EFFECTS OF STAUROSPORINE AND CALPHOSTIN-C, 2 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 muM), 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 muM) and the average IC50 values of calphostin C against norepinephrine (2.2 muM), K+ (3.3 muM), and Ca2+ (4.3 muM) in the three vessels were similar to that for myosin light-chain kinase in biochemical studies (>5.0 muM). In the facial vein, calphostin C was 59-fold more potent against myogenic tone than against Ca2+-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.