The role of protein kinase C in thromboxane A(2)-induced pulmonary artery vasoconstriction

In order to determine if protein kinase C (PKC) plays a significant role in the stimulant action of thromboxane A(2) (TxA(2)) on pulmonary vascular sm ooth muscle, TxA(2)-induced contractile responses were measured following i nhibition of PKC, Rabbits were sacrificed and segments of the main trunk of the pulmonary artery were removed and placed with in a temperature-control led (37 degrees C) organ bath. Contractile responses that were evoked by a TxA2 mimetic (U46,619, 0.5 mu M) decreased by 27 and 35% following treatmen t with the PKC inhibitors, calphostin C (2 mu M) and staurosporine (200 nM) , respectively. These results account for the effect of the vehicle, DMSO, which was also found to have a concentration-dependent inhibitory effect on the U46,619-induced contractions. The effects of DMSO alone was subsequent ly subtracted from the previously measured responses to PKC inhibitors that were dissolved in DMSO to obtain effects attributable to the PKC inhibitor alone. It can therefore be concluded that inhibition of PKC results in par tial attenuation of U46,619-induced responses supporting the hypothesis tha t activation of PKC plays a partial role in TxA2-induced contraction of pul monary arterial smooth muscle.