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Increased Ca2+ sensitivity as a key mechanism of PKC-induced constriction in pressurized cerebral arteries.
Gokina N, Knot H, Nelson MT, Osol G
American Journal of Physiology-Heart and Circulatory Physiology. 1999;277( 3 Pt 2):H1178-88.
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Abstract
The effects of activating protein kinase C (PKC) with indolactam V (Indo-V) and 1,2-dioctanoyl-sn-glycerol (DOG) on smooth muscle intracellular Ca2+ concentrations ([Ca2+]i) and arterial diameter were determined using ratiometric Ca2+ imaging and video edge detection of pressurized rat posterior cerebral arteries. Elevation of intraluminal pressure from 10 to 60 mmHg resulted in an increase in [Ca2+]i from 74 +/- 5 to 219 +/- 8 nM and myogenic constriction. Application of Indo-V (0.01-3 microM) or DOG (0.1-30 microM) induced constriction and decreased [Ca2+]i to 140 +/- 11 and 127 +/- 12 nM, respectively, at the highest concentrations used. In the presence of Indo-V, the dihydropyridine Ca2+-channel-blocker nisoldipine produced nearly maximum dilation and decreased [Ca2+]i to 97 +/- 7 nM. In alpha-toxin-permeabilized arteries, the constrictor effects of Indo-V and DOG were not observed in the absence of Ca2+. Both PKC activators significantly increased the degree of constriction of permeabilized arteries at different [Ca2+]i. We conclude that 1) Indo-V- or DOG-induced constriction of pressurized arteries requires Ca2+ influx through voltage-dependent Ca2+ channels, and 2) PKC-induced constriction of pressurized rat cerebral arteries is associated with a decrease in [Ca2+]i, suggesting an increase in the Ca2+ sensitivity of the contractile process.
Keyword(s)
Animals; Female; Male; Rats; Rats, Inbred WKY; drug effects: Enzyme Activation; drug effects: Vasoconstriction; pharmacology: Carcinogens; pharmacology: Diglycerides; pharmacology: Indoles; pharmacology: Lactams; physiology: Calcium; physiology: Cerebral Arteries; physiology: Muscle, Smooth, Vascular; physiology: Protein Kinase C