In hypertension, the kidney is not always the heart of the matter
J. Clin. Invest. Michael E. Mendelsohn, et al. 115:840 doi:10.1172/JCI24806 [Go to this article.]

Figure 2
Vascular tone is dynamically regulated by MLC phosphorylation and dephosphorylation in VSMCs. Increases in VSMC intracellular calcium level via receptor-activated (pharmacomechanical) or ion channel–activated (electromechanical) pathways lead to MLCK activation. MLCK phosphorylates MLCs (MLC-P), activating the myosin ATPase, actinomyosin cross-bridging, and an increase in tension. PP1M dephosphorylates MLC-P, decreasing cell tension. PP1M is activated by the NO and nitrovasodilator effector PKGI, which has 2 isoforms (PKGIα and PKGIβ). RGS2, which is essential for normal blood pressure, causes VSMC relaxation by attenuating Gq protein–coupled receptor activation and associated rises in intracellular calcium concentration; it too is activated by PKGIα. PP1M is inhibited by Rho/Rho kinase (ROCK). The calcium-activated potassium channel, BK_Ca2+, is activated by PKG and by local calcium sparks, hyperpolarizing the cell, decreasing calcium entry, and decreasing MLCK activity. This shifts the equilibrium between MLC and MLC-P, causing relaxation. Blue, relaxant pathway; red, contractile pathway. GPCR, G protein–coupled receptor; IP₃R, IP₃ receptor; SR, sarcoplasmic reticulum; PLC, phospholipase C; CaM, calmodulin; IRAG, IP₃R-associated cGMP kinase substrate.