Heat-induced force suppression and HSP20 phosphorylation in swine carotid media.
In vascular smooth muscle, cyclic nucleotide-dependent phosphorylation of heat shock protein 20 (HSP20) on serine-16 (Ser16) has been suggested to cause force suppression, i.e., reduced force with only minimal myosin regulatory light chain (MRLC) dephosphorylation. We hypothesized that heat pretreatment also suppresses force by increasing HSP20 phosphorylation. After heat pretreatment of swine carotid artery at 44.5 degrees C for 4 h and reduction to 37 degrees C for 1 h, Ser16-HSP20 phosphorylation was increased and histamine-induced increases in contractile force were suppressed. Subsequent addition of nitroglycerin induced additive force suppression. Heat and nitroglycerin induced a similar relation between Ser16-HSP20 phosphorylation and force. Heat pretreatment induced a small, but significant, increase in total HSP20 immunostaining. These results demonstrate that vascular smooth muscle responds to thermal stress by increasing Ser16-HSP20 phosphorylation in addition to a possible small increase in total HSP20 concentration. The resulting heat-induced reduction in force should be considered "force suppression" because histamine-induced increases in MRLC phosphorylation were not significantly altered by heat pretreatment. These processes may bring about a resistance to contractile agonists, which could have clinical significance in conditions such as hyperthermia and/or sepsis with vasodilatory shock.
Cardiovascular Division, Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
Matthew J
MJ
O'Connor
Christopher M
CM
Rembold
D000818:Animals; D017536:Carotid Artery, Common / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D050886:HSP20 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006358:Hot Temperature; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D013552:Swine; D017540:Tunica Media / Q000378:metabolism
D050886:HSP20 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018994:Myosin Light Chains; D010750:Phosphoproteins; D009569:Nitric Oxide; D006632:Histamine; D006152:Cyclic GMP