Effects of staurosporine and calphostin C, two structurally unrelated inhibitors of protein kinase C, on vascular tone.

In isolated rings of the rabbit facial vein, facial artery, and aorta, calphostin C and staurosporine, inhibitors of protein kinase C, reduced myogenic tone and norepinephrine (1 microM), K+ (80 mM), and Ca2+ (1.6 mM) induced tone. In all instances, staurosporine was more potent than calphostin C. In contrast to staurosporine, the IC50 value of calphostin C against myogenic tone was similar to that recorded for protein kinase C in biochemical studies (0.086 vs. 0.050 microM) and the average IC50 values of calphostin C against norepinephrine (2.2 microM), K+ (3.3 microM), and Ca2+ (4.3 microM) in the three vessels were similar to that for myosin light-chain kinase in biochemical studies (> 5.0 microM). In the facial vein, calphostin C was 59-fold more potent against myogenic tone than against Ca(2+)-induced tone and 8-fold more specific for myogenic tone than was staurosporine. In addition, at concentrations not affecting K+ (80 mM) induced tone, calphostin C suppressed 1-oleoyl-2-acetyl-sn-glycerol induced tone in the facial vein, whereas staurosporine only attenuated it by 65%. Thus calphostin C inhibits protein kinase C dependent tone in isolated blood vessels to a greater extent than does staurosporine.