Effect of caspofungin is independent of protein kinase A (PKA) and guanylate cyclase reaction cascade. (A) The inhibition of PKA by application of H-89 (10 μM) significantly reduced the basal PTV. Administration of caspofungin in the presence of H-89 was immediately followed by a significant increase in the PTV. (B) The caspofungin-induced rapid increase in the PTV in the presence of H-89 was not different from the increase in the PTV evoked by caspofungin alone. (C) Inhibition of sGC using ODQ (10 μM) did not alter the PTV. Still, in the presence of ODQ, caspofungin application responded with a rapid and sustained increase in the PTV. (D) ODQ did not alter the PTV relative to control conditions. The response of the PTV to caspofungin in the presence of ODQ was higher than the response to caspofungin alone (caspo., caspofungin; horizontal bars in experimental recordings present exposure periods of defined pharmacological agents; n, number of individual experiments; ns, not significant; time scale bars are present in all individual panels; **, P < 0.01; ***, P < 0.001; Mann-Whitney U test).