Pulmonary artery vasoconstriction but not [Ca2(+)](i) signal stimulated bythromboxane A(2) is partially resistant to NO

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.