H(2)O(2) mediates Ca(2+)- and MLC(20) phosphorylation-independent contraction in intact and permeabilized vascular muscle.
One purpose of the current study was to establish whether vasoconstriction occurs in all vessel types in response to H(2)O(2). Isometric force was measured in pulmonary venous and arterial rings, and isobaric contractions were measured in mesenteric arteries and veins in response to H(2)O(2). A second purpose was to determine whether H(2)O(2)-induced contraction is calcium independent. The addition of H(2)O(2) to calcium-depleted (using the Ca(2+) ionophore ionomycin in zero calcium EGTA buffer) muscle caused contraction. Furthermore, permeabilized muscle contracted in response to H(2)O(2) even in zero Ca(2+). The final purpose was to determine whether the 20-kDa regulatory myosin light chain (MLC(20)) phosphorylation plays a role in H(2)O(2)-induced contraction. Pulmonary arterial strips were freeze-clamped at various time points during H(2)O(2)-induced contractions, and the relative amounts of phosphorylated MLC(20) were measured. H(2)O(2) caused dose-dependent contractions that were independent of MLC(20) phosphorylation. ML-9, a myosin light chain kinase inhibitor, had no effect on the H(2)O(2) contractile response. In conclusion, H(2)O(2) induces Ca(2+)- and MLC(20) phosphorylation-independent contraction in pulmonary and systemic arterial and venous smooth muscle.
Pelaez
N J
NJ
Departments of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis, Indiana 46202-5102, USA.
Braun
T R
TR
Paul
R J
RJ
Meiss
R A
RA
Packer
C S
CS
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014680:Veins / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; D007476:Ionophores; D018994:Myosin Light Chains; D011189:Potassium Chloride; D006861:Hydrogen Peroxide; D009219:Myosin-Light-Chain Kinase; D002118:Calcium; D009638:Norepinephrine