonary arteries loaded with fura-2 and
contracted with norepinephrine or the TXA(2) mimetic U46619 and by activat
ion of protein kinase C (PKC) with phorbol 12-myristate 13-acetate,. In the
TXA(2) mimetic- and phorbol 12-myristate 13-acetate plus norepinephrine-st
imulated arteries, nitroprusside, exhibited lower vasodilator efficacy (and
lower potency in the TXA(2) mimetic-stimulated arteries) but similar reduc
tions in [Ca2+](i) compared with arteries activated by norepinephrine. The
nonselective serine/threonine kinase inhibitor staurosporine, but not the s
elective inhibitor of PKC bisindolylmaleimide, potentiated the relaxation o
f nitroprusside in the TXA(2) mimetic-stimulated arteries. In conclusion, t
he resistance to NO/cGMP-induced vasodilation in arteries stimulated by TXA
(2) and PKC involves a reduced ability of the Ca2+-independent mechanisms f
or smooth muscle vasodilation. The resistance to NO in arteries stimulated
by TXA(2) is sensitive to staurosporine but not to bisindolylmaleimide, sug
gesting the involvement of an activation of a serine/threonine kinase disti
nct from PKC.