Myogenic tone refers to the ability of vascular smooth muscle to alter its state of contractility in response to changes of intraluminal pressure; the vessel constricts in opposition to an increase in intravascular pressure and dilates when the pressure decreases. The mechanisms by which vascular smooth muscle cells respond to changes in intravascular pressure are still not well understood. In this study, we investigated the role of protein kinase C- or RhoA proteins-induced Ca2+ sensitization in myogenic tone of the rabbit basilar microcirculation by measuring Fura-2 Ca2+ signals, contractile responses, PKC immunoblots, translocation of the PKC and RhoA proteins, and phosphorylation of 20kDa myosin light chains.
Stretch evoked myogenic tone with increase in [Ca2+]i only in the presence of extracellular Ca2+. Stretch-induced increase in [Ca2+]i & contractions were completely abolished in the absence of extracellular Ca2+. Stretch-induced increase in [Ca2+]i & contractions were inhibited by treatment of tissue with nifedipine, blocker of voltage-dependent Ca2+ channel, but not in gadolinium, blocker of stretch-activated cation channel. PKC inhibitors, H-7 & calphostin C, and Rho-kinase inhibitor, Y-27632, inhibited a stretch-induced myogenic tone without changes in [Ca2+]i. Imunoblotting using isoenzyme-specific antibodies showed the presence of PKCα and PKCε in the rabbit basilar artery. PKCα, but not PKCε, and RhoA proteins were translocated from cytosol to the cell membrane by stretch. Phosphorylation of MLC20 was increased by stretch and these increases were blocked by treatment of tissue with H-7 & Y-27632.
These results suggest a link between the Ca2+ sensitization that occurs during the myogenic contraction and activation of the PKCα and RhoA proteins.
Source: Korean Journal of Physiology & Pharmacology.2000 Oct;4(Suppl):S13-S13
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