Table 4.

VSMC contraction mechanisms and potential therapies for PH

Mechanism	Sources/Stimulators	Target	Potential Therapies for PH
[Ca2+]cyt	Ca2+ release from SR Ca2+ entry through channels	Ca2+/calmodulin, MLCK, MLC phosphorylation	Ca2+ channel blockers, Nifedipine
ROCK	Rho-A	Phosphorylates CPI-17, inhibits MLC phosphatase, ↑ Ca2+ sensitivity	ROCK inhibitors, Fasudil ROCK2 inhibitors, KD025
PKC	Diacylglycerol, Ca2+	Phosphorylates CPI-17, inhibits MLC phosphatase, ↑ Ca2+ sensitivity	PKC inhibitors, GF 109203X (Bisindolylmaleimide)

CPI-17, protein kinase C-potentiated phosphatase inhibitor protein-17; MLC, myosin light chain; MLCK, MLC kinase; PH, pulmonary hypertension; PKC, protein kinase C; ROCK, Rho-associated protein kinase; SR, sarcoplasmic reticulum.